OPTION-DM
Research type
Research Study
Full 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 (OPTION-DM).
IRAS ID
213518
Contact name
Solomon Tesfaye
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2016-003146-89
ISRCTN Number
ISRCTN17545443
Duration of Study in the UK
1 years, 11 months, 28 days
Research summary
Research Summary
The number of people with diabetes is growing rapidly. Unfortunately diabetes causes nerve damage leading to severe pain in the feet, legs and hands, known as “painful diabetic neuropathy”. This pain is often felt every day, making simple daily activities such as walking or socializing difficult, resulting in poor quality of life and depression. Current individual medications provide only partial benefit to some patients, with many experiencing unwanted reactions, causing a negative impact on patients, families and the NHS.
The National Institute for Heath and Care Excellence (NICE) recommends amitriptyline, duloxetine, pregabalin or gabapentin, as initial treatment for painful diabetic neuropathy. If this is not effective, adding one of the other drugs in combination with the first is recommended. However, these individual drugs haven’t been systematically compared against each other to see which is best.
This study aims to find out the most effective initial treatment, and combination treatment for patients with painful diabetic neuropathy. This will improve patient care and quality of life, and benefit doctors and the NHS, as improved pain management reduces GP and hospital visits.
The study compares 3 treatment pathways using amitriptyline, duloxetine and pregabalin and their combinations, and 392 patients will take part. Patients will be allocated to one pathway starting with amitriptyline, duloxetine or pregabalin for 6 weeks and, if required, another drug added for a further 10 weeks. Each patient will go through all three pathways, and participation will last one year. Patients will be contacted regularly. Study medications will be started at a low dose and increased gradually to the right dose for each patient. Throughout the study, response to treatment will be measured, and quality of life measures, mood, sleep, and reactions to the drugs will be recorded. The value for money of each treatment pathway will also be measured.
Summary of Results
The number of people with diabetes is growing rapidly in the UK and is predicted to rise to over 5 million by 2025. Diabetes causes nerve damage that can lead to severe painful symptoms in the feet, legs and hands. One quarter of all people with diabetes experience these symptoms, known as “painful diabetic neuropathy”. Current individual medications provide only partial benefit in around half of patients. The individual drugs, and their combinations, have not been compared directly against each other to see which is best.
We conducted a study to see which Treatment Pathway would be best for patients with painful diabetic neuropathy. The study included three Treatment Pathways using combinations of amitriptyline, duloxetine and pregabalin. Patients received all three Treatment Pathways (amitriptyline treatment for six weeks and pregabalin added if needed for a further ten weeks, duloxetine treatment for six weeks and pregabalin added if needed for a further ten weeks and pregabalin treatment for six weeks and amitriptyline added if needed for a further ten weeks) but the order of the Treatment Pathways was decided at random. We compared the level of pain that participants experienced in each Treatment Pathway to see which worked best.
On average, people said their pain was similar after each of the three treatments and their combinations. However, two treatments in combination helped some patients with additional pain relief if they only partially responded to one. People also reported improved quality of life and sleep with the treatments, but these were similar for all the treatments. In the health economic analysis, the value for money and quality of life were similar for each pathway. This resulted in uncertainty in the cost-effectiveness conclusions with no-one pathway being more cost-effective than the others. The treatments had different side effects however: pregabalin appeared to make more people feel dizzy, duloxetine made more people nauseous, and amitriptyline resulted in more people having dry mouth. The pregabalin supplemented by amitriptyline pathway had the least number of treatment discontinuations due to side effects and may be the safest for patients.
REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
16/YH/0459
Date of REC Opinion
14 Nov 2016
REC opinion
Favourable Opinion