Milnacipran for Chronic Pain in Knee Osteoarthritis
Condition: Knee Osteoarthritis; Degenerative Joint Disease; Chronic Pain
MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Joint Diseases; Chronic Pain
Intervention: Milnacipran; Placebo
Intervention description: Total target dose of 200 mg/day. Subjects will titrate-up according to the following schedule: 25 mg/d (2 pills, 2 days), 50mg mg/d (4 pills, 2 days), 100mg/d (2 pills, 3 days), 150 mg/d (3 pills, 4 days), and steady state is reached once the study participant ingests 200 mg/d(4 pills). The steady state is maintained for 44 days (approx. 6 weeks). If intolerable side effects occur, the dose may be reduced to last tolerable does, a minimum of 100 mg/day at the discretion of the PI. Subjects unable to tolerate 100 mg/day will be discontinued from the study. A 2-week down-titration will be used.; Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
Intervention MeSH terms: Milnacipran; Levomilnacipran
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Knee Osteoarthritis; Degenerative Joint Disease; Chronic Pain; Knee Pain

Summary:

      The patients are asked to take part in this study because you have chronic pain as a result
      of knee osteoarthritis. This study is done to investigate the pain relieving effects of the
      study drug Savella (milnacipran HCl) for people who experience chronic osteoarthritis pain.
      The purpose of this research is to look at how the study drug can be used to benefit people
      who experience osteoarthritis knee pain. This is a phase IV study done to study the safety
      and effectiveness of the drug. At this point the drug is already approved by the Food and
      Drug Administration for people with fibromyalgia but it has not yet been approved for people
      with knee osteoarthritis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Knee pain and osteophytes on radiographs OR

          -  Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes
             or less, and crepitus (cracking sound) during motion

          -  Experiences chronic pain for 6 months or longer

          -  Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale

          -  If female, is not pregnant or breast feeding, and not currently attempting to
             conceive; if of childbearing potential, use of a highly effective method of birth
             control (as determined by Pl)

          -  Able to walk at least ½ a city block a day, and agrees to try and slowly increase that
             over the course of study

          -  Able to read and speak English and provide informed consent

          -  Able to understand and comply with all data collection methodology including
             electronic diary

          -  Subject agrees to 1) continue their stable drug regimen with no changes during the
             course of study, 2) only use Tylenol 325 mg of tablets (a maximum of 8 tablets a day)
             for breakthrough pain, and 3) not use Tylenol or any other pain medicines 12 hours
             before testing.

        Exclusion Criteria:

          -  Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake
             blockers for mood disorders

          -  Subject is allergic to SSRIs, SNRIs, or milnacipran

          -  Subject has severe or untreated psychiatric disturbance (e.g. mania, depression,
             anxiety, substance dependence)

          -  Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or
             heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or
             digoxin during the trial

          -  Subject has a clinical diagnosis of fibromyalgia

          -  Subject has severe ongoing or unaddressed medical conditions (e.g. Renal or Hepatic
             disease [creatinine>1.5 ml/dl; AST or ALT> 3x normal limit], uncontrolled
             hypertension, severe cardiac rate or rhythm disorders, rheumatologic disease (e.g.
             polymyalgia rheumatica), narrow angle glaucoma, hyponatremia, clotting disorders,
             uncontrolled seizure disorder or urinary retention)

          -  Subject has cardiac implants

          -  Subject has a knee replacement

          -  Subject plans to start new pain treatments or therapies during the study (e.g. new
             pain medication, injections, PT, surgery)