Milnacipran in the Treatment of Widespread, Non-Joint Pain in Rheumatoid Arthritis

• Status: Completed
• Trial end date: 2013-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether milnacipran reduces widespread, non-joint pain in patients with rheumatoid arthritis (RA). The investigators will conduct a double-blind randomized crossover trial in subjects with RA to test the hypothesis that milnacipran improves widespread, non-joint pain. The investigators will also use data from the trial to determine whether response to milnacipran is associated with pain-modulating mechanisms from the central nervous system. The investigators hypothesize that response to milnacipran will be greater among patients with impaired central pain mechanisms than among patients with intact central pain modulating mechanisms.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborators: Forest Laboratories; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Treatments: Levomilnacipran; Milnacipran

Criteria

Inclusion Criteria:

• Age 24 years or older

• Primary diagnosis of rheumatoid arthritis from a board-certified rheumatologist

• Willing to maintain stable doses of concurrent non-steroidal anti-inflammatory drugs or other acceptable medications or therapies for the duration of the study

• Brief Pain Inventory Average Pain >= 4 at the screening visit

• Widespread Pain Index >= 5 at the screening visit

• Able to give informed consent

Exclusion Criteria:

• Diagnosis of primary fibromyalgia

• Diagnosis of cold sensitive conditions such as Raynaud's syndrome, cryoglobulinemia and paroxysmal cold hemoglobinuria

• Diagnosis of psychotic disorders, such as schizophrenia, schizoaffective disorder, delusional disorder and shared psychotic disorder

• Patients being treated with SSRIs, MAO inhibitors or tricyclic, tetracyclic or atypical antidepressants for pain may participate in this study if they are washed off these medications before study entry. Patients currently receiving therapy with SSRIs or tricyclic, tetracyclic or atypical antidepressants for depression may be washed off these medications before study entry pending permission of the prescribing physician and if they have never received a diagnosis of major depressive disorder or had a history of suicidal ideation.

• Patients on thioridazine or MAO inhibitors

• Patients taking codeine or other opioids/opiates. Patients who are taking medications such as pregabalin (Lyrica) and gabapentin (Neurontin) for pain may be enrolled in this study.

• Known hypersensitivity to milnacipran

• Patients with a significant risk of suicide as assessed by the Beck depression inventory form

• Patients with a history of suicide

• Pregnant or breast-feeding women

• Patients with an actively pending worker's compensation claim or auto no-fault claim; patients with current worker's compensation, auto no-fault compensation, or litigation; or any patient with significant secondary gain issues per discretion of the researchers.

• Patients with myocardial infarction within the past 12 months, active cardiac disease (chest pain or evidence of ischemia on stress test), acute congestive heart failure requiring hospitalization in the past 12 months, clinically significant cardiac rhythm or conduction abnormalities requiring hospitalization in the past 12 months

• Patients with severe liver impairment (AST or ALT > 3 times the upper limit of normal)

• For patients 2-3 times the upper limit of normal, we will obtain enrollment permission from the patient's hepatologist and monitor values at each study visit. If values increase above 3 times the upper limit of normal, the patient will be discontinued from the study.

• For patients 1-2 times the upper limit of normal, we will obtain enrollment permission from the patient's physician and monitor per request of the physician.

• Patients with severe or end stage renal disease, defined as a GFR < 15 ml/min or on dialysis

• Patients with a recent (≤ 12 months) history of seizures.

• Patients with uncontrolled narrow-angle glaucoma.

• Patients who have been treated with an experimental agent within the last three months.