Clinical trial NCT01329406: Study to Evaluate the Efficacy of Milnacipran in the Treatment of Pain Due to Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Osteoarthritis
Keywords: Osteoarthritis (OA)
Milnacipran
Serotonin-norepinephrine reuptake inhibitor (SNRI)
Knee pain
Lead sponsor: Analgesic Solutions
Sponsor class: INDUSTRY
Collaborators: name: Forest Laboratories
First posted: 2011-04-05
Enrollment: 50
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Be 21-75 years of age and in good general medical and psychological health
* Be able to speak, read, write, and understand English, understand the consent form, complete study related procedures, and communicate with the study staff
* Have a negative urine pregnancy test at screening, and use appropriate birth control
* Have documented painful Osteoarthritis (OA) of at least one knee for at least 6 months; OA should be of Class I-III and meet the American College of Rheumatology (ACR) clinical classification criteria, defined as:

  1. Knee pain and at least 3 of the following 6:

     * Age \> 50
     * Morning stiffness \< 30 minutes
     * Crepitus on active motion
     * Bony tenderness
     * Bony enlargement
     * No palpable warmth of synovium
  2. The target joint must not contain any type of orthopedic and/or prosthetic device
* Have a target joint pain average of 5 days per week and have an average pain intensity of at least 4/10 on the 0-10 NRS over the last 24 hours prior to screening
* Have stable treatment modalities, e.g. acupuncture, physical therapy
* Be willing to stop taking Non-steroidal Anti-inflammatory drugs (NSAIDs) and opioids for the duration of the study

Exclusion Criteria:

* Are allergic or intolerant to SNRI; have a previous poor response to a SNRI for OA pain; are currently taking an SNRI or tricyclic antidepressant
* Have a body mass index (BMI) \>40 kg/m2
* Have an Hospital Anxiety and Depression Scale (HADS) score \>12 on either subscale or has an established history of major depressive disorder not controlled with medication
* Have significant pain outside the target knee, including significant hip or back pain. (Bilateral knee OA allowed.)
* Have pain affecting the target knee that is due to any other etiology than OA
* Have documented history of inflammatory arthritis including rheumatoid arthritis
* Have had local injections in target joint within the past 3 months prior to screening
* Have had oral or intramuscular corticosteroids within the past 30 days
* Have had worker's compensation claim, disability, or litigation
* Have a known history of uncontrolled narrow-angle glaucoma
* Have a known history of suicidal ideation
* Use monoamine oxidase inhibitors (MAOI) concomitantly
* Are allergic or intolerant to acetaminophen
* Using opioids 4 or more days per week during the month preceding the screening visit
* Have significant history or renal impairment/failure.

Primary outcomes:
measure: Time to loss of efficacy in the Double-Blind Period
timeFrame: 28 days
Secondary outcomes:
measure: Mean change in pain intensity
timeFrame: 28 days
measure: Mean change in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores
timeFrame: 28 days
measure: The efficacy of milnacipran vs. placebo by time to dropout for all causes
timeFrame: 70 days
measure: The efficacy of milnacipran in the Open-Label Period
timeFrame: 28 days
measure: The difference between milnacipran and placebo in responder proportion in the Double-Blind Period
timeFrame: 28 days
measure: The predictive value of "OA sensory sub-type" for predicting the response to milnacipran vs. placebo
timeFrame: 70 days
measure: Safety and tolerability by monitoring adverse events
timeFrame: 70 days
Other outcomes:
Locations:
city: Natick
country: United States
facility: Analgesic Solutions
state: Massachusetts
Study officials:
affiliation: Analgesic Solutions
name: Stephen L. Wright, M.D.
role: PRINCIPAL_INVESTIGATOR
References: