Pramipexole trial for bipolar depression
| ISRCTN | ISRCTN72151939 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72151939 |
| EudraCT/CTIS number | 2018-002869-18 |
| IRAS number | 239794 |
| Secondary identifying numbers | 39561, IRAS 239794 |
- Submission date
- 19/08/2019
- Registration date
- 28/08/2019
- Last edited
- 29/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Background and study aims
The aim of this study is to find out whether pramipexole, co-prescribed with a mood stabiliser (lithium, valproate, carbamazepine and/or lamotrigine), is an efficient treatment for treatment-resistant bipolar depression.
Who can participate?
Patients aged 18 or over with treatment-resistant bipolar depression
What does the study involve?
If participants are on an antipsychotic it is gradually withdrawn, as it may block the effect of pramipexole. Additionally, if participants are not on a ‘mood stabiliser’, one is started. Once this is done, participants are randomly allocated to receive either pramipexole or placebo (dummy drug), in addition to an ongoing mood stabiliser. The trial team, participants and their treating mental health team do not know whether the participant receives pramipexole or placebo. The effectiveness of pramipexole after 12 weeks is assessed, and participants continue to be monitored by trial researchers for 48 weeks, even if they discontinue the initial treatment, giving real-life information on the use of this treatment. The effect on depressive symptoms and quality of life are assessed, along with side-effects and whether any other treatments are needed. Assessments are self-reported using an online system completed by participants, who are supported by email prompts. These methods have worked well in previous studies and participants approve of their use. The system allows more frequent (weekly) self-ratings of bipolar depression symptoms and thus gives a more complete picture of long-term symptom control. Paper versions are provided where necessary. Participants are telephoned monthly to assess other medication use and side effects.
What are the possible benefits and risks of participating?
Possible risks include adverse effects of pramipexole and/or carbamazepine, lamotrigine, lithium and/or valproate, distress from stopping their usual medication and/or starting a new medication, intrusion and/or inconvenience and/or change to lifestyle of completing online or paper questionnaires, weekly, and taking part in telephone calls with Research Assistants (RAs) and home visits by Clinical Studies Officers or similar. The mitigations to these risks include increased monitoring of the participants than would normally be conducted as part of standard care, including additional support from a wider team (local research team, clinical treating team if separate and RAs). For the participants’ convenience and to reduce burden, the study visits can be conducted in the clinic or in their own home, based on their preference. The eligibility criteria for the trial have been carefully considered to ensure that patients that are suitable to take part can be identified. Additionally, safety will be closely monitored and all participants will be given a safety card to keep on them at all times. This card will include details of the CNTW (Sponsor) out of hours service, which will be available for emergency clinical queries. Participants will also be provided with a participant diary, which will used as an aid to the participant to ensure that they take their medication correctly according to the schedule. Participants will also receive a personalised medication schedule with each prescription, to help with the changes to the medication dose across different periods of the study. The medication labels have been designed so that they are different colours for the two different strengths of tablets, which are also different shapes. This has been incorporated in the patient diary with colour coding and pictures.
Where is the study run from?
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
September 2019 to March 2023
Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC) (UK)
Who is the main contact?
1. Zoë Walmsley (public)
PAX.BD@newcastle.ac.uk
2. Andrew Swain (public)
PAX.BD@newcastle.ac.uk
3. Nicola Goudie (public)
PAX.BD@newcastle.ac.uk
Contact information
Ms Zoë Walmsley
Public
Public
Trial Manager
Newcastle Clinical Trials Unit
Newcastle University
1-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
| PAX.BD@newcastle.ac.uk |
Ms Nicola Goudie
Public
Public
Trial Manager
Newcastle Clinical Trials Unit
Newcastle University
1-4 Claremont Terrace
Newcastle upon Tyne
NE2 4AE
United Kingdom
 ORCID ID |
0000-0003-1211-936X |
|---|---|
| PAX.BD@newcastle.ac.uk |
Mr Andrew Swain
Public
Public
Trial Manager
Newcastle Clinical Trials Unit
1-4 Claremont Terrace
Newcastle University
Newcastle upon Tyne
NE2 4AE
United Kingdom
| PAX.BD@newcastle.ac.uk |
Study information
| Study design | Randomised; Both; Design type: Treatment, Drug, Health Economic |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A randomised, double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression |
| Study acronym | PAX-BD |
| Study hypothesis | The PAX-BD trial is a multi-centre, randomised, controlled trial of pramipexole versus placebo, and will elicit whether pramipexole, co-prescribed with a mood stabiliser (lithium, valproate, carbamazepine and/or lamotrigine), is an efficient treatment for treatment-resistant bipolar depression. |
| Ethics approval(s) | Approved 04/09/2019, North East - Newcastle & North Tyneside 2 Research Ethics Committee (NHS BT Blood Donor Centre, Holland Drive, Newcastle upon Tyne, Tyne and Wear, NE2 4NQ, UK; Tel: +44 (0)207 1048091; Email: nrescommittee.northeast-newcastleandnorthtyneside2@nhs.net), REC ref: 19/NE/0233 |
| Condition | Treatment-resistant bipolar depression |
| Intervention | Current interventions as of 29/07/2022: The pre-randomisation phase will allow patients to have their antipsychotics adjusted and mood stabiliser initiated if necessary. Once this is done, 290 participants will be randomly allocated in a 1:1 ratio to receive either pramipexole or placebo, in addition to an ongoing mood stabiliser. Randomisations will be carried out by a delegated and trained member of the research team at each site using the Sealed Envelope system (a central, secure, 24-hour web-based randomisation system with concealed allocation). The trial team, participants and their treating mental health team will not know whether the participant receives pramipexole or placebo; the trial is ‘double-blind’. For all participants, initiation of trial treatment will follow a 4-week titration schedule starting at 0.25 mg/day in a single (oral) dose usually at night for 3 days. Thereafter the dose will be increased by 0.25 mg/day every 3 days. The target dose will be 2.5 mg/day but titration will be based on tolerability and response. The dose attained at the end of Week 4 is then continued throughout weeks 5-12. Then from weeks 13- 48 pramipexole will be flexibly dosed between 0.25 and 2.5mg/day, determined by response and tolerability. During the flexible dosing stage of the study, decisions around medication dose alterations will be based on weekly mood scores (QIDS-SR and ASRM) and scores from the side effect items of the TSQM administered 4-weekly. Patient’s mood and response and tolerability will be categorised every 4 weeks. Participants will be provided with medication via 7 separate dispensing at specified timepoints during the study – as part of the last dispensing participants will be provided with enough medication to last them up until week 52 to ensure they have enough to taper down slowly (if this is required) as pramipexole should not be stopped suddenly The effectiveness of pramipexole after 12 weeks will be assessed, and participants will continue to be monitored by trial researchers for 48 weeks, even if they discontinue the initial treatment, giving real-life information on the use of this treatment. The effect on depressive symptoms and quality of life will be assessed, along with side-effects and whether any other treatments are needed. Assessments will be self-reported using an online system completed by participants, who will be supported by email prompts. These methods have worked well in previous studies and participants approve of their use. The system allows more frequent (weekly) self-ratings of bipolar depression symptoms and thus gives a more complete picture of long-term symptom control. Where necessary paper versions will be provided. Participants will be telephoned monthly to assess concomitant medication use and side-effects. _____ Previous interventions: In the pre-randomisation stage, if participants are on an antipsychotic it will be gradually withdrawn, as it may block the effect of pramipexole. Additionally, if participants are not on a ‘mood stabiliser’, one will be started. Once this is done, 290 participants will be randomly allocated in a 1:1 ratio to receive either pramipexole or placebo, in addition to an ongoing mood stabiliser. Randomisations will be carried out by a delegated and trained member of the research team at each site using the Sealed Envelope system (a central, secure, 24-hour web-based randomisation system with concealed allocation). The trial team, participants and their treating mental health team will not know whether the participant receives pramipexole or placebo; the trial is ‘double-blind’. For all participants, initiation of trial treatment will follow a 4-week titration schedule starting at 0.25 mg/day in a single (oral) dose usually at night for 3 days. Thereafter the dose will be increased by 0.25 mg/day every 3 days. The target dose will be 2.5 mg/day but titration will be based on tolerability and response. The dose attained at the end of Week 4 is then continued throughout weeks 5-12. Then from weeks 13- 48 pramipexole will be flexibly dosed between 0.25 and 2.5mg/day, determined by response and tolerability. During the flexible dosing stage of the study, decisions around medication dose alterations will be based on weekly mood scores (QIDS-SR and ASRM) and scores from the side effect items of the TSQM administered 4-weekly. Patient’s mood and response and tolerability will be categorised every 4 weeks. Participants will be provided with medication via 7 separate dispensing at specified timepoints during the study – as part of the last dispensing participants will be provided with enough medication to last them up until week 52 to ensure they have enough to taper down slowly (if this is required) as pramipexole should not be stopped suddenly The effectiveness of pramipexole after 12 weeks will be assessed, and participants will continue to be monitored by trial researchers for 48 weeks, even if they discontinue the initial treatment, giving real-life information on the use of this treatment. The effect on depressive symptoms and quality of life will be assessed, along with side-effects and whether any other treatments are needed. Assessments will be self-reported using an online system completed by participants, who will be supported by email prompts. These methods have worked well in previous studies and participants approve of their use. The system allows more frequent (weekly) self-ratings of bipolar depression symptoms and thus gives a more complete picture of long-term symptom control. Where necessary paper versions will be provided. Participants will be telephoned monthly to assess concomitant medication use and side-effects. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Pramipexole |
| Primary outcome measure | Depression symptoms measured using QIDS-SR questionnaire (Quick Inventory of Depressive Symptomatology) at 12 weeks |
| Secondary outcome measures | Current secondary outcome measures as of 12/10/2020: 1. Mood and anxiety symptoms over 48 weeks, and pleasure symptoms over 12 weeks, measured using the QIDS-SR questionnaire weekly to week 48, the Generalised Anxiety Disorder 7 (GAD-7) weekly to week 48 and the Snaith Hamilton Pleasure Scale (SHAPS) at weeks 0, 6 and 12 2. Psychosocial function measured using the Work and Social Adjustment Scale (WSAS) at weeks 0, 6, 12, 24, 36 and 48 3. Tolerability of pramipexole assessed using rates of AEs, SAEs and SUSARs reported describing severity, seriousness, causality and expectedness 4. Risk of switching to mania and occurrence of psychosis or impulse control disorders, which are known possible side-effects of pramipexole, measured using the Altman Self Rating Scale of Mania (ASRM) questionnaire completed weekly to week 48 5. Rates of impulsivity during treatment with pramipexole, measured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease – Rating Scale (QUIP-RS) at weeks 0, 6, 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) 6. Side effects and overall acceptability of pramipexole treatment measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) at Weeks 6, 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) and collection of Adverse Events - reported weekly to week 12 and then 4-weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) 7. Adherence to medication to which patients are randomised via participant reported dose taken during RA phone calls and from central trial medication accountability and reconciliation records 8. Quality of life assessed using EuroQoL 5 Dimension 5 Level (EQ-5D-5L) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 9. Capability assessed using the ICEpop CAPability measure for Adults (ICECAP-A) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 10. Capability in people with mental health problems assessed using the Oxford CAPabilities questionnaire-Mental Health (OxCAP-MH) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 11. Societal cost assessed uising the Health Economics Questionnaire (HEQ) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 12. Mania and depression assessed using Young Mania Self-Rating Scale (YMRS) at weeks 0 and 12, Montgomery Asberg Depression Rating Scale (MADRS) at weeks 0 and 12 and Quick Inventory of Depressive Symptomatology – Clinician Rated (QIDS-C) at weeks 0 and 12 _____ Previous secondary outcome measures: 1. Mood and anxiety symptoms over 48 weeks, and pleasure symptoms over 12 weeks, measured using the QIDS-SR questionnaire weekly to week 48, the Generalised Anxiety Disorder 7 (GAD-7) weekly to week 48 and the Snaith Hamilton Pleasure Scale (SHAPS) at week 0, 6 and 12 2. Psychosocial function measured using the Work and Social Adjustment Scale (WSAS) at weeks 0, 6, 12, 24, 36 and 48 3. Cardiovascular side effects of pramipexole via pulse and blood pressure measurements taken at weeks 0, 2, 6, 12, 24, 36 and 48 4. Risk of switching to mania and occurrence of psychosis or impulse control disorders, which are known possible side-effects of pramipexole, measured using the Altman Self Rating Scale of Mania (ASRM) questionnaire completed weekly to week 48 5. Rates of impulsivity during treatment with pramipexole, measured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease – Rating Scale (QUIP-RS) at weeks 0, 6, 12 and then 4 weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) 6. Side effects and overall acceptability of pramipexole treatment measured using the Treatment Satisfaction Questionnaire for Medication (TSQM) at Weeks 6, 12 and then 4 weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48) and collection of Adverse Events - reported weekly to week 12 and then 4 weekly to week 48 (weeks 16, 20, 24, 28, 32, 36, 40, 44 and 48 7. Adherence to medication to which patients are randomised via participant reported dose taken during RA phone calls and from central trial medication accountability and reconciliation records 8. Quality of life, wellbeing, health and social care and broader societal costs of patients randomised to either pramipexole or placebo. The incremental cost-effectiveness of pramipexole in comparison to placebo over 48 weeks measured using EuroQoL 5 Dimension 5 Level (EQ-5D-5L) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48, ICEpop CAPability measure for Adults (ICECAP-A) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48, Oxford CAPabilities questionnaire-Mental Health (OxCAP-MH) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 and the Health Economics Questionnaire (HEQ) at start of pre-randomisation and weeks 0, 6, 12, 24, 36 and 48 9. Mania and depression assessed using Young Mania Self-Rating Scale (YMRS) at weeks 0 and 12, Montgomery Asberg Depression Rating Scale (MADRS) at weeks 0 and 12 and Quick Inventory of Depressive Symptomatology – Clinician Rated (QIDS-C) at weeks 0 and 12 |
| Overall study start date | 25/04/2018 |
| Overall study end date | 01/03/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 290; UK Sample Size: 290 |
| Total final enrolment | 90 |
| Participant inclusion criteria | Current inclusion criteria as of 29/07/2022: Stage 1/ pre-randomisation: 1. Currently under the care of secondary care mental health services at screening with a plan for the patient to remain in secondary care throughout the period of the trial 2. A decision made by the patient’s clinical team that a change in medication is indicated 3. A current diagnosis of Bipolar Disorder (type I or II), defined as in DSM-5, which is supported by the use of the Mini-International Neuropsychiatric Interview (MINI) 4. Currently depressed, i.e. meeting DSM-5 criteria for a Major Depressive Episode assessed via MINI and with a current QIDS-SR >10 5. Current episode of depression failed to have responded to adequate trials, or lack of tolerability or patient declined/clinically inappropriate, of two different NICE recommended medications (quetiapine, olanzapine (with or without fluoxetine), lamotrigine) or lurasidone. Adequacy of treatment trial defined using a custom-designed 'Bipolar Demographics and Treatment Questionnaire' (BDTQ). 6. Aged 18 years or over at the point of consent 7. Willing and able to provide written informed consent prior to any trial procedures taking place 8. In the opinion of the investigator, is able to follow the trial prescription instructions and is able to manage 8 weeks supply of trial medication without risk of overdose 9. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)] 10. Women of child-bearing potential are required to use a highly effective contraceptive method during the pre-randomisation and post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) Stage 2/ at randomisation: 1. Been in Stage 1 (pre-randomisation) for a minimum of 23 calendar days. 2. Currently depressed, i.e. meeting DSM-5 (78) criteria for a Major Depressive Episode and with a current QIDS-SR >10. 3. A minimum of two telephone/teleconference or videoconference calls with a trial RA and two on-line weekly symptom ratings have been completed during the pre-randomisation phase 4. On mood stabilising medication (lithium, valproate, carbamazepine, lamotrigine) 5. If on an antipsychotic this must be one listed, and at a dose of no more than the maximum stated, in the table in section 4.1. 6. All regular psychotropic medication, including antipsychotics and mood stabilisers, at a stable dose for a minimum of four weeks. Additionally, if a participant is on lamotrigine, quetiapine, olanzapine or lurasidone then this must have been at the current dose or higher for a minimum of three months. 7. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)]*. 8. Women of child-bearing potential are required to use a highly effective contraceptive method during the post-randomisation phase of the trial. Highly effective methods of contraception include: 8.1. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 8.2. progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 8.3. intrauterine device (IUD) 8.4. intrauterine hormone-releasing system (IUS) 8.5. vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) 8.6. bilateral tubal occlusion 8.7. sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) 9. Willing and able to confirm written informed consent at the point of randomisation, after the pre-randomisation period. _____ Previous inclusion criteria as of 12/10/2020: Stage 1/ pre-randomisation: 1. Currently under the care of secondary care mental health services at screening with a plan for the patient to remain in secondary care throughout the period of the trial 2. A decision made by the patient’s clinical team that a change in medication is indicated 3. A current diagnosis of Bipolar Disorder (type I or II), defined as in DSM-5, which is supported by the use of the Mini-International Neuropsychiatric Interview (MINI) 4. Currently depressed, i.e. meeting DSM-5 criteria for a Major Depressive Episode assessed via MINI and with a current QIDS-SR >10 5. Current episode of depression failed to have responded to adequate trials, or lack of tolerability or patient declined/clinically inappropriate, of two different NICE recommended medications (quetiapine, olanzapine (with or without fluoxetine), lamotrigine) or lurasidone. Adequacy of treatment trial defined using a custom-designed 'Bipolar Demographics and Treatment Questionnaire' (BDTQ). 6. Aged 18 years or over at the point of consent 7. Willing and able to provide written informed consent prior to any trial procedures taking place 8. In the opinion of the investigator, is able to follow the trial prescription instructions and is able to manage 8 weeks supply of trial medication without risk of overdose 9. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)] 10. Women of child-bearing potential are required to use a highly effective contraceptive method during the pre-randomisation and post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) Stage 2/ at randomisation: 1. Currently depressed, i.e. meeting DSM-5 (56) criteria for a Major Depressive Episode and with a current QIDS-SR >10. 2. A minimum of two telephone phone calls with a trial RA and two on-line weekly symptom ratings have been completed during the pre-randomisation phase 3. On mood stabilising medication (lithium, valproate, carbamazepine, lamotrigine) 4. All regular psychotropic medication, including mood stabilisers, at a stable dose for a minimum of four weeks 5. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)]. 6. Women of child-bearing potential are required to use a highly effective contraceptive method during the post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) 7. Willing and able to confirm written informed consent at the point of randomisation, after the pre-randomisation period. _____ Previous inclusion criteria as of 20/05/2020: Stage 1/ pre-randomisation: 1. Currently under the care of secondary care mental health services at screening with a plan for the patient to remain in secondary care throughout the period of the trial. 2. A decision made by the patient’s clinical team that a change in medication is indicated. 3. A current diagnosis of Bipolar Disorder (type I or II), defined as in DSM-5, which is supported by the use of the Mini-International Neuropsychiatric Interview (MINI) (55). 4. Currently depressed, i.e. meeting DSM-5 criteria for a Major Depressive Episode assessed via MINI and with a current QIDS-SR >10. 5. Current episode of depression failed to have responded to adequate trials, or lack of tolerability or patient declined/clinically inappropriate, of two different NICE recommended medications (quetiapine, olanzapine + fluoxetine, lamotrigine) or lurasidone. Adequacy of treatment trial defined using a custom designed ‘Bipolar Demographics and Treatment Questionnaire’ (BDTQ). 6. Aged 18 or over at the point of consent. 7. Willing and able to provide written informed consent prior to any trial procedures taking place. 8. In the opinion of the investigator, is able to follow the trial prescription instructions and is able to manage 8 weeks supply of trial medication without risk of overdose. 9. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)]. 10. Women of child-bearing potential are required to use a highly effective contraceptive method during the pre-randomisation and post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) Stage 2/ at randomisation: 1. Currently depressed, i.e. meeting DSM-5 (56) criteria for a Major Depressive Episode and with a current QIDS-SR >10. 2. A minimum of two telephone phone calls with a trial RA and two on-line weekly symptom ratings have been completed during the pre-randomisation phase 3. On mood stabilising medication (lithium, valproate, carbamazepine, lamotrigine) 4. All regular psychotropic medication, including mood stabilisers, at a stable dose for a minimum of four weeks 5. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)]. 6. Women of child-bearing potential are required to use a highly effective contraceptive method during the post-randomisation phase of the trial. Highly effective methods of contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) - progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) - bilateral tubal occlusion - sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) 7. Willing and able to confirm written informed consent at the point of randomisation, after the pre-randomisation period. _____ Previous inclusion criteria: Stage 1/ pre-randomisation: 1. Currently under the care of secondary care mental health services at screening with a plan for the patient to remain in secondary care throughout the period of the trial 2. A decision made by the patient’s clinical team that a change in medication is indicated 3. A current diagnosis of Bipolar Disorder (type I or II), defined as in DSM-5, which is supported by the use of the Mini-International Neuropsychiatric Interview (MINI) 4. Currently depressed, i.e. meeting DSM-5 criteria for a Major Depressive Episode assessed via MINI and with a current QIDS-SR > 10 5. Current episode of depression failed to have responded to adequate trials, or lack of tolerability or patient refusal, of two different NICE recommended medications (quetiapine, olanzapine + fluoxetine, lamotrigine) or lurasidone. Adequacy of treatment trial defined using a custom designed ‘Bipolar Depression Treatment Questionnaire’ (BDTQ) 6. Aged 18 or over at the point of consent 7. Willing and able to provide written informed consent prior to any trial procedures taking place 8. In the opinion of the investigator, is able to follow the trial prescription instructions and is able to manage 8 weeks supply of trial medication without risk of overdose 9. The patient, if female and of child-bearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG)] 10. Women of child-bearing potential are required to use a highly effective contraceptive method during the pre-randomisation and post-randomisation phase of the trial. Highly effective methods of contraception include: 10.1 Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 10.2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 10.3. Intrauterine device (IUD) 10.4 Intrauterine hormone-releasing system (IUS) 10.5. Vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) 10.6. Bilateral tubal occlusion 10.7. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) Stage 2/ at randomisation: 1. Currently depressed, i.e. meeting DSM-5 (53) criteria for a Major Depressive Episode and with a current QIDS-SR > 10 2. A minimum of two telephone phone calls with a trial RA and two on-line weekly symptom ratings have been completed during the pre-randomisation phase 3. On mood stabilising medication (lithium, valproate, carbamazepine, lamotrigine) 4. All regular psychotropic medication, including mood stabilisers, at a stable dose for a minimum of four weeks 5. The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin (β-hCG) 6. Women of child-bearing potential are required to use a highly effective contraceptive method during the post-randomisation phase of the trial. Highly effective methods of contraception include: 6.1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) 6.2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) 6.3. Intrauterine device (IUD) 6.4. Intrauterine hormone-releasing system (IUS) 6.5. Vasectomised partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success) 6.6. Bilateral tubal occlusion 6.7. Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject) 7. Willing and able to confirm written informed consent at the point of randomisation, after the pre-randomisation period Qualitative interviews A sample of participants who opt to consent to qualitative interviews will be contacted. For staff interviews, a sample of PIs at sites that have been open to recruitment for at least 4 months, and are willing to be interviewed, will be contacted. |
| Participant exclusion criteria | Current exclusion criteria as of 29/07/2022: Stage 1/ pre-randomisation: 1. DSM-5 defined severe substance use disorder. 2. Current psychotic symptoms as assessed using the MINI. 3. History of retinal disease. 4. Current cardiovascular symptoms or significant concerns around cardiovascular disease. 5. History of significant renal disease (for example within the last 6 months eGFR is less than 50ml/min/1.73m2 or there is a concern that eGFR is deteriorating and may be expected to fall below 50 during the course of the study). 6. Any known sensitivity to trial drug including its excipients. 7. Current pregnancy or planned pregnancy during the trial period, or breastfeeding. 8. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 9. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 10. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 11. Significant clinical concern regarding impulse control behaviours Stage 2/ at randomisation: 1. Psychotic symptoms over the preceding 4 weeks. 2. Any known sensitivity to trial drug including its excipients 3. Any deterioration in physical or mental health since pre-randomisation that means there is a clinical concern to proceed with the study. 4. Current or planned pregnancy during the trial period, or breast feeding. 5. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 6. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 7. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 8. Significant clinical concern regarding impulse control behaviours 9. Electroconvulsive therapy (ECT) in the last 28 days. 10. Any study team’s concern regarding the patient’s ability to remain engaged in the study collecting self-ratings of their symptoms and undertake all study procedures. _____ Previous exclusion criteria as of 20/05/2020: Stage 1/ pre-randomisation: 1. DSM-5 defined severe substance use disorder. 2. Current psychotic symptoms as assessed using the MINI. 3. History of retinal disease. 4. Current cardiovascular symptoms or significant concerns around cardiovascular disease. 5. History of significant renal disease (for example within the last 6 months eGFR is less than 50ml/min/1.73m2 or there is a concern that eGFR is deteriorating and may be expected to fall below 50 during the course of the study). 6. Any known sensitivity to trial drug including its excipients. 7. Current pregnancy or planned pregnancy during the trial period, or breastfeeding. 8. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 9. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 10. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 11. Significant clinical concern regarding impulse control behaviours Stage 2/ at randomisation: 1. Psychotic symptoms over the preceding 4 weeks. 2. Any known sensitivity to trial drug including its excipients 3. Any deterioration in physical or mental health since pre-randomisation that means there is a clinical concern to proceed with the study. 4. On an antipsychotic at the point of randomisation. 5. Current or planned pregnancy during the trial period, or breast feeding. 6. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation. 7. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt). 8. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome (where restless legs syndrome has been formally diagnosed by a sleep clinic). 9. Significant clinical concern regarding impulse control behaviours 10. Any study team’s concern regarding the patient’s ability to remain engaged in the study collecting self-ratings of their symptoms. _____ Previous exclusion criteria: Stage 1/ pre-randomisation: 1. DSM-5 defined severe substance use disorder 2. Current psychotic symptoms as assessed using the MINI 3. History of retinal disease 4. Current cardiovascular symptoms or significant concerns around cardiovascular disease 5. History of renal disease 6. Any known sensitivity to trial drug including its excipients 7. Current pregnancy or planned pregnancy during the trial period, or breastfeeding 8. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation 9. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt) 10. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome 11. Clinical concern of previous impulse control behaviours including harmful alcohol or drug use, binge eating, gambling or sexual behaviours, or regarding significant suicidal risks Stage 2/ at randomisation: 1. Psychotic symptoms over the preceding 4 weeks 2. Any known sensitivity to trial drug including its excipients 3. Any deterioration in physical or mental health since pre-randomisation that means there is a clinical concern to proceed with the study 4. On an antipsychotic at the point of randomisation 5. Current or planned pregnancy during the trial period, or breastfeeding 6. Starting specific psychotherapy from four weeks before randomisation through to Week 12 post-randomisation 7. Currently taking part in another clinical trial that would interfere with the outcomes of PAX-BD (site team to check with the CI and Trial Management Group if in doubt) 8. Confirmed diagnosis with potential confounding factors such as Parkinson’s disease, restless leg syndrome 9. Clinical concern of previous impulse control behaviours including harmful alcohol or drug use, binge eating, gambling or sexual behaviours or regarding significant suicidal risks 10. Any study team’s concern regarding the patient’s ability to remain engaged in the study collecting self-ratings of their symptoms |
| Recruitment start date | 30/09/2019 |
| Recruitment end date | 14/06/2022 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust
St. Nicholas Hospital
Jubilee Road
Gosforth
Newcastle Upon Tyne
NE3 3XT
United Kingdom
Jubilee Road
Gosforth
Newcastle Upon Tyne
NE3 3XT
United Kingdom
Nottinghamshire Healthcare NHS Foundation Trust
The Resource, Trust HQ
Duncan Macmillan House
Porchester Road
Nottingham
NG3 6AA
United Kingdom
Duncan Macmillan House
Porchester Road
Nottingham
NG3 6AA
United Kingdom
Surrey and Borders Partnership NHS Foundation Trust
18 Mole Business Park
Randalls Road
Leatherhead
KT22 7AD
United Kingdom
Randalls Road
Leatherhead
KT22 7AD
United Kingdom
Avon And Wiltshire Mental Health Partnership NHS Trust
Jenner House
Avon Way
Langley Park
Chippenham
SN15 1GG
United Kingdom
Avon Way
Langley Park
Chippenham
SN15 1GG
United Kingdom
Derbyshire Healthcare NHS Foundation Trust
Trust Headquarters
Kingsway Hospital
Kingsway
Derby
DE22 3LZ
United Kingdom
Kingsway Hospital
Kingsway
Derby
DE22 3LZ
United Kingdom
Oxford Health NHS Foundation Trust
Warneford Hospital
Warneford Lane
Headington
Oxford
OX3 7JX
United Kingdom
Warneford Lane
Headington
Oxford
OX3 7JX
United Kingdom
Cheshire and Wirral Partnership NHS Foundation Trust
Trust Board Offices
Upton Lea Resource Centre
The Countess Of Chester Health Park
Chester
CH2 1BQ
United Kingdom
Upton Lea Resource Centre
The Countess Of Chester Health Park
Chester
CH2 1BQ
United Kingdom
Devon Partnership NHS Trust
Wonford House Hospital
Dryden Road
Exeter
EX2 5AF
United Kingdom
Dryden Road
Exeter
EX2 5AF
United Kingdom
Leicestershire Partnership NHS Trust
Riverside House
Bridge Park Plaza
Bridge Park Road
Thurmaston
Leicester
LE4 8PQ
United Kingdom
Bridge Park Plaza
Bridge Park Road
Thurmaston
Leicester
LE4 8PQ
United Kingdom
Lincolnshire Partnership NHS Foundation Trust
Unit's 8 & 9
The Point
Lions Way
Sleaford
NG34 8GG
United Kingdom
The Point
Lions Way
Sleaford
NG34 8GG
United Kingdom
South West Yorkshire Partnership NHS Foundation Trust
Trust Headquarters
Fieldhead
Ouchthorpe Lane
Wakefield
WF1 3SP
United Kingdom
Fieldhead
Ouchthorpe Lane
Wakefield
WF1 3SP
United Kingdom
Sheffield Health & Social Care NHS Foundation Trust
Fulwood House
Old Fulwood Road
Sheffield
S10 3TH
United Kingdom
Old Fulwood Road
Sheffield
S10 3TH
United Kingdom
South London and Maudsley NHS Foundation Trust
Maudsley Hospital
Denmark Hill
London
SE5 8AZ
United Kingdom
Denmark Hill
London
SE5 8AZ
United Kingdom
Essex Partnership University NHS Foundation Trust
The Lodge
Runwell Chase
Runwell
Wickford
SS11 7XX
United Kingdom
Runwell Chase
Runwell
Wickford
SS11 7XX
United Kingdom
NHS Tayside
Ninewells Hospital and Medical School
James Arrott Drive
Dundee
DD1 9SY
United Kingdom
James Arrott Drive
Dundee
DD1 9SY
United Kingdom
NHS Lothian
Waverley Gate
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
NHS Greater Glasgow and Clyde
J B Russell House
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Gartnavel Royal Hospital
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Tees, Esk and Wear Valleys NHS Foundation Trust
West Park Hospital
Darlington
DL2 2TS
United Kingdom
Darlington
DL2 2TS
United Kingdom
Lancashire & South Cumbria NHS Foundation Trust
Unit 5
Sceptre Point
Sceptre Way
Preston
PR5 6AW
United Kingdom
Sceptre Point
Sceptre Way
Preston
PR5 6AW
United Kingdom
Kent and Medway NHS and Social Care Partnership Trust
Canada House
Barnsole Road
Gillingham
ME7 4JL
United Kingdom
Barnsole Road
Gillingham
ME7 4JL
United Kingdom
Sponsor information
Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
c/o Ms Lyndsey Dixon
St Nicholas Hospital
Jubilee Road
Gosforth
Newcastle Upon Tyne
NE3 3XT
England
United Kingdom
| Phone | +44 (0)191 246 7222 |
|---|---|
| NTWSponsorManagement@ntw.nhs.uk | |
| Website | http://www.ntw.nhs.uk/ |
"ROR" |
https://ror.org/01ajv0n48 |
Funders
Funder type
Government
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/154/01
No information available
Results and Publications
| Intention to publish date | 01/09/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. The protocol is not yet published – the SAP is not yet available 2. Peer reviewed scientific journals 3. Conference presentation 4. Publication on website 5. Other publication 6. Submission to regulatory authorities |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 05/07/2021 | 07/07/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | version 01 | 11/01/2024 | 26/07/2024 | No | Yes |
| Results article | 01/02/2025 | 29/04/2025 | Yes | No |
Additional files
Editorial Notes
29/04/2025: Publication reference added.
26/07/2024: The lay summary of results was uploaded.
27/03/2023: Total final enrolment added.
27/10/2022: The intention to publish date was changed from 31/10/2022 to 01/09/2023.
29/07/2022: The following changes were made to the trial record:
1. The interventions were changed.
2. The inclusion criteria were changed.
3. The exclusion criteria were changed.
4. The recruitment end date was changed from 31/03/2021 to 14/06/2022.
5. The trial participating centres Somerset Partnership NHS Foundation Trust, Coventry and Warwickshire Partnership NHS Trust, North East London NHS Foundation Trust, South West London and St George's Mental Health NHS Trust, Norfolk And Suffolk NHS Foundation Trust, Camden and Islington NHS Foundation Trust were removed.
31/05/2022: The study contacts have been updated and the plain English summary has been updated to reflect this change.
12/10/2021: The following changes have been made:
1. The recruitment end date has been changed from 29/09/2021 to 31/03/2022.
2. The overall trial end date has been changed from 31/10/2021 to 01/03/2023.
3. The study contacts have been updated.
4. The plain English summary has been updated to reflect the changes above.
07/07/2021: Publication reference added.
12/10/2020: The following changes have been made:
1. Recruitment has resumed.
2. Two public contacts have been added.
3. The trial website has been updated.
4. The secondary outcome measures have been changed.
5. The participant inclusion criteria have been changed.
20/05/2020: The following changes were made to the trial record:
1. The trial participating centre Bradford District Care NHS Foundation Trust was removed.
2. The inclusion criteria were changed.
3. The exclusion criteria were changed.
4. The sponsor name was changed from "Northumberland, Tyne and Wear NHS Foundation Trust" to "Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust"
20/04/2020: Due to current public health guidance, recruitment for this study has been paused.
21/02/2020: The following changes have been made:1. The trial participating centres "North East London NHS Foundation Trust" and "Coventry and Warwickshire Partnership NHS Trust" have been added and the plain English summary has been updated to reflect this change.
2. The IRAS number has been added.
17/02/2020: The name of the trial participating centre "Northumberland, Tyne and Wear NHS Foundation Trust" was changed to "Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust", and "Lancashire Care NHS Foundation Trust" was changed to "Lancashire & South Cumbria NHS Foundation Trust".
19/11/2019: The trial participating centres were updated to remove Dudley And Walsall Mental Health Partnership NHS Trust and Northern Heath & Social Care Trust and add Somerset Partnership NHS Foundation Trust.
18/11/2019: Ethics approval details added.
15/10/2019: Tees, Esk and Wear Valleys NHS Foundation Trust, Lancashire Care NHS Foundation Trust and Kent and Medway NHS and Social Care Partnership Trust were added to the trial participating centres.
11/10/2019: Rotherham Doncaster and South Humber NHS Foundation Trust, Berkshire Healthcare NHS Foundation Trust and Midlands Partnership NHS Foundation Trust were removed from the trial participating centres.
19/08/2019: Trial's existence confirmed by the NIHR.
