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Trial record 25 of 88 for:    "Neuromuscular Disease" | "Norepinephrine"

A Study to Evaluate the Effects of Milnacipran on Pain Processing and Functional MRI in Patients With Fibromyalgia

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ClinicalTrials.gov Identifier: NCT01173055
Recruitment Status : Completed
First Posted : July 30, 2010
Results First Posted : February 20, 2015
Last Update Posted : November 8, 2017
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Daniel Clauw, MD, University of Michigan

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition Fibromyalgia
Interventions Drug: milnacipran
Drug: Placebo
Enrollment 22
Recruitment Details  
Pre-assignment Details Participants enrolled in the study received placebo for 1 week (Day -7 to 0) then began the double blinded treatment sequence.
Arm/Group Title Milnacipran First, Then Placebo Placebo First, Then Milnacipran
Hide Arm/Group Description

Milnacipran then placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran First, Then Placebo: Period 1 (Day 1-49); Milnacipran 12.5mg by mouth (PO) Day 1; 12.5mg twice daily (BID) Day 2 to 3; 25mg BID Day 4 to 7; 50mg BID Day 8-14; 100mg BID Day 15-42 followed by taper Day 43-49 and a 14 day washout period. Then, placebo matching study treatment in similar pattern to Period 1 was administered beginning Period 2 (Day 64-112).

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo First, Then Milnacipran: Period 1 (Day 1-49); Placebo matching study treatment was administered beginning Period 1 (Day 1-49) and a 14 day washout period. Then, Milnacipran Period 2 (Day 64-112); Milnacipran 12.5mg Day 62; 12.5mg twice daily (BID) Day 65 to 66; 25mg BID Day 67 to 70; 50mg BID Day 71-77; 100mg BID Day 78-105 followed by taper Day 106-112.

Period Title: Period 1 - Day 1 to 49
Started 10 12
Completed 8 10
Not Completed 2 2
Reason Not Completed
Withdrawal by Subject             2             2
Period Title: Placebo Washout Period - Day 50 to 63
Started 8 10
Completed 8 10
Not Completed 0 0
Period Title: Period 2 - Day 64 to 112
Started 8 10
Completed 8 9
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Arm/Group Title Milnacipran First, Then Placebo Placebo First, Then Milnacipran Total
Hide Arm/Group Description

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Total of all reporting groups
Overall Number of Baseline Participants 6 9 15
Hide Baseline Analysis Population Description
The milnacipran then placebo arm was reduced from eight to six participants for the analysis due to tolerating a dose of Milnacipran less than 200mg/day. This was done to be consistent with the dosing of all other participants.
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Fibromyalgia Number Analyzed 6 participants 9 participants 15 participants
46.83  (9.83) 36.67  (8.64) 40.73  (10.187)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Female Number Analyzed 6 participants 9 participants 15 participants
6 9 15
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 9 participants 15 participants
6 9 15
1.Primary Outcome
Title Pain Threshold at Baseline
Hide Description The primary outcome parameter is the medium pressure pain threshold at pre-treatment baseline (pressure that evokes a perceived pain intensity of 40-50 out of 100 on a numerical rating scale). Measured in kg/cm^2.
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: kg/cm^2
2.7333  (.83166) 2.583  (.84339)
2.Primary Outcome
Title Change in Pain Threshold From Baseline to End of Treatment.
Hide Description The primary outcome parameter is the change in medium pressure pain threshold (pressure that evokes a perceived pain intensity of 40-50 out of 100 on a numerical rating scale) from baseline to end of treatment. Measured in kg/cm^2. Lower values represent a worse outcome.
Time Frame baseline compared with 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Of 17 participants who completed both sequences, data was analyzed for the 15 whose values for all measurement variables were usable.
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: kg/cm^2
Pre-Treatment (Week 0 or 9) 2.7333  (.83166) 2.583  (.84339)
Post-Treatment (Week 6 or 15) 2.650  (1.05982) 2.70  (.99642)
3.Secondary Outcome
Title Diffuse Noxious Inhibitory Control (DNIC) Effect at Baseline.
Hide Description 0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome.
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
One participant did not complete this outcome measure.
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.134  (17.51978) 12.0240  (20.80824)
4.Secondary Outcome
Title Change in Diffuse Noxious Inhibitory Control (DNIC) Effect From Baseline to End of Treatment.
Hide Description 0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome.
Time Frame baseline compared with 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Of 17 participants who completed both sequences, data was analyzed for the 15 whose values for all measurement variables were usable. On the placebo, side one additional participant did not have data for this variable.
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 14
Mean (Standard Deviation)
Unit of Measure: units on a scale
Pre-Treatment (Week 0 or 9) 8.134  (17.51978) 12.0240  (20.80824)
Post-Treatment (Week 6 or 15) 11.0355  (17.16822) 8.50  (19.6678)
5.Secondary Outcome
Title Pain Tolerance at Baseline
Hide Description The primary outcome parameter is the pressure pain tolerance (maximum tolerated pressure) at pre-treatment baseline.
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: kg/cm^2
4.2667  (1.39983) 3.80  (1.17716)
6.Secondary Outcome
Title Change in Pain Tolerance From Baseline to End of Treatment
Hide Description The primary outcome parameter is the change in pressure pain tolerance (maximum tolerated pressure) from baseline to end of treatment. Measured in kg/cm^2. Lower values represent a worse outcome.
Time Frame baseline compared wtih 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Of 17 participants who completed both sequences, data was analyzed for the 15 whose values for all measurement variables were usable.
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description:

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

milnacipran, then placebo: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Placebo, then milnacipran: Milnacipran and placebo will be given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day.

Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: kg/cm^2
Pre-Treatment (Week 0 or 9) 4.2667  (1.39983) 3.80  (1.17716)
Post-Treatment (Week 6 or 15) 3.8667  (1.43261) 3.8667  (1.20218)
7.Other Pre-specified Outcome
Title Change in fMRI Brain Activation Patterns During Pressure Stimulation From Baseline to End of Treatment
Hide Description [Not Specified]
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Change in Descending Pain Modulation From Baseline to End of Treatment (as Assessed by Changes in fMRI Brainstem Activation Patterns)
Hide Description [Not Specified]
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later
Outcome Measure Data Not Reported
9.Other Pre-specified Outcome
Title Change in fMRI Activation Patterns During N-back Procedure From Baseline to End of Treatment.
Hide Description [Not Specified]
Time Frame Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Milnacipran Placebo
Hide Arm/Group Description Milnacipran was given orally twice daily in tablet form at different times during the course of the study. The highest dose of milnacipran to be used in the study is 200mg/day. Placebo was given orally twice daily in tablet form at different times during the course of the study.
All-Cause Mortality
Milnacipran Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Milnacipran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/20 (5.00%)      0/20 (0.00%)    
Injury, poisoning and procedural complications     
Herniated Disc  1/20 (5.00%)  1 0/20 (0.00%)  0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Milnacipran Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/20 (65.00%)      11/20 (55.00%)    
Cardiac disorders     
Tachycardia   3/20 (15.00%)  3 1/20 (5.00%)  1
Increased Blood Pressure   1/20 (5.00%)  1 1/20 (5.00%)  1
Palpitations *  1/20 (5.00%)  1 0/20 (0.00%)  0
Eye disorders     
Sensitive to Light *  1/20 (5.00%)  1 0/20 (0.00%)  0
Sore Eyes *  0/20 (0.00%)  0 1/20 (5.00%)  1
Gastrointestinal disorders     
Nausea *  5/20 (25.00%)  5 3/20 (15.00%)  3
Dry Mouth  3/20 (15.00%)  3 0/20 (0.00%)  0
Constipation *  1/20 (5.00%)  1 1/20 (5.00%)  1
Food Poisioning *  0/20 (0.00%)  0 1/20 (5.00%)  1
General disorders     
Fatigue *  1/20 (5.00%)  1 3/20 (15.00%)  3
Raw Tongue *  1/20 (5.00%)  1 0/20 (0.00%)  0
Infections and infestations     
Cough/Congestion *  1/20 (5.00%)  1 0/20 (0.00%)  0
Injury, poisoning and procedural complications     
Unable to Void *  1/20 (5.00%)  1 0/20 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back Pain *  0/20 (0.00%)  0 1/20 (5.00%)  2
Myalgia *  1/20 (5.00%)  1 2/20 (10.00%)  2
Leg Pain *  0/20 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Migraine *  1/20 (5.00%)  1 4/20 (20.00%)  4
Distrubance in Attention *  0/20 (0.00%)  0 1/20 (5.00%)  1
Headache *  1/20 (5.00%)  1 1/20 (5.00%)  1
Somnolence *  0/20 (0.00%)  0 1/20 (5.00%)  1
Psychiatric disorders     
Insomnia *  2/20 (10.00%)  2 1/20 (5.00%)  1
Anxiety *  0/20 (0.00%)  0 1/20 (5.00%)  1
Depression *  2/20 (10.00%)  3 2/20 (10.00%)  2
Emotional *  1/20 (5.00%)  1 1/20 (5.00%)  1
Vascular disorders     
Hot Flashes *  1/20 (5.00%)  1 1/20 (5.00%)  1
Flushing *  1/20 (5.00%)  1 1/20 (5.00%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Daniel Clauw, MD
Organization: University of Michigan
Phone: 734-998-6901
EMail: dclauw@med.umich.edu
Layout table for additonal information
Responsible Party: Daniel Clauw, MD, University of Michigan
ClinicalTrials.gov Identifier: NCT01173055     History of Changes
Other Study ID Numbers: MD-SAV-09
First Submitted: July 29, 2010
First Posted: July 30, 2010
Results First Submitted: August 5, 2014
Results First Posted: February 20, 2015
Last Update Posted: November 8, 2017