Trial Outcomes & Findings for Milnacipran for Chronic Pain in Knee Osteoarthritis (NCT NCT01510457)
NCT ID: NCT01510457
Last Updated: 2015-06-22
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
46 participants
Primary outcome timeframe
Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Results posted on
2015-06-22
Participant Flow
Participant milestones
| Measure |
Sugar Pill
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
29
|
|
Overall Study
COMPLETED
|
12
|
26
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Milnacipran for Chronic Pain in Knee Osteoarthritis
Baseline characteristics by cohort
| Measure |
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
Milnacipran
n=26 Participants
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.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53 years
STANDARD_DEVIATION 7 • n=5 Participants
|
57 years
STANDARD_DEVIATION 9 • n=7 Participants
|
56 years
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
12 participants
n=5 Participants
|
26 participants
n=7 Participants
|
38 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
McGill Pain Questionnaire - Short Form
MPQ-SF (total) Visit 1
|
10.5 units on a pain scale
Standard Deviation 7.3
|
15.7 units on a pain scale
Standard Deviation 12.2
|
|
McGill Pain Questionnaire - Short Form
MPQ-SF (total) Visit 3
|
6.0 units on a pain scale
Standard Deviation 5.9
|
12.3 units on a pain scale
Standard Deviation 9.6
|
PRIMARY outcome
Timeframe: 48 hours after visit 3We 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.
Outcome measures
| Measure |
Milnacipran
n=12 Participants
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.
|
Sugar Pill
n=26 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
PamSys Actigraph Data
percentage of time standing
|
18.154 percentage of activity (over 48 hours)
Standard Error 1.816
|
17.675 percentage of activity (over 48 hours)
Standard Error 1.218
|
|
PamSys Actigraph Data
percentage of time walking
|
10.218 percentage of activity (over 48 hours)
Standard Error 1.440
|
11.198 percentage of activity (over 48 hours)
Standard Error .966
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
Pain Anxiety Symptoms Scale (PASS)
PASS-20 (total) Visit 1
|
34.5 units on an anxiety scale
Standard Deviation 18.6
|
39.1 units on an anxiety scale
Standard Deviation 23.8
|
|
Pain Anxiety Symptoms Scale (PASS)
PASS-20 (total) Visit 3
|
22.0 units on an anxiety scale
Standard Deviation 13.7
|
31.2 units on an anxiety scale
Standard Deviation 22.6
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
Pain Disability Index (PDI)
Pain Disability Index (total)_Visit 1
|
28 units on a disability scale
Standard Deviation 14
|
31 units on a disability scale
Standard Deviation 11
|
|
Pain Disability Index (PDI)
Pain Disability Index (total)_Visit 3
|
15 units on a disability scale
Standard Deviation 10
|
26 units on a disability scale
Standard Deviation 18
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
CES-D-10 (total) Visit 1
|
7 units on the depression scale
Standard Deviation 5
|
6 units on the depression scale
Standard Deviation 4
|
|
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
CES-D-10 (total) Visit 3
|
6 units on the depression scale
Standard Deviation 4
|
9 units on the depression scale
Standard Deviation 7
|
PRIMARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
Pain Visual Analogue Scale
VAS now Visit 1
|
44 units on a 100mm pain scale
Standard Deviation 24
|
55 units on a 100mm pain scale
Standard Deviation 28
|
|
Pain Visual Analogue Scale
VAS now Visit 3
|
20 units on a 100mm pain scale
Standard Deviation 22
|
51 units on a 100mm pain scale
Standard Deviation 24
|
SECONDARY outcome
Timeframe: electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11Averages 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)
Outcome measures
| Measure |
Milnacipran
n=26 Participants
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.
|
Sugar Pill
n=12 Participants
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Pain at rest reported on Diary over Week 1
|
4.1 units on a 0-10 NRS scale
Standard Deviation 2.1
|
5.6 units on a 0-10 NRS scale
Standard Deviation 2.1
|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Pain at rest reported on Diary over Week 11
|
2.0 units on a 0-10 NRS scale
Standard Deviation 1.5
|
3.7 units on a 0-10 NRS scale
Standard Deviation 1.9
|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Pain walking reported on Diary over Week 1
|
5.2 units on a 0-10 NRS scale
Standard Deviation 2.0
|
6.4 units on a 0-10 NRS scale
Standard Deviation 2.1
|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Pain walking reported on Diary over Week 11
|
3.1 units on a 0-10 NRS scale
Standard Deviation 1.7
|
4.6 units on a 0-10 NRS scale
Standard Deviation 2.0
|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Fatigue reported on Diary over Week 1
|
4.3 units on a 0-10 NRS scale
Standard Deviation 2.0
|
4.4 units on a 0-10 NRS scale
Standard Deviation 2.8
|
|
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Ave Fatigue reported on Diary over Week 11
|
3.4 units on a 0-10 NRS scale
Standard Deviation 2.4
|
2.8 units on a 0-10 NRS scale
Standard Deviation 1.5
|
Adverse Events
Milnacipran
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Sugar Pill
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Milnacipran
n=26 participants at risk
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.
|
Sugar Pill
n=12 participants at risk
Placebo: Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
|
|---|---|---|
|
General disorders
Nausea
|
11.5%
3/26
|
0.00%
0/12
|
|
General disorders
Fatigue
|
11.5%
3/26
|
0.00%
0/12
|
|
General disorders
Trouble Sleeping
|
7.7%
2/26
|
0.00%
0/12
|
|
General disorders
Constipation
|
7.7%
2/26
|
0.00%
0/12
|
|
General disorders
Headache
|
7.7%
2/26
|
0.00%
0/12
|
|
Cardiac disorders
Transient tachycardia
|
3.8%
1/26
|
0.00%
0/12
|
|
Renal and urinary disorders
Urinary Retention
|
3.8%
1/26
|
0.00%
0/12
|
Additional Information
Dr. R. Norman Harden
Rehabilitation Institute of Chicago Center for Pain Studies
Phone: 312.238.5654
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place