Milnacipran for Chronic Pain in Knee Osteoarthritis

NCT01510457 | Completed Phase 4 Results

• 1 other identifier: SAV-MD-23
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Knee Osteoarthritis; Degenerative Joint Disease; Chronic Pain

Keywords

Knee Osteoarthritis; Degenerative Joint Disease; Chronic Pain; Knee Pain

Outcome Measures

Primary Outcomes (6)

• McGill Pain Questionnaire - Short Form

  The MPQ-SF is a well-validated pain measure that permits separation of the sensory and affective components of pain, which are added together to compute a total score. The scale ranges from 0-45 (0=no pain, 45=the most pain).

  Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.

• PamSys Actigraph Data

  We used a body worn sensor (PAMSys™, Biosensics, LLC, MA)(25-27) embedded in a comfortable t-shirt at the sternal level. Participants wore the PAMSys after the visit for 48 hours. The device provides values related to subjects spontaneous physical activity including percentage of time standing and walking. These variables provide different indexes of participants' level of activity and activity organization, and were reported by subjects with KOA pain as relevant.

  48 hours after visit 3

• Pain Anxiety Symptoms Scale (PASS)

  Anxiety scores were collected at least two data points. The Pain Anxiety Symptoms Scale (PASS) is a scale from 0 - 100, where 0 = no anxiety and 100 = the most anxiety.

  Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.

• Pain Disability Index (PDI)

  The PDI is a seven-item, validated instrument that assesses perceived disability in seven key life areas. It provides a total disability score, and is an indirect measure of self efficacy. The Pain Disability Scale is a scale from 0 - 70, where 0 = no Disability and 70 = the most Disability.

  Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.

• Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)

  The CES-D 10 is a 10-item questionnaire that has been validated for the assessment of depressive symptomatology. The Depression Scale is a scale with a sum score from 0 - 30, where 0 = no Depression and 30 = the most Depression.

  Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.

• Pain Visual Analogue Scale

  Pain Visual Analogue Scale from 0-100 (0= no pain, and 100= most pain).

  Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.

Secondary Outcomes (1)

• Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day

  electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11

Study Arms (2)

Sugar Pill

PLACEBO COMPARATOR

BID placebo

Drug: Placebo

Milnacipran

EXPERIMENTAL

Uptitration from 10mg to 50mg BID Milnacipran

Drug: Milnacipran

Interventions

Milnacipran DRUG

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.

Also known as: Savella (milnacipran HCL) Tablets

Milnacipran

Placebo DRUG

Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.

Also known as: "Sugar Pill"

Sugar Pill

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Dr. Norman Harden: lead
• Forest Laboratories: collaborator

Related Publications (1)

• Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD012157. doi: 10.1002/14651858.CD012157.pub2.

  PMID: 36269595 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Joint Diseases; Chronic Pain

Interventions

Milnacipran; Tablets; Sugars

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Musculoskeletal Diseases; Rheumatic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclopropanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Carbohydrates

Results Point of Contact

• Title: Dr. R. Norman Harden
• Organization: Rehabilitation Institute of Chicago Center for Pain Studies

centerforpainstudies@ric.org

312.238.5654

Study Officials

• Norman Harden, MD

  Center for Pain Studies, Rehabilitation Institute of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: January 16, 2012
• Study Start: November 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 22, 2015
• Results First Posted: January 22, 2015

Record last verified: 2015-05