Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis
The present study will aim to evaluate the efficacy of milnacipran in the treatment of pain due to osteoarthritis (OA), that is, to determine whether milnacipran provides superior efficacy to placebo in patients with OA. Milnacipran is a serotonin-norepinephrine reuptake inhibitor (SNRI) that is currently approved in the United States in the treatment of major depressive disorder and fibromyalgia. There is increased evidence to suggest that SNRIs may be effective in the treatment of chronic pain conditions, such as OA.
The hypothesis in this study is that the survival time (time from randomization to loss of efficacy) of milnacipran group is superior to that of placebo group.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis|
- Time to loss of efficacy in the Double-Blind Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]The time to pain worsening by 30% compared to the value at baseline and a pain score of at least 4 on the 0-10 numerical rating scale on weekly pain assessment. Subjects who drop out due to "lack of efficacy" will be counted as efficacy failures regardless of their pain scores.
- Mean change in pain intensity [ Time Frame: 28 days ] [ Designated as safety issue: No ]Mean change in pain intensity on the 0-10 numerical rating scale from baseline in the Double-Blind Period.
- Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores [ Time Frame: 28 days ] [ Designated as safety issue: No ]Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores from Baseline in the Open-Label Period and Double-Blind Period.
- The efficacy of milnacipran vs. placebo by time to dropout for all causes [ Time Frame: 70 days ] [ Designated as safety issue: No ]
- The efficacy of milnacipran in the Open-Label Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]The efficacy of milnacipran in the Open-Label Period defined by the change in pain intensity from Baseline to the end of the period and responder proportion.
- The difference between milnacipran and placebo in responder proportion in the Double-Blind Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]
- The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo [ Time Frame: 70 days ] [ Designated as safety issue: No ]
- Safety and tolerability by monitoring adverse events [ Time Frame: 70 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||September 2012|
|Estimated Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
If subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The milnacipran arm will take milnacipran at 200mg/day (100mg twice daily).
1 tablet (100mg) by mouth twice daily for 28 days
Placebo Comparator: Placebo
If subjects meet the criteria to enter the Double-Blind Period, they will be randomized at a 1:1 ratio to take either milnacipran or placebo for 4 weeks. The placebo group will take 1 tablet twice daily.
1 tablet by mouth twice daily for 28 days
The study design is a Double-Blind, Placebo-Controlled, Enriched Enrollment Randomized Withdrawal Study. This means that, upon entry into the study, all subjects will enter an open-label period during which they will take milnacipran for 4 weeks. Subjects will taper their dose up to one 100mg tablet twice daily for a total of 200mg per day. After 4 weeks, the subject will return to the clinic and be re-evaluated.
Only subjects who meet certain criteria are then randomized to continue in the double-blind period of the study. Once a subject is randomized, he or she will take either milnacipran or placebo for another 4 weeks. Following the double-blind period, subjects will be tapered off the study medication and will receive a phone call once each week for 2 weeks for follow-up assessments.
Throughout the study, subjects will complete various questionnaires and other test procedures aimed at sub-typing subjects based on pain mechanisms.
|United States, Massachusetts|
|Natick, Massachusetts, United States, 01760|
|Contact: Karen Cowles, RN, MPH 781-444-9605 ext 121 email@example.com|
|Contact: Courtney Lincoln 781-444-9605 ext 119 firstname.lastname@example.org|
|Principal Investigator: Stephen L. Wright, M.D.|
|Sub-Investigator: Nathaniel P. Katz, M.D., M.S.|
|Sub-Investigator: Eric Osgood, M.D.|
|Principal Investigator:||Stephen L. Wright, M.D.||Analgesic Solutions|