Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Milnacipran for Chronic Pain in Knee Osteoarthritis (KOA)

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Dr. Norman Harden, Rehabilitation Institute of Chicago
ClinicalTrials.gov Identifier:
NCT01510457
First received: November 29, 2011
Last updated: October 29, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Knee Osteoarthritis
Degenerative Joint Disease
Chronic Pain
Drug: Milnacipran
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis

Resource links provided by NLM:


Further study details as provided by Rehabilitation Institute of Chicago:

Primary Outcome Measures:
  • The efficacy of Milnacipran (Savella), measured by the change of knee pain, in treating chronic knee osteoarthritis pain. [ Time Frame: 3 visits over 11 weeks: Visit 1 (week 1), Visit 2 (week 2) and Visit 3 (Week 9). In addition, we will have electronic diary entries with pain, fatigue and functioning scores three times a day for 79 days. ] [ Designated as safety issue: No ]
    Intent to treat analyses will compare data from the groups for all participants with at least two data points. A series of mixed design ANOVAs will be completed with data from objective functional testing, quasi-objective functional and psychophysical testing, subject pain questionnaires and subjective perceived function and quality of life.


Secondary Outcome Measures:
  • Change of physical functional ability due to change in knee pain [ Time Frame: 3 visits over 11 weeks: Visit 1 (week 1), Visit 2 (week 2) and Visit 3 (Week 9). In addition, we will have electronic diary entries with pain, fatigue and functioning scores three times a day for 79 days. ] [ Designated as safety issue: No ]
    A second set of follow-up analyses will test for nonlinear patterns of change over time. It is expected that some outcome factors will show quadratic trends such that, for instance, activity level will change depending on pain ratings.


Enrollment: 36
Study Start Date: November 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill Drug: Placebo
Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
Experimental: Milnacipran Drug: Milnacipran
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.
Other Name: Savella (milnacipran HCL) Tablets

Detailed Description:

If you are in this study, you will be placed in one of two study groups: one group will receive the study drug and one will receive a placebo. You will be assigned a study group by chance using a process similar to the flip of a coin.

At the first visit (week one) we will review and sign the informed consent, obtain your medical health history, and conduct a brief physical exam. You will also complete several questionnaires about your pain. You will be assessed for your eligibility to participate in this study. If you are eligible, we will conduct some physical and sensory tests and collect a blood sample. The physical tests include a stair climb, 6-minute treadmill test and a 1-minute sit to stand test. The sensory tests allow us to understand your perception of various stimuli such as vibration, light touch, pinprick, heat, cold, hot pain, and cold pain. At the end of the first visit you will be given an electronic diary to record your pain throughout the study. We will also ask you to wear a device in a T-shirt, similar to an accelerometer, that will be used to record your sleep quality and physical activity for 2 days.

At the second (week two) and third visits (week nine) you will be asked to complete the same questionnaires, physical and sensory tests as during the first visit. You will also have to wear the t-shirt with the device for 2 days after each visit.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  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: NCT01510457

Locations
United States, Illinois
Rehabilitation Institute of Chicago, Center for Pain Studies
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Dr. Norman Harden
Forest Laboratories
Investigators
Principal Investigator: Norman Harden, MD Center for Pain Studies, Rehabilitation Institute of Chicago
  More Information

No publications provided

Responsible Party: Dr. Norman Harden, Principal Investigator, Rehabilitation Institute of Chicago
ClinicalTrials.gov Identifier: NCT01510457     History of Changes
Other Study ID Numbers: SAV-MD-23
Study First Received: November 29, 2011
Last Updated: October 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Rehabilitation Institute of Chicago:
Knee Osteoarthritis
Degenerative Joint Disease
Chronic Pain
Knee Pain

Additional relevant MeSH terms:
Chronic Pain
Joint Diseases
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Pain
Rheumatic Diseases
Signs and Symptoms
Milnacipran
Adrenergic Agents
Adrenergic Uptake Inhibitors
Antidepressive Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014