Pain Management in Osteoarthritis Using the Centrally Acting Analgesics Duloxetine and Pregabalin

Study Overview
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Brief Summary
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Osteoarthritis is the most common form of arthritis worldwide. Specifically, osteoarthritis of the hands affects millions of people and is a major cause of hand disability and pain. Despite this, there are currently no treatments that delay or halt the development of osteoarthritis. Pain is one of the major symptoms of osteoarthritis and pain management is an important factor to consider in the treatment of this condition. Treatments for pain in osteoarthritis consists of local injections, anti-inflammatory gels or painkillers such as paracetamol. However, most people with osteoarthritis still have pain despite these treatments.

Detailed Description
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Recent scientific studies have suggested that people with hand osteoarthritis not only feel pain in their hand joints, they also appear to have increased signals in their brain pain processing pathways. At St George's, University of London, the investigators have been conducting studies to find out which brain regions are activated in subjects with hand osteoarthritis. The investigators have found that certain brain regions (thalamus, insula, cingulate and somatosensory cortex) are activated during painful tasks in patients with hand osteoarthritis but not in healthy people. In this study the investigators will establish whether drugs that inhibit pain processing pathways in the brain can help. Patients who are still having pain despite their usual painkillers will be randomly divided into 3 groups: one group will receive a placebo, the other 2 groups will receive one of two different drugs, duloxetine or pregabalin. Participants will be assessed using questionnaires and a brain scan (functional MRI) before and after 13 weeks of taking the tablets. This study will help us to understand the ways in which people feel pain in osteoarthritis. If our trial proves successful,drugs that dampen central pain pathways could be used in combination with local pain-relieving drugs to improve treatment and reduce disability in patients with hand osteoarthritis.

Official Title
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Pain Management in Osteoarthritis Using the Centrally Acting Analgesics Duloxetine and Pregabalin

Conditions
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Hand Osteoarthritis

Intervention / Treatment
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* Drug: Pregabalin or Duloxetine or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants fulfilling the American College of Rheumatology (ACR) criteria for the diagnosis of hand osteoarthritis Participants with hand osteoarthritis presenting to rheumatology outpatient clinics and primary care. Participants will be right or left handed Male or female Age between 40 and 75 Participants will be on usual care for hand osteoarthritis including paracetamol and/or non-steroidal anti-inflammatory drugs Exclusion Criteria: Participants with other rheumatological diagnoses e.g. rheumatoid arthritis Current or planned pregnancy Contraindications to duloxetine or pregabalin History of depression Recent surgery Previous use of duloxetine and/or pregabalin

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pregabalin<br>Pregabalin 150mg ON week 1 increased to Pregabalin 300mg ON weeks 2-11 then decrease to Pregabalin 150mg ON week 12 then STOP | Drug: Pregabalin or Duloxetine or Placebo<br>* This is a randomized, double blind placebo controlled trial with a head-to-head comparison of duloxetine vs pregabalin vs placebo over-encapsulated to prevent unblinding of treatment arm<br>* Other names: DUPRO Capsules;|
| Active Comparator: Duloxetine<br>Duloxetine 30mg ON week 1 increase to Duloxetine 60mg weeks 2-11 then decrease to Duloxetine 30mg ON week 12 then STOP | Drug: Pregabalin or Duloxetine or Placebo<br>* This is a randomized, double blind placebo controlled trial with a head-to-head comparison of duloxetine vs pregabalin vs placebo over-encapsulated to prevent unblinding of treatment arm<br>* Other names: DUPRO Capsules;|
| Placebo Comparator: Placebo<br>1 capsule ON week 1- increase to 2 capsules ON week 2-11 then decrease to 1 capsule ON week 12 then STOP. | Drug: Pregabalin or Duloxetine or Placebo<br>* This is a randomized, double blind placebo controlled trial with a head-to-head comparison of duloxetine vs pregabalin vs placebo over-encapsulated to prevent unblinding of treatment arm<br>* Other names: DUPRO Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Australian/Canadian Hand Osteoarthritis Index score (AUSCAN) | The AUSCAN measures pain and hand function. Differences between baseline AUSCAN and after treatment will be recorded for each participant to assess for improvement in AUSCAN pain and function score after the trial intervention. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain magnetic resonance imaging (MRI) | Changes between baseline MRI and post-treatment after 12 weeks of intervention will be measured using functional neuroimaging to assess pain center activation before and after intervention. | Baseline and 12 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain