Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis

NCT ID: NCT01225991

Last Updated: 2018-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-06-30

Brief Summary

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

Detailed Description

This is a 12-week open-label trial of milnacipran for the treatment of pain in rheumatoid arthritis in older adults. The investigators are interested in the relationship of chronic pain to inflammation, resilience, fatigue, and physical and mental functioning. The investigators anticipate that effective pain reduction will result in improved fatigue, resilience, physical and mental functioning and reduced levels of inflammation. The investigators are seeking to examine this directly in 30 older adults (55 years of age or older) with rheumatoid arthritis who will be using milnacipran for treatment of pain in the absence of clinical major depression. This proposed trial will serve as a pilot study to estimate the effect of the drug on pain and functional outcomes, as well as aid in dose-finding in this population.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Milnacipran, active drug, open-label

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, or to their maximum tolerated dose in the course of the first week. 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). Final efficacy assessments will be made at the termination visit, and the study medication will be tapered down following 12 weeks of drug treatment.

Group Type: EXPERIMENTAL

Milnacipran

Intervention Type: DRUG

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).

Interventions

Milnacipran

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 Type: DRUG

Other Intervention Names

Savella

Eligibility Criteria

Inclusion 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.)

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Helen Lavretsky, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Helen Lavretsky, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA Semel Institute

Los Angeles, California, United States

Countries

United States

Related Links

http://www.semel.ucla.edu/latelife

Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis

Other Identifiers

SAV-MD-10

Identifier Type: -

Identifier Source: org_study_id