Painful diabetic neuropathy Nervous System Diseases Painful diabetic neuropathy
Conditions
Interventions
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 sequenc
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 3 at screening visit
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 bypa | — |
Countries
England, Scotland, United Kingdom, Wales
Contacts
Public ContactJennifer Petrie
Outcome results
None listed