Can losartan enhance the effects of cognitive behavioural therapy in the treatment of panic disorder?
| ISRCTN | ISRCTN94854860 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN94854860 |
| EudraCT/CTIS number | 2015-003542-68 |
| Secondary identifying numbers | 20285 |
- Submission date
- 03/02/2016
- Registration date
- 03/02/2016
- Last edited
- 27/03/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English Summary
Background and study aims
Anxiety disorders are a group of common disorders in which a person experiences overwhelming and often disabling anxiety. It is thought to affect at least one in five people at some point in their lives, and can involve insecurity in social situations, worrying excessively, or having unexpected panic attacks. Panic disorder is a serious condition where the sufferers experiences sudden periods of extreme fear with no prior warming, in the form of a severe panic attack. Cognitive behavioural therapy (CBT) is a type of talking therapy which works by changing the way that people think and behave. It can be very effective in treating people suffering from anxiety disorders however courses are often time-consuming, expensive and difficult to access. A recent study has shown that just one session of CBT can dramatically improve anxiety symptoms. This is thought to be because the therapy actually changes the way that the brain processes threatening information that could lead to a panic attack (emotional processing). Very early on in treatment, patients already process information in a more positive way, and such early changes are related to how well the patient responds to treatment in the longer term. Treatments which boost these early effects of emotional processing may therefore improve the effectiveness of CBT in the treatment for panic disorder. Losartan is a drug commonly used to treat high blood pressure, as it improves blood flow by preventing blood vessels from narrowing. Animal studies have shown this drug can also help stimulate the part of the brain which plays a role in the ability to make new connections and retain information. The aim of this study is to find out whether a single dose of losartan could help to amplify the effects of a single session of CBT in the treatment of panic disorder, leading to an improvement in emotional processing.
Who can participate?
Adults suffering from panic disorder.
What does the study involve?
Participants are randomly allocated to one of two study groups. Both groups receive a single session of cognitive behavioural therapy (CBT) which lasts for around one hour. Those in the first group are given a single dose of 50mg losartan one hour before the therapy session. Those in the second group are given an identical looking placebo (dummy) capsule at the same timepoint. At the start of the study and then again one day later, participants in both groups have their emotional processing measured using simple computer tasks and an MRI (brain scan). The participants also have their anxiety levels measured at these times as well as one and six months later to see if the treatment has made any difference.
What are the possible benefits and risks of participating?
Participants may benefit from a reduction in their anxiety levels following the treatment. Risks of taking part are small as there are no reported side-effects for the dose of losartan used in this study. There is a small risk that some participants may find the experience of having an MRI scan to be uncomfortable and may feel claustrophobic (fear of confined spaces).
Where is the study run from?
Warneford Hospital, University Department of Psychiatry (UK)
When is the study starting and how long is it expected to run for?
February 2016 to March 2023
Who is funding the study?
1. National Institute for Health Research (UK)
2. MQ: Transforming Mental health (UK)
Who is the main contact?
Dr Andrea Reinecke
andrea.reinecke@psych.ox.ac.uk
Contact information
Public
Warneford Hospital
University Department of Psychiatry
Warneford Lane
Headington
Oxford
OX3 7JX
United Kingdom
| Phone | +44 1865 226471 |
|---|---|
| andrea.reinecke@psych.ox.ac.uk |
Study information
| Study design | Randomized double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Laboratory, University/medical school/dental school, Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | The effect of single-dose losartan on the basic effects of cognitive behavioural therapy for panic disorder -A randomized double-blind placebo-controlled trial |
| Study hypothesis | Losartan versus placebo augmented cognitive-behaviour therapy: 1. Will lead to greater reduction in threat bias on the day after treatment 2. Will lead to better clinical outcome at 1-month follow-up. |
| Ethics approval(s) | South Central - Oxford A Research Ethics Committee, 28/01/2016, ref: 15/SC/0648 |
| Condition | Panic disorder |
| Intervention | Patients will be randomised to a group receiving losartan or placebo, with the participant and experimenter remaining blind to group allocation throughout the study. Blocked randomisation will be used where patients are allocated to sequential numbers while stratifying for gender and panic diagnosis (with agoraphobia/ without agoraphobia). Both groups will receive a single session of cognitive behavioural therapy (CBT), lasting for around 60 minutes, with the losartan group receiving a single dose of 50mg losartan 1 hour before CBT, and the placebo group receiving an identical-looking placebo capsule. Effects of treatment on emotional processing will be measured on the day after treatment, clinical symptom severity will be measured one day, one month, and six months post-treatment. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Losartan |
| Primary outcome measure | Symptom severity is measured using the clinician-rated questionnaires Panic Disorder Severity Scale and Clinical Global Impression Scale at baseline, one month and six months post-treatment, as well as the self-report questionnaires State-Trait Anxiety Inventory, Beck Depression Inventory, Panic Attack Scale, Agoraphobic Cognitions Questionnaire, Body Sensations Questionnaire, Mobility Inventory, Visual Analogue Scales during Stress at baseline, one day, one month and six months post-treatment. |
| Secondary outcome measures | Emotion processing is measured using behavioural reaction time tasks at baseline and one day post treatment, as well as using a functional MRI one day post treatment. |
| Overall study start date | 06/10/2015 |
| Overall study end date | 31/03/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 40; UK Sample Size: 40; Description: 20 participants will receive the active drug losartan, 20 participants will receive placebo in combination with single-session CBT. The allocation will be randomised. |
| Total final enrolment | 40 |
| Participant inclusion criteria | 1. Participant is willing and able to give informed consent for participation in the study and to comply with all study requirements 2. Aged 18 years or above 3. Diagnosed with DSMIV panic disorder 4. At least moderate avoidance of agoraphobic situations *Participants with MRI contraindications (e.g. pacemaker, metal implant, left-handedness) can be included in the study but will not undergo the MRI scan study component. |
| Participant exclusion criteria | 1. Female participant who is pregnant or breastfeeding 2. CNS-active medication during the last 6 weeks 3. Current blood pressure or other heart medication (especially aliskiren or beta blockers) 4. Intravascular fluid depletion 5. Impaired liver or kidney function 6. Lifetime history of epilepsy or other neurological disease, systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study 7. Lifetime history of psychosis, bipolar disorder, alcohol, medication or drug abuse or dependence; current primary depressive disorder 8. Insufficient English skills 9. Participated in another study involving certain medication during the last 6 weeks 10. Patient unable to refrain from benzodiazepines 48 hours before treatment and testing sessions |
| Recruitment start date | 16/02/2016 |
| Recruitment end date | 31/12/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Warneford Lane
Headington
Oxford
OX3 7JX
United Kingdom
Sponsor information
University/education
Warneford Hospital
Department of Psychiatry
Warneford Lane
Headington
Oxford
OX3 7JX
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Results will be presented at a national and international conference once recruitment has closed, and will be published in peer-review journals. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
27/03/2023: The following changes have been made:
1. The study settings laboratory and university/medical school/dental school were added.
2. Total final enrolment was added.
3. The recruitment end date has been changed from 30/06/2021 to 31/12/2022.
4. The intention to publish date has been changed from 30/09/2023 to 31/12/2023.
14/12/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/12/2021 to 31/03/2023.
2. The intention to publish date was changed from 30/06/2022 to 30/09/2023.
3. The plain English summary was updated to reflect these changes.
21/09/2021: Internal review.
26/04/2021: The intention to publish date has been changed from 30/06/2020 to 30/06/2022.
02/04/2019: The condition has been changed from "Topic: Mental Health; Subtopic: Anxiety; Disease: Anxiety" to "Panic disorder" following a request from the NIHR.
26/03/2018: The recruitment end date was changed from 31/12/2021 to 30/06/2021.
23/03/2018: The overall trial end date was changed from 31/12/2019 to 31/12/2021.
22/03/2018: The recruitment end date was changed from 31/12/2018 to 31/12/2021.
17/03/2016: Verified study information with principal investigator.
