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

NCT01207453 | Completed Phase 4 Results DMC

• 2 other identifiers: SAV-MD-16K23AR057578
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Arthritis, Rheumatoid

Keywords

Arthritis, Rheumatoid; Milnacipran; Pain

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory (BPI) Change

  A measure of change in scores on the BPI short form, a "24-hr average pain" item, from baseline to 6 weeks, The BPI short form scores ranges from 0-10, with 10 being the worst pain.

  Baseline to 6 weeks

Secondary Outcomes (6)

• Change in Conditioned Pain Modulation (CPM)

  Baseline to 6 weeks

• Symptom Intensity Scale (SIS)

  Baseline to 6 weeks

• Thumbnail Pain Threshold

  Baseline to 6 weeks

• Trapezius Pain Threshold

  Baseline to 6 weeks

• Wrist Pain Threshold

  Baseline to 6 weeks

Study Arms (2)

Milnacipran then placebo

OTHER

This arm of the study will contain half the study population after randomization. The participants in this arm will receive milnacipran for 6 weeks. They will undergo a one-week taper and a two week washout period and then crossover to a placebo for 6 weeks.

Drug: Milnacipran; Drug: Placebo

Placebo then milnacipran

OTHER

This arm of the study will contain half the study population after randomization. The participants in this arm will receive placebo for 6 weeks. They will undergo a one-week "taper" and a two week "washout" period and then crossover to milnacipran for 6 weeks.

Drug: Milnacipran; Drug: Placebo

Interventions

Milnacipran DRUG

Milnacipran comes in 50 mg tablets and is taken orally. Participants will gradually be increased to a target dose of 50 mg twice daily.

Also known as: Savella

Milnacipran then placebo; Placebo then milnacipran

Placebo DRUG

Milnacipran then placebo; Placebo then milnacipran

Eligibility Criteria

• Age: 24 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Forest Laboratories: collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Lee YC, Chibnik LB, Lu B, Wasan AD, Edwards RR, Fossel AH, Helfgott SM, Solomon DH, Clauw DJ, Karlson EW. The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study. Arthritis Res Ther. 2009;11(5):R160. doi: 10.1186/ar2842. Epub 2009 Oct 29.

  PMID: 19874580 BACKGROUND

• Lee YC, Massarotti E, Edwards RR, Lu B, Liu C, Lo Y, Wohlfahrt A, Kim ND, Clauw DJ, Solomon DH. Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial. J Rheumatol. 2016 Jan;43(1):38-45. doi: 10.3899/jrheum.150550. Epub 2015 Dec 1.

  PMID: 26628607 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Pain

Interventions

Milnacipran

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Yvonne C Lee, MD, MMSc
• Organization: Brigham and Women's Hospital

ylee9@partners.org

617-732-8736

Study Officials

• Yvonne C Lee, MD, MMSc

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yvonne C. Lee, MD, MMSc

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 23, 2010
• Study Start: January 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 17, 2014
• Results First Posted: November 17, 2014

Record last verified: 2014-11

Locations

US (1)