Milnacipran for Chronic Pain in Knee Osteoarthritis

NCT ID: NCT01510457

Last Updated: 2015-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-10-31

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.

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.

Conditions

Knee Osteoarthritis; Degenerative Joint Disease; Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sugar Pill

BID placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Milnacipran

Uptitration from 10mg to 50mg BID Milnacipran

Group Type: EXPERIMENTAL

Milnacipran

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Savella (milnacipran HCL) Tablets; "Sugar Pill"

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Dr. Norman Harden

OTHER

Sponsor Role: lead

Responsible Party

Dr. Norman Harden

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Norman Harden, MD

Role: PRINCIPAL_INVESTIGATOR

Center for Pain Studies, Rehabilitation Institute of Chicago

References

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.

Reference Type: DERIVED

PMID: 36269595 (View on PubMed)

Other Identifiers

SAV-MD-23

Identifier Type: -

Identifier Source: org_study_id