Milnacipran for Treatment of Pain in Older Adults With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Helen Lavretsky, MD, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT01225991
First received: October 20, 2010
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Milnacipran
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Trial of Milnacipran for the Treatment of Pain in Rheumatoid Arthritis (RA) in Older Adults

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Pain Rating Index [ Time Frame: Change score at baseline and 12 weeks ] [ Designated as safety issue: No ]
    Pain & Stiffness: Repeated assessments of pain and stiffness across the day will utilize the Pain Rating Index (PRI), consisting of the sum of the ranked values associated with adjectives depicting the severity of pain from the McGill Pain Questionnaire (MPQ). Sixty joints will be evaluated on a scale from 0 (none) to 3 (severe), to indicate the extent of pain/tenderness and swelling. The final score was summed for this measure with a range from 0 (no pain) to 45 (worst possible pain).


Secondary Outcome Measures:
  • Visual Analogue Scale to Evaluate Fatigue (VAS-F) [ Time Frame: Week 1 and 12 ] [ Designated as safety issue: No ]
    Fatigue: Repeated assessment of fatigue severity across the day will utilize the Visual Analogue Scale to Evaluate Fatigue (VAS-F).

  • (UKU) Side Effects Rating Scale Profile [ Time Frame: 12 weeks- each visit ] [ Designated as safety issue: Yes ]
    Will rate the frequency and intensity of emerging adverse events.

  • Profile of Mood States (POMS) [ Time Frame: Week 1 and 12 ] [ Designated as safety issue: No ]
    Depressive symptoms: Repeated assessment of depressive symptoms severity will be made using the Profile of Mood States (POMS).

  • Connor-Davidson Resilience Scale (CD-RISC) [ Time Frame: Week 1 and 12 ] [ Designated as safety issue: No ]
    Resilience: the Connor-Davidson Resilience scale (CD-RISC) quantifies stress coping ability.


Enrollment: 18
Study Start Date: November 2010
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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).
Other Name: Savella

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225991

Locations
United States, California
UCLA Semel Institute
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
Forest Laboratories
Investigators
Principal Investigator: Helen Lavretsky, M.D. University of California, Los Angeles
  More Information

Additional Information:
No publications provided

Responsible Party: Helen Lavretsky, MD, Professor, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01225991     History of Changes
Other Study ID Numbers: SAV-MD-10
Study First Received: October 20, 2010
Results First Received: August 12, 2014
Last Updated: September 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Pain, Fatigue, Geriatric, Rheumatoid Arthritis, Milnacipran

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Milnacipran
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Adrenergic Uptake Inhibitors
Adrenergic Agents

ClinicalTrials.gov processed this record on September 22, 2014