Milnacipran in the Treatment of Widespread, Non-Joint Pain in Rheumatoid Arthritis
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Milnacipran; Placebo
Intervention description: Milnacipran comes in 50 mg tablets and is taken orally. Participants will gradually be increased to a target dose of 50 mg twice daily.
Intervention MeSH terms: Milnacipran; Levomilnacipran
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 49.0
Sex: All
Minimum age: 24 Years
Healthy volunteers: No
Keywords: Arthritis, Rheumatoid; Milnacipran; Pain

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.
    

Eligibility 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.