Optimal pathway for treatIng neuropathic pain in diabetes mellitus (OPTION-DM)
| ISRCTN | ISRCTN17545443 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17545443 |
| EudraCT/CTIS number | 2016-003146-89 |
| Secondary identifying numbers | STH18976 |
- Submission date
- 09/09/2016
- Registration date
- 12/09/2016
- Last edited
- 20/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
The number of people with diabetes is growing rapidly in the UK and is predicted to increase from 3.2 million in 2013 to 5 million by 2025. People living with diabetes often have to live with long-term complications of the disease. One of these complications is diabetic peripheral neuropathy, where the nerves in the arms and legs become damaged, leading to painful symptoms. One quarter of all people with diabetes experience these symptoms, known as “painful diabetic neuropathy”. Patients may present with burning, aching or “electric-shock” type pains. In some patients normal touch by day time or bed clothes can cause severe pain as the skin becomes extremely sensitive to touch. As the pain is felt every day, patients may have difficulty doing simple daily activities such as walking to the shop or socializing with friends. This results in a poor quality of life and depression. Unfortunately current individual medications provide only partial benefit in around of half of all patients, with many enduring inadequate pain relief and unwanted reactions. Not surprisingly therefore, many patients are frustrated with not being able to work and too many visits to see the doctor. The negative impact on them, their families and the NHS is considerable. The National Institute for Heath and Care Excellence (NICE) recommends a choice of four drugs; amitriptyline, duloxetine, and pregabalin or gabapentin, as initial treatment for painful diabetic neuropathy. If the initial treatment is not fully effective NICE recommends adding one of the other drugs in combination with the first drug. The aim of this study is to find out which of these drugs is the most effective initial treatment and then the best additional treatment for patients with painful diabetic neuropathy.
Who can participate?
Adults with painful diabetic neuropathy
What does the study involve?
Participants are randomly allocated to receive the three treatment pathways in a different order. The first pathway involves taking amitriptyline for six weeks and then amitriptyline in combination with pregabalin for a further 10 weeks (if amitriptyline alone is not giving effective relief). The second pathway involves taking duloxetine for six weeks and then duloxetine in combination with pregabalin for a further 10 weeks (if necessary). The third pathway involves taking pregabalin for six weeks and then pregabalin in combination with amitriptyline for a further 10 weeks (if necessary). The total length of the study for each patient will be one year. During this period patients will be contacted by telephone and seen in hospital on multiple occasions. Study medications will be started at a low dose and increased gradually to find the right dose for each individual patient. Throughout the study, response to treatment will be measured using pain diaries which patients will be asked to complete. Participants also complete questionnaires at the start of the study and after 6 and 16 weeks of each treatment pathway the measure quality of life, mood, sleep and reactions to the drugs.
What are the possible benefits and risks of participating?
Possible benefits of the study are that participants will be contacted weekly by the study nurse during the study, and will be seen in clinic regularly, so are likely to have more follow-up than normal. Participants may also find a treatment pathway that is effective in treating their painful diabetic neuropathy. When the study is complete, participants will be advised which order they received the treatments, so that they are able to request their preferred treatment from their care team going forward. Possible risks are that participants will be required to stop all current pain medication before starting the study and between each pathway will need to stop taking the study medication. The amount of time without any treatment will be short but if concerns should be discussed with the study team. Also, taking part in this research may mean additional appointments at the hospital, compared to the number of appointments received normally. Although this means extra travel, travel costs in attending these hospital appointments will be reimbursed if required.
Where is the study run from?
12 hospital clinics and 80 GP practices across England (UK)
When is the study starting and how long is it expected to run for?
June 2016 to March 2021 (updated 13/04/2021, previously: January 2021)
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
1. Miss Jennifer Petrie (public)
j.petrie@sheffield.ac.uk
2. Professor Solomon Tesfaye (scientific)
solomon.tesfaye@nhs.net
Contact information
Public
Clinical Trials Research Unit, ScHARR
Regent Court
30 Regent Street
Sheffield
S1 4DA
United Kingdom
| Phone | +44 114 222 0676 |
|---|---|
| j.petrie@sheffield.ac.uk |
Scientific
Sheffield Teaching Hospitals and University of Sheffield
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom
 ORCID ID |
0000-0003-1190-1472 |
|---|---|
| Phone | +44 114 271 2204 |
| solomon.tesfaye@nhs.net |
Study information
| Study design | Multicentre double-blind centre-stratified multiperiod crossover trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | A multicentre, double-blind, centre-stratified multi-period crossover trial to evaluate the efficacy of the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus |
| Study acronym | OPTION-DM |
| Study hypothesis | Null hypothesis: There is no difference between the study Treatment Pathways (amitriptyline supplemented with pregabalin, duloxetine supplemented with pregabalin and pregabalin supplemented with amitriptyline). Alternative hypothesis: There is a true difference between the study Treatment Pathways (amitriptyline supplemented with pregabalin, duloxetine supplemented with pregabalin and pregabalin supplemented with amitriptyline). |
| Ethics approval(s) | Yorkshire and the Humber - Sheffield REC, 09/12/2016, ref: 16/YH/0459 |
| Condition | Painful diabetic neuropathy |
| Intervention | All participants will receive all 3 treatment pathways. A web-based randomisation system will determine the order in which they receive the pathways. Participants will be allocated to one of 6 sequences in an equal allocation to sequences (1:1:1:1:1:1). Treatment pathways: 1. Amitriptyline supplemented with pregabalin (if necessary) 2. Duloxetine supplemented with pregabalin (if necessary) 3. Pregabalin supplemented with amitriptyline (if necessary) Each treatment pathway has 2 treatment periods: 6 weeks monotherapy followed by 10 weeks combination therapy. Those patients who have adequate pain relief after 6 weeks will remain on monotherapy for the second treatment period. Each treatment pathway is preceded by a one week washout period. Each treatment pathway will last around 4 months and participants will receive treatment within the trial for around one year. There will be 3 dose levels for each drug. Participants will start on the lowest dose level of each drug and the dose will be titrated up to a maximum tolerated dose over the first 2 weeks of treatment. Blinding will be maintained with over-encapsulated drugs and matching placebo. The participants and the local research team will be blinded to treatment allocation with the exception of the site pharmacist who will be unblinded. Participants in all groups will be followed up after 6 and 16 weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | |
| Drug / device / biological / vaccine name(s) | Amitriptyline Duloextine Pregabalin |
| Primary outcome measure | Difference between 7 day average 24-hour pain evaluated at patient level using an 11 point NRS scale measured during the final follow-up week of each treatment pathway (Week 16) |
| Secondary outcome measures | Efficacy 1. Difference between 7-day average 24-hour pain (evaluated at patient level) on an 11 point NRS scale at Week 6 among monotherapies in each treatment pathway. 2. Health status is measured using RAND SF-36 physical mean scores at week 6 and 16 of each treatment pathway 3. Health status is measured using RAND SF-36 mental mean scores at week 6 and 16 of each treatment pathway 4. Proportion of patients having treatment success, defined as a reduction in 30% value at follow up compared to baseline, is measured by 7-day average 24-hour pain evaluated at patient level using an 11 point NRS scale at week 16 of each treatment pathway 5. Proportion of patients having treatment success, defined as a reduction in 50% value at follow up compared to baseline, is measured by 7-day average 24-hour pain evaluated at patient level using an 11 point NRS scale at week 16 of each treatment pathway 6. Pain interference with function total score is measured using the BPI-MSF at week 6 and 16 of each treatment pathway 7. Insomnia is measured using the Insomnia Severity Index at week 6 and 16 of each treatment pathway 8. Patient impression of change is measured using the Patient Global Impression of Improvement at week 16 of each treatment pathway 9. Care pathway preferred by participants is measured by patient interview at week 50 Cost Effectiveness 1. Cost Effectiveness is measured using the EuroQoL-5D-5L and a modified version of the Client Service Receipt Inventory (CSRI) at week 6 and week 16 of each treatment pathway Safety 1. Proportion of patients reporting at least one Adverse Event for each of the pathway is measured by patient interview at each study visit or telephone call. 2. Frequencies of Adverse Events for each of the pathway is measured bypatient interview at each study visit or telephone call. 3. Listing of Adverse Events for each of the pathway is measured by patient interview at each study visit or telephone call. 4. Proportion of patients reporting at least one Serious Adverse Event for each of the pathway is measured by patient interview at each study visit or telephone call. 5. Frequencies of Serious Adverse Events for each of the pathway is measured by patient interview at each study visit or telephone call. 6. Listing of Serious Adverse Events for each of the pathway is measured by patient interview at each study visit or telephone call. Subgroup analysis: All participants will complete the Neuropathic Pain Symptom Inventory (NPSI) questionnaire, which is used to categorise patients for subgroup analysis relating pain phenotype to treatment response. In particular these outcomes will be evaluated: 1. Difference between “Burning (superficial) spontaneous pain” NPSI mean subscores - (evaluated at patient level) at week 6 and week 16 among pathways 2. Difference between “Pressing (deep) spontaneous pain” NPSI mean subscores - (evaluated at patient level) at week 6 and week 16 among pathways 3. Difference between “Paroxysmal pain” NPSI mean subscores - (evaluated at patient level) at week 6 and week 16 among pathways 4. Difference between “Evoked pain” NPSI mean subscores - (evaluated at patient level) at week 6 and week 16 among pathways 5. Difference between “Paresthesia/dysesthesia” NPSI mean subscores - (evaluated at patient level) at week 6 and week 16 among pathways 6. Difference between NPSI mean total scores - (evaluated at patient level) at week 6 and week 16 among pathways Added 01/08/2017: 1. Difference between Hospital Anxiety and Depression Scale (HADS) mean anxiety scores (evaluated at patient level) at week 6 among pathways 2. Difference between Hospital Anxiety and Depression Scale (HADS) mean anxiety scores (evaluated at patient level) at week 16 among pathways 3. Difference between Hospital Anxiety and Depression Scale (HADS) mean depression scores (evaluated at patient level) at week 6 among pathways 4. Difference between Hospital Anxiety and Depression Scale (HADS) mean depression scores (evaluated at patient level) at week 16 among pathways Patient-perceived tolerability 1. Difference between tolerability (evaluated at patient level) on an 11-point NRS scale at week 16 among pathways 2. Difference between tolerability (evaluated at patient level) on an 11-point NRS scale at week 6 among monotherapies |
| Overall study start date | 01/06/2016 |
| Overall study end date | 24/03/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 392 |
| Total final enrolment | 140 |
| Participant inclusion criteria | Current inclusion criteria as of 29/01/2019: 1. Participant aged ≥18 years 2. Neuropathic pain affecting both feet and / or hands for at least 3 months or taking pain medication for neuropathic pain for at least 3 months 3. Bilateral distal symmetrical neuropathic pain confirmed by the Douleur Neuropathique 4 (DN4) questionnaire at screening visit (52). The participant is eligible if 4 or more questions are answered as “yes”. 4. Bilateral distal symmetrical polyneuropathy confirmed by modified Toronto Clinical Neuropathy Score (mTCNS) > 5 at screening visit (53) 5. Stable glycaemic control (HbA1c < 108mmol/mol) 6. Participants will have a mean total pain intensity of at least 4 on an 11-point numeric rating scale (NRS; with 0 being ‘no pain’ and 10 ‘worst pain imaginable’) during 1 week off pain medications (Baseline Period). Patients could be invited to attend Randomisation Visit sooner if it’s clear that their mean pain score for the week is above 4 i.e. as soon as the total sum of the pain scores is ≥ 28 (e.g. randomisation could take place after 3 days if a patient scores 10 on each of the first 3 days of monitoring). This is to minimise the length of time patients remain off neuropathic pain treatments. 7. Willing and able to comply with all the study requirements and be available for the duration of the study. This will be a 1 year study in which all participants will undergo all Treatment Pathways regardless of treatment response and this point will be made clear 8. Willing to discontinue current neuropathic pain relieving medications 9. Informed consent form for study participation signed by participant Previous inclusion criteria, as of 19/03/2018: 1. Aged 18 years and over 2. Neuropathic pain affecting both feet and / or hands for at least 3 months or taking pain medication for neuropathic pain for at least 3 months 3. Bilateral distal symmetrical polyneuropathy confirmed by modified Toronto Clinical Neuropathy Score (mTCNS) > 5 at screening visit 4. Bilateral distal symmetrical polyneuropathy confirmed by the Douleur Neuropathique 4 (DN4) questionnaire at screening visit 5. Stable glycaemic control (HbA1c < 108mmol/mol) 6. Participants will have a mean total pain intensity of at least 4 on an 11-point numeric rating scale (NRS; with 0 being ‘no pain’ and 10 ‘worst pain imaginable’) during 1 week off pain medications (Baseline Period) 7. Willing and able to comply with all the study requirements and be available for the duration of the study. This will be a 1 year study in which all participants will undergo all Treatment Pathways regardless of treatment response and this point will be made clear 8. Willing to discontinue current neuropathic pain relieving medications 9. Informed consent form for trial participation signed by participant Previous Inclusion Criteria: 1. Aged 18 years and over 2. Daily pain for at least 3 months or taking pain medication for neuropathic pain for at least 3 months 3. Bilateral distal symmetrical polyneuropathy confirmed by Michigan Neuropathy Screening Instrument (MNSI) score > 3 at screening visit 4. Bilateral distal symmetrical polyneuropathy confirmed by the Douleur Neuropathique 4 (DN4) questionnaire at screening visit 5. Stable glycaemic control (HbA1c < 108mmol/mol) 6. Participants will have a mean total pain intensity of at least 4 on an 11-point numeric rating scale (NRS; with 0 being ‘no pain’ and 10 ‘worst pain imaginable’) during 1 week off pain medications (Baseline Period) 7. Willing and able to comply with all the study requirements and be available for the duration of the study. This will be a 1 year study in which all participants will undergo all Treatment Pathways regardless of treatment response and this point will be made clear 8. Willing to discontinue current neuropathic pain relieving medications 9. Informed consent form for trial participation signed by participant |
| Participant exclusion criteria | Current exclusion criteria as of 25/02/2020: 1. Non-diabetic symmetrical polyneuropathies 2. History of alcohol/substance abuse which would, in the opinion of the investigator, impair their ability to take part in the study 3. History of severe psychiatric illnesses which would, in the opinion of the investigator, impair their ability to take part in the study 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breast feeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued with the exception of prior concomitant and safe use of selective serotonin reuptake inhibitors (SSRIs) with study medication (duloxetine and/or amitriptyline). Note that concomitant use of citalopram is not permitted 8. Use of high dose morphine equivalent (>100mg/day) 9. Liver disease (AST/ALT >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class III 12. Clinically significant cardiac arrhythmias on 12 lead ECG or current history of arrhythmia, second or third degree heart block or left bundle branch block (patients with right bundle branch block or first degree heart block may be included following discussion with cardiology team) 13. Patients with a recent myocardial infarction (<6 months prior to randomisation) 14. Symptomatic postural hypotension which in the opinion of the investigator is clinically significant and would be a contraindication to the study medication 15. Prostatic hypertrophy or urinary retention to an extent which would, in the opinion of the investigator, be a contraindication to the study medication 16. Patients with other painful medical conditions where the intensity of the pain is significantly more severe than their diabetic peripheral neuropathic pain (patients will not be excluded if the pain is transient in nature) 17. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 18. Significant language barriers which are likely to affect the participants understanding of the medication schedule or ability to complete outcome questionnaires 19. Concurrent participation in another clinical trial of an investigational medicinal product 20. Major amputations of the lower limbs 21. Foot ulcers, only if in the opinion of the local PI will have a confounding/detrimental effect on study primary outcome or participation e.g. localised foot pain from the ulcer site _____ Previous exclusion criteria as of 29/01/2019: 1. Non-diabetic symmetrical polyneuropathies 2. History of alcohol/substance abuse which would, in the opinion of the investigator, impair their ability to take part in the study 3. History of severe psychiatric illnesses which would, in the opinion of the investigator, impair their ability to take part in the study 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breast feeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued with the exception of prior concomitant and safe use of selective serotonin reuptake inhibitors (SSRIs) with study medication (duloxetine and/or amitriptyline) 8. Use of high dose morphine equivalent (>100mg/day) 9. Liver disease (AST/ALT >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class III 12. Clinically significant cardiac arrhythmias on 12 lead ECG or current history of arrhythmia 13. Patients with a recent myocardial infarction (<6 months prior to randomisation) 14. Symptomatic postural hypotension which in the opinion of the investigator is clinically significant and would be a contraindication to the study medication 15. Prostatic hypertrophy or urinary retention to an extent which would, in the opinion of the investigator, be a contraindication to the study medication 16. Patients with other painful medical conditions where the intensity of the pain is significantly more severe than their diabetic peripheral neuropathic pain (patients will not be excluded if the pain is transient in nature) 17. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 18. Significant language barriers which are likely to affect the participants understanding of the medication schedule or ability to complete outcome questionnaires 19. Concurrent participation in another clinical trial of an investigational medicinal product 20. Major amputations of the lower limbs 21. Foot ulcers, only if in the opinion of the local PI will have a confounding/detrimental effect on study primary outcome or participation e.g. localised foot pain from the ulcer site Previous exclusion criteria as of 06/09/2018: 1. Non-diabetic symmetrical polyneuropathies 2. History of alcohol/substance abuse which would, in the opinion of the investigator, impair their ability to take part in the study 3. History of severe psychiatric illnesses which would, in the opinion of the investigator, impair their ability to take part in the study 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breastfeeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued, with the exception of prior concomitant and safe use of selective serotonin reuptake inhibitors (SSRIs) with study medication (duloxetine and/or amitriptyline) 8. Use of high dose morphine equivalent (>100mg/day) 9. Liver disease (AST/ALT >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class II 12. Clinically significant cardiac arrhythmias on 12 lead ECG or current history of arrhythmia 13. Patients with a recent myocardial infarction (<6 months prior to randomisation) 14. Postural hypotension (reduction of > 20mmHg) 15. Prostatic hypertrophy or urinary retention to an extent which would, in the opinion of the investigator, be a contraindication to the study medication 16. Patients with other painful medical conditions where the intensity of the pain is significantly more severe than their diabetic peripheral neuropathic pain (patients will not be excluded if the pain is transient in nature) 17. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 18. Significant language barriers which are likely to affect the participants understanding of the medication schedule or ability to complete outcome questionnaires 19. Concurrent participation in another clinical trial of an investigational medicinal product 20. Major amputations of the lower limbs 21. Foot ulcers, only if in the opinion of the local PI will have a confounding/detrimental effect on study primary outcome or participation e.g. localised foot pain from the ulcer site Previous exclusion criteria, as of 19/03/2018: Exclusion Criteria: 1. Non-diabetic symmetrical polyneuropathies 2. History of alcohol/substance abuse which would, in the opinion of the investigator, impair their ability to take part in the study 3. History of severe psychiatric illnesses which would, in the opinion of the investigator, impair their ability to take part in the study 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breastfeeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued 8. Use of high dose morphine equivalent (>100mg/day) 9. Liver disease (AST/ALT >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class II 12. Clinically significant cardiac arrhythmias on 12 lead ECG or current history of arrhythmia 13. Patients with a recent myocardial infarction (<6 months prior to randomisation) 14. Postural hypotension (reduction of > 20mmHg) 15. Prostatic hypertrophy or urinary retention to an extent which would, in the opinion of the investigator, be a contraindication to the study medication 16. Patients with other painful medical conditions where the intensity of the pain is significantly more severe than their diabetic peripheral neuropathic pain (patients will not be excluded if the pain is transient in nature) 17. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 18. Significant language barriers which are likely to affect the participants understanding of the medication schedule or ability to complete outcome questionnaires 19. Concurrent participation in another clinical trial of an investigational medicinal product 20. Major amputations of the lower limbs 21. Active diabetic foot ulcers Previous exclusion criteria as of 19/03/2018 (added 01/08/2017): 1. Non-diabetic neuropathies 2. History of alcohol/substance abuse which would, in the opinion of the investigator, impair their ability to take part in the study 3. History of severe psychiatric illnesses which would, in the opinion of the investigator, impair their ability to take part in the study 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breastfeeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued 8. Use of high dose morphine equivalent (>100mg/day) 9. Liver disease (LFTs >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class II 12. Clinically significant cardiac arrhythmias on 12 lead ECG 13. Patients with a recent myocardial infarction (<6 months prior to randomisation) 14. Postural hypotension (reduction of > 20mmHg) 15. Prostatic hypertrophy or urinary retention to an extent which would, in the opinion of the investigator, be a contraindication to the study medication 16. Patients with other painful medical conditions where the intensity of the pain is significantly more severe than their diabetic peripheral neuropathic pain (patients will not be excluded if the pain is transient in nature) 17. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 18. Significant language barriers which are likely to affect the participants understanding of the medication schedule or ability to complete outcome questionnaires 19. Concurrent participation in another clinical trial of an investigational medicinal product 20. Major amputations of the lower limbs 21. Active diabetic foot ulcers Previous exclusion criteria, as of 01/08/2017: 1. Non-diabetic neuropathies 2. History of alcohol/substance abuse 3. History of severe psychiatric illnesses 4. History of epilepsy 5. Contraindications to study medications 6. Pregnancy/breastfeeding or planning pregnancy during the course of the study 7. Use of prohibited concomitant treatment (as detailed in section 8.10) that could not be discontinued 8. Use of high dose morphine equivalent (>120mg/day) 9. Liver disease (LFTs >2 times upper limit of normal) 10. Significant renal impairment (eGFR <30mL/minute/1.73m2) 11. Heart failure New York Heart Association (NYHA) ≥ class II 12. Clinically significant cardiac arrhythmias on 12 lead ECG 13. Prior history of ischaemic heart disease 14. Postural hypotension (reduction of > 20mmHg) 15. Prostatic hypertrophy or urinary retention 16. Any suicide risk as judged by the investigator or as defined by a score of ≥2 on the suicide risk questionnaire 17. Significant language barriers which are likely to affect the participant's understanding of the medication schedule or ability to complete outcome questionnaires |
| Recruitment start date | 02/11/2017 |
| Recruitment end date | 31/07/2019 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Glossop Road
Sheffield
S10 2JF
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Ashton-under-Lyne
OL6 9RW
United Kingdom
Ipswich
IP4 5PD
United Kingdom
London
SE5 9RS
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Birmingham
B9 5SS
United Kingdom
Chester
CH2 1UL
United Kingdom
Harrogate
HG2 7SX
United Kingdom
Liverpool
L9 7AL
United Kingdom
Sceptre Way
Walton Summit
Preston
PR5 6AQ
United Kingdom
Liverpool
L7 8XP
United Kingdom
DD1 9SY
United Kingdom
East Kilbride
Glasgow
G75 8RG
United Kingdom
Airdrie
ML6 0JS
United Kingdom
Heath Town
Wolverhampton
WV10 0QP
United Kingdom
Gateshead
NE9 6SX
United Kingdom
Morriston
Swansea
SA6 6NL
United Kingdom
Sponsor information
Hospital/treatment centre
Clinical Research Office
D Floor
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
England
United Kingdom
"ROR" |
https://ror.org/018hjpz25 |
|---|
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
Results and Publications
| Intention to publish date | 24/03/2022 |
|---|---|
| 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 | Planned publication in a high-impact peer-reviewed journal in early 2022. |
| 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 | protocol | 22/10/2018 | 11/01/2021 | Yes | No |
| Basic results | 23/03/2022 | 23/03/2022 | No | No | |
| Results article | 22/08/2022 | 26/08/2022 | Yes | No | |
| Results article | 01/10/2022 | 20/10/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
20/10/2022: Publication reference added.
26/08/2022: Publication reference added.
23/03/2022: The following changes have been made:
1. The basic results of this trial have been uploaded as an additional file.
2. The total final enrolment number has been changed from 139 to 140.
01/02/2022: Contact details updated.
10/01/2022: The intention to publish date was changed from 31/01/2022 to 24/03/2022.
13/04/2021: The overall end date was changed from 30/04/2021 to 24/03/2021.
11/01/2021: The following changes were made to the trial record:
1. The overall end date was changed from 31/01/2021 to 30/04/2021.
2. Publication reference added.
25/02/2020: The exclusion criteria were changed.
07/08/2019: Total final enrolment number added.
10/04/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 28/02/2019 to 31/07/2019.
2. The overall trial end date was changed from 31/08/2020 to 31/01/2021.
3. The intention to publish date was changed from 31/08/2021 to 31/01/2022.
31/10/2019: The plain English summary was updated.
29/01/2019: The following changes were made to the trial record:
1. The trial participating centres were updated.
2. The participant inclusion criteria was updated.
3. The participant exclusion criteria was updated.
12/12/2018: The following changes have been made:
1. The recruitment end date has been updated from 01/11/2018 to 28/02/2019.
2. The overall trial end date has been updated from 31/08/2019 to 31/08/2020.
3. The intention to publish date has been updated from 31/03/2020 to 31/08/2021.
06/09/2018: The following changes have been made to the trial record:
1. The participant exclusion criteria have been updated
2. The recruitment start date has been changed from 15/08/2017 to 02/11/2017
3. The recruitment end date has been changed from 14/08/2018 to 01/11/2018
4. Lancashire Care NHS Foundation Trust, Royal Liverpool and Broadgreen University Hospitals NHS Trust and Tayside Health Board have been added as trial participating centres
19/03/2018: Updated inclusion and exclusion criteria. Harrogate and District NHS Foundation Trust (UK) and Aintree University Hospitals NHS Foundation Trust (UK) were added as trial participating centres.
04/09/2017: The scientific title has been updated from "A multicentre, double-blind, centre-stratified multi-period crossover trial with a 6 month internal pilot to evaluate the efficacy of the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus" to "A multicentre, double-blind, centre-stratified multi-period crossover trial to evaluate the efficacy of the Optimal Pathway for TreatIng neurOpathic paiN in Diabetes Mellitus"
01/08/2017: The following changes were made to the trial record:
1. The secondary outcome measures and exclusion criteria were updated.
2. The recruitment start date was changed from 01/03/2017 to 15/08/2017.
3. The recruitment end date was changed from 28/02/2018 to 14/08/2018.
4. The trial participating centres were updated.
5. Ethics approval details added.
6. IPD sharing statement added.
