Milnacipran for Chronic Pain in Knee Osteoarthritis

Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01510457

Acronym

KOA

Enrollment

Registered

2012-01-16

Start date

2010-11-30

Completion date

2013-10-31

Last updated

2015-06-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Pain, Degenerative Joint Disease, Knee Osteoarthritis

Keywords

Knee Osteoarthritis, Degenerative Joint Disease, Chronic Pain, Knee Pain

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.

Interventions

DRUGMilnacipran

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.

DRUGPlacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 90 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Pain Anxiety Symptoms Scale (PASS)	Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.	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.
McGill Pain Questionnaire - Short Form	Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.	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).
PamSys Actigraph Data	48 hours after visit 3	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.
Pain Visual Analogue Scale	Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.	Pain Visual Analogue Scale from 0-100 (0= no pain, and 100= most pain).
Pain Disability Index (PDI)	Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.	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.
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)	Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.	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.

Secondary

Measure	Time frame	Description
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	Averages of daily diary outcomes were taken over the first and last week of the trial (week 1 and week 11) to compare pre and post treatment. diary was filled out 3 times a day and asked subjects to rate pain at rest, pain when walking, and fatigue on a scale 0-10 (0=none, and 10=the worst)

Participant flow

Participants by arm

Arm	Count
Sugar Pill Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.	12
Milnacipran 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.	26
Total	38

Baseline characteristics

Characteristic	Sugar Pill	Milnacipran	Total
Age, Continuous	53 years STANDARD_DEVIATION 7	57 years STANDARD_DEVIATION 9	56 years STANDARD_DEVIATION 8
Region of Enrollment United States	12 participants	26 participants	38 participants
Sex: Female, Male Female	6 Participants	17 Participants	23 Participants
Sex: Female, Male Male	6 Participants	9 Participants	15 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	9 / 26	0 / 12
serious Total, serious adverse events	0 / 26	0 / 12

Outcome results

Primary

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.