Clinical trial NCT01510457: Milnacipran for Chronic Pain in Knee Osteoarthritis
Official title: Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Knee Osteoarthritis
Degenerative Joint Disease
Chronic Pain
Keywords: Knee Osteoarthritis
Degenerative Joint Disease
Chronic Pain
Knee Pain
Lead sponsor: Shirley Ryan AbilityLab
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2012-01-16
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: McGill Pain Questionnaire - Short Form
timeFrame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
measure: PamSys Actigraph Data
timeFrame: 48 hours after visit 3
measure: Pain Anxiety Symptoms Scale (PASS)
timeFrame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
measure: Pain Disability Index (PDI)
timeFrame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
measure: Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
timeFrame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
measure: Pain Visual Analogue Scale
timeFrame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Secondary outcomes:
measure: Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
timeFrame: electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11
Other outcomes:
Locations:
Study officials:
affiliation: Center for Pain Studies, Rehabilitation Institute of Chicago
name: Norman Harden, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.