Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Milnacipran
Intervention description: All subjects will be free of antidepressant medications or opiates, or any other medications used to treat pain for at least 2 weeks prior to initiation of dose titration. Patients will be allowed to escalate up to 100 mg a day: Day 1: 12.5 mg once a day; Days 2-3: 25 mg/day (12.5 mg twice daily); Days 4-7: 50 mg/day (25 mg twice daily); After Day 7: 100 mg/day (50 mg twice daily). The stable-dose phase will be a 10-week period during which patients will take medications at the final dose achieved (either 100 mg per day in divided doses, or the maximum tolerated dose of less than 100 mg per day).
Intervention MeSH terms: Milnacipran; Levomilnacipran
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Pain, Fatigue, Geriatric, Rheumatoid Arthritis, Milnacipran

Summary:

      The purpose of this study is to examine the effects of milnacipran for the treatment of pain
      in rheumatoid arthritis in older adults.
    

Eligibility criteria:

        Inclusion Criteria: Diagnosis. RA subjects will be evaluated by a board certified
        rheumatologist using revised criteria established by the American College of Rheumatology
        (ACR). This requires at least four of the following seven criteria: 1) morning joint
        stiffness; 2) arthritis in 3 or more joint areas; 3) arthritis of hand joints; 4) symmetric
        arthritis; 5) rheumatoid nodules; 6) presence of serum rheumatoid factor and 7) changes on
        posteroanterior hand and wrist radiographs. In addition, criteria 1-4 must be present for
        at least four weeks. Individuals diagnosed with juvenile RA will be excluded.

        Inclusion Criteria: Medication Use for RA patients. RA subjects taking disease modifying
        anti-rheumatic drugs (DMARDs) must be on a stable regime for one month before study and
        stable throughout study. RA subjects using DMARDs will be categorized as follows: 1) no
        DMARDs; 2) DMARD monotherapy with sulfasalazine, hydroxychloroquine, minocycline, or
        azothioprine, 3) DMARD monotherapy with methotrexate or leflunomide, 4) biologic therapy
        with or without concomitant DMARDs.

        Exclusion Criteria: Medical conditions. Subjects will not be eligible for the study based
        on the following criteria: (1) presence of acute or uncontrolled co-morbid medical
        conditions not limited to but including cardiovascular (e.g., history of acute coronary
        event, stroke, uncontrolled HTN) and neurological diseases (e.g., Parkinson's disease), as
        well as pain disorders; (2) presence of co-morbid inflammatory disorders such as Crohn's
        disease and ulcerative colitis and other autoimmune disorders; (3) presence of an
        uncontrolled medical condition that is deemed by the investigators to interfere with the
        proposed study procedures, or put the study participant at undue risk; (4) presence of
        chronic infections (e.g. positive purified protein derivative (PPD) test)) due to
        contraindication of tumor necrosis factor (TNF) antagonist use in these individuals and
        also because chronic infection can produce elevations in proinflammatory cytokines; (5)
        presence of an acute infectious illness in the two weeks prior to an experimental session;
        (6) pregnancy or breast-feeding because of the effects on neuroendocrine systems and sleep;
        (7) in women, the presence of vasomotor symptoms due to the effects of such symptoms on
        measures of sleep; (8) use of hormone containing medications including steroids; (9)
        current and/or regular use of nonsteroidal anti-inflammatory drug (NSAID) medications.

        Exclusion Criteria: Psychiatric Disorders. RA subjects with a current or lifetime history
        of a major Depressive Disorder or other Diagnostic and Statistical Manual of Mental
        Disorders IV (DSM-IV) psychiatric disorder (e.g. substance dependence) will be excluded due
        to the known effects of major depression on pain. Although depressive symptoms can occur in
        as many as 40% of RA patients, the prevalence of syndromal major depressive disorder is
        considerably less, and we do not anticipate that exclusion of current or lifetime history
        of major depressive disorder will substantially alter subject flow. More than 75% of a
        selected sample of RA subjects at University of California, Los Angeles (UCLA) affiliated
        clinics does not have a history of co-morbid psychiatric disorder.

        Exclusion Criteria: Medication use. Subjects who have used the following medications in the
        past two months will be excluded from the study: (1) previous use of Nitrogen Mustard,
        Cyclosporin, Cytotoxin, or Cyclophosphamide; (2) regular use of analgesics such as opioids,
        (3) regular use of prednisone >10mg of prednisone, (4) psychotropic medications, including
        selective serotonergic reuptake inhibitors, antidepressants, anxiolytics, hypnotics,
        sedatives and barbiturates. We will also exclude current smokers because of the known
        effects of tobacco use on proinflammatory cytokine levels. (Helen, I would suggest to
        remove this sentence. It is clear from studies that patients are higher risk for
        susceptibility and increased disease activity with smoking. It may decrease our
        enrollment.)