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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01173055
First Posted: July 30, 2010
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Daniel Clauw, MD, University of Michigan
  Purpose
Fibromyalgia is a condition that includes pain, tenderness, stiff muscle, and fatigue. Researchers want to find out if "a drug" called milnacipran can help people with fibromyalgia. milnacipran (Savella) is approved by the FDA for the management of fibromyalgia. In this study, milnacipran will be given to find out more about how it affects pain and thinking in people with fibromyalgia.

Condition Intervention Phase
Fibromyalgia Drug: milnacipran Drug: Placebo Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Randomized, Double-blind,Placebo-controlled, Two-way Crossover Study to Evaluate the Effect of Milnacipran on Pain Processing and Functional Magnetic Resonance Imaging Activation Patterns in Patients With Fibromyalgia

Resource links provided by NLM:


Further study details as provided by Daniel Clauw, MD, University of Michigan:

Primary Outcome Measures:
  • Pain Threshold at Baseline [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment ]
    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.

  • Change in Pain Threshold From Baseline to End of Treatment. [ Time Frame: baseline compared with 6 weeks of treatment ]
    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.


Secondary Outcome Measures:
  • Diffuse Noxious Inhibitory Control (DNIC) Effect at Baseline. [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment ]
    0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome.

  • Change in Diffuse Noxious Inhibitory Control (DNIC) Effect From Baseline to End of Treatment. [ Time Frame: baseline compared with 6 weeks of treatment ]
    0-100 numerical rating scale. 0 on the numerical scale represents a better outcome. 100 represents a worse outcome.

  • Pain Tolerance at Baseline [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment ]
    The primary outcome parameter is the pressure pain tolerance (maximum tolerated pressure) at pre-treatment baseline.

  • Change in Pain Tolerance From Baseline to End of Treatment [ Time Frame: baseline compared wtih 6 weeks of treatment ]
    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.


Other Outcome Measures:
  • Change in fMRI Brain Activation Patterns During Pressure Stimulation From Baseline to End of Treatment [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later ]
  • Change in Descending Pain Modulation From Baseline to End of Treatment (as Assessed by Changes in fMRI Brainstem Activation Patterns) [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later ]
  • Change in fMRI Activation Patterns During N-back Procedure From Baseline to End of Treatment. [ Time Frame: Baselines measured at week 0 and week 9 after washout from first assignment to treatment; treatment effect measures collected 6 weeks later ]

Enrollment: 22
Study Start Date: June 2010
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Milnacipran
Milnacipran 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.
Drug: milnacipran
Milnacipran 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.
Other Name: Savella
Experimental: Placebo
Placebo will be given orally twice daily in tablet form at different times during the course of the study.
Drug: Placebo
Placebo will be given orally twice daily in tablet form at different times during the course of the study.
Other Name: placebo/sugar pill

Detailed Description:

The objective of this study is to evaluate the effect of milnacipran on pain processing in patients with fibromyalgia and to assess the correlation between this effect and neural activation patterns during functional Magnetic Resonance Imaging (fMRI).

NOTE regarding Changes in Outcome Measures

In this Crossover Study, participants were involved for approximately 16 weeks in this sequence: a week of preparing for the initial assessments, baseline measurements (Week 0), 6 weeks on placebo or study drug followed by measurements for effect of drug or placebo (Week 6); a week of titration off of drug, if appropriate (or continued placebo, if on placebo), two weeks of washout, a new baseline assessment (Week 9), six weeks of study drug (or placebo), another set of measurements for effect of drug or placebo (Week 15), and a final titration period to maintain masking of assignment to drug or placebo. Of 17 participants who completed both sequences, data was analyzed for the 15 whose values for all measurement variables were usable.

When Outcome measure data was originally and accurately posted for baseline and change after treatment, the time frames listed were 0 and 15 weeks, because the last assessment was gathered at approximately week 15 for each person whose data is in the data set. However, given the crossover design, it seems more accurate and understandable, to show the time frame for the outcome measure as 6 because the participants were each administered drug or placebo for six weeks total. (Of course for the Placebo then Study Drug arm, the placebo data was collected at week 6, and for the Study Drug then Placebo arm, the drug data was collected at week 6, and similarly for the first group the drug data was collected at week 15 (first assignment, plus 1 week titration, 2 weeks washout, new baseline at week 9, and final collection at week 15), and for the second group the placebo data was collected at week 15.

Thus, outcome measures originally listed for 6 and 9 weeks, which were previously shown as "Data Not Reported" were effectively already included within the data presented for change from baseline shown in Week 15 in this fashion: 9 week data for the second assignment is part of the "week 0 data" for the first assignment, to get pre-treatment baseline for each treatment shown. Week 6 data is the post-treatment data which was shown as week 15, but is now recategorized as 6 week data. There is no, and never was, any data that could represent assignment to drug or placebo for 9 or 15 weeks.

Additionally, several outcome measures based on fMRI values were always listed in the protocol as other outcomes (not secondary outcomes), but had been incorrectly posted in the earlier listings on ClinicalTrials.gov. They have been accurately reclassified in the 2017 resubmission.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • You may be eligible to take part in this study if the following are true:

    • You are between the age of 18 and 70 years
    • If you are female
    • If you are right handed
    • You have a diagnosis of fibromyalgia for at least 3 months, as defined by the American College of Rheumatology 1990 Criteria
    • You are willing to stop taking certain medicines that you may be taking on a regular basis. The researchers will discuss these medications with you in detail

Exclusion Criteria:

  • You may not be eligible take part in this study if any of the following are true for you:

    • You have problems with your heart or cardiovascular system
    • You have problems with your liver or kidneys
    • You have an autoimmune disease, or a whole-body infection like HIV or hepatitis
    • You have cancer
    • You are pregnant or breastfeeding
    • You abuse drugs or alcohol
    • You have suicidal thoughts or wishes
    • You have taken milnacipran or another study drug within the last 30 days
    • You have a medical problem not listed here that would make it unsafe for you to take part in the study
    • The research team feels that you will be unable to complete all phases of the study
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01173055


Locations
United States, Michigan
University of Michigan, Chronic Pain and Fatigue Research Center
Ann Arbor, Michigan, United States, 48106
Sponsors and Collaborators
University of Michigan
Forest Laboratories
Investigators
Principal Investigator: Daniel Clauw, MD University of Michigan
  More Information

Responsible Party: Daniel Clauw, MD, Daniel Clauw, Professor of Anesthesiology, University of Michigan, 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
Last Verified: October 2017

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Milnacipran
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Adrenergic Uptake Inhibitors
Adrenergic Agents