Optimal pathway for treatIng neuropathic pain in diabetes mellitus (OPTION-DM)
- Conditions
- Painful diabetic neuropathyNervous System Diseases
- Registration Number
- ISRCTN17545443
- Brief Summary
2018 Protocol article in https://pubmed.ncbi.nlm.nih.gov/30348206/ protocol (added 11/01/2021) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36007534/ (added 26/08/2022) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/36259684/ (added 20/10/2022)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 140
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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
Name Time Method