Authors' objectives: 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. Unfortunately diabetes causes nerve damage that causes severe painful symptoms in the feet, legs and hands. 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 cloths 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, 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. However, the NICE highlighted that: 1) these individual drugs haven t been compared against each other to see which one is the best and 2) the different combinations of these drugs have also not been compared against each other. In the proposed study we aim to find out the most effective initial treatment and then the best additional treatment for patients with painful diabetic neuropathy. This will improve patient care and quality of life. This will also benefit doctors treating patients with painful diabetic neuropathy and the NHS, as improved pain management reduces GP and hospital visits. This study will compare 3 treatment pathways using amitriptyline, duloxetine and pregabalin and their combinations. Gabapentin was excluded as: the evidence for gabapentin is only derived from one reasonable quality trial compared to 8 in pregabalin; gabapentin is a trice daily drug; and gabapentin, unlike pregabalin requires a long titration period to avoid toxicity. 392 patients from 8 hospitals clinics and 80 GP practices will be recruited. The investigators at each centre are specialists in diabetes and the treatment of painful diabetic neuropathy, and have experience in recruiting suitable patients for the study. Patients will be allocated to one of three treatment pathways starting with either amitriptyline, duloxetine or pregabalin for 6 weeks and for people still in pain, another drug added for a further 10 weeks. Each patient will go through all three treatment pathways. The total length of the study for each patient will be one year. During this period patients will be contacted by telephone or seen in hospital on 26 occasions. Study medications will be started at a low dose and increased gradually to the right dose for the patient. Throughout the study, response to treatment will be measured using pain diaries which patients will be asked to complete. We will also use measures of quality of life, mood, sleep and reactions to the drug, using special questionnaires. The value for money of each treatment pathway will also be measured. In summary, we hope this trial will tell us what the most effective treatment is for nerve damage causing pain in people with diabetes.

Project Status: Ongoing

URL for project: http://www.nets.nihr.ac.uk/projects/hta/153503

Anticipated Publish Date: 2021

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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