The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia

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. Identifier: NCT01234675
Recruitment Status : Completed
First Posted : November 4, 2010
Results First Posted : July 22, 2015
Last Update Posted : July 22, 2015
Forest Laboratories
Information provided by (Responsible Party):
Mansoor Ahmed M.D., Cleveland Sleep Research Center

Brief Summary:
Fibromyalgia is a condition of chronic widespread pain, sleep disturbance and fatigue. Most of the patients with fibromyalgia complain of either non-restorative sleep or complaints of disturbed sleep due to pain. The proposed study is aimed at examining the effects of milnacipran on sleep disturbance in patients with fibromyalgia. The study is randomized, double-blind, placebo controlled, two way crossover PSG study to explore the effects of milnacipran on sleep disturbance. Patients will receive either milnacipran 50 mg BID or matching placebo.

Condition or disease Intervention/treatment Phase
Sleep Disorders Fibromyalgia Sleep Drug: Milnacipran Phase 4

Detailed Description:

The sleep disturbance in fibromyalgia is characterized as non-restorative in nature, and is defined as a feeling of light sleep, independent of duration, and as non-refreshing. As such, these patients wake up in the morning and complain of stiffness and overall aching of the body.

It is well known that reciprocal relationship exist between sleep and pain, with sleep disturbances being an important contributor to morbidity in fibromyalgia. Milnacipran, a selective serotonin norepinephrine receptor inhibitor (SNRI)), was approved by the FDA for the management of fibromyalgia. Although milnacipran has extensively been studied in fibromyalgia patients, but there is no objective measure, i.e., the use of overnight polysomnography, to determine its effects on sleep.

The study is meant to explore the effects of milnacipran, versus placebo, on sleep in patients with fibromyalgia as measured by overnight PSGs. The study will also involve important domains of fibromyalgia etiology: sleep disturbance, pain, fatigue and quality of life.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia
Study Start Date : November 2010
Actual Primary Completion Date : February 2014
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Placebo Comparator: Placebo/milnacipran
Drug: Placebo, then milnacipran
Drug: Milnacipran
Placebo twice daily then 50 mg milnacipran or matching
Other Name: Savella

Placebo Comparator: milnacipran/placebo
Drug: milnacipran then placebo
Drug: Milnacipran
50 mg twice daily; then matching placebo twice daily
Other Name: Savella

Primary Outcome Measures :
  1. Overnight Polysomnography to Measure Sleep Disturbance With Milnacipran Treatment [ Time Frame: Overnight PSG week 5/ up to week 12; milnacipran treatment ]
    Sleep measures at week 5 of the treatment period I; and upto week 12 for treatment period II

  2. Number of Awakenings After Sleep Onset [ Time Frame: Overnight PSG week 5/ upto week 12; milnacipran treatment ]
  3. Sleep Efficiency [ Time Frame: Overnight PSG week 5/ upto week 12; milnacipran treatment ]
    Percentage of Total sleep time

  4. Arousal Index [ Time Frame: Overnight PSG week 5/ upto week 12; milnacipran treatment ]
    Number of arousal per hours

  5. Percentage of Total Sleep Time [ Time Frame: Overnight PSG week 5/ up to week 12; milnacipran treatment ]
    Sleep measures at week 5 of the treatment period I; and upto week 12 for treatment period II Percentage of Total Sleep Time that was spent in various stages of sleep

Secondary Outcome Measures :
  1. Subjective Measures With Change in Sleep and Change in Pain Measures [ Time Frame: assessments made at week 1, week 6, week 14 ]

    Subjective assessments will constitute secondary endpoints and will include:

    • Clinical Global Impression Improvement of Illness Scale (CGI-I) Clinical Global Impression- Severity of Illness scale (CGI-S); Medical Outcomes study Sleep Scale (MOS-SS); Fibromyalgia impact questionnaire (FIQ); Brief Pain Inventory (BPI) score-short form; Patient Global Impression of change (PGI-C); Beck Depression Inventory (BDI; Fatigue Severity Scale (FSS; Numeric Rating Scale-Sleep (NRS-S), part of subjective sleep questionnaire

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Men or women at least 18 years or older.
  2. Diagnosis of fibromyalgia
  3. Clinically significant sleep disturbance, defined as difficulty in maintaining sleep (WASO, and AI) at least three times per week for at least one month.
  4. Understand and willing to cooperate with the study procedures.
  5. Maintain a normal sleep schedule, with daytime-awake and nighttime-sleep schedule, with customary bedtime between 9 PM and midnight, and rise time 5 AM and 9 AM.
  6. Patients who are able to speak, read, and understand English language, and able to follow the study protocol, and are able to sign the informed consent.

Exclusion Criteria:

  1. Subject has any of the following medical conditions:

    • Liver disease; blood disorder, autoimmune disease, endocrine, cardiovascular, hypertension, renal, hepatic, gastrointestinal, or neurological disorder; Active peptic ulcer or inflammatory bowel disease.

  2. Significant sleep apnea
  3. Periodic Leg Movement or RLS
  4. Any form of severe Psychiatric illness, moderate to severe depression, including significant risk of suicide.
  5. Patients with uncontrolled glaucoma.
  6. Inability to discontinue the prohibited medications.
  7. Female of childbearing potential not using birthcontrol measures; or lactating.
  8. History of alcohol, narcotic, benzodiazepines, or other substance abuse within the past one year.
  9. Patient on prohibited Medication will include but not limited to:

    • Anxiolytics, anti-convulsants, antipsychotics, lithium, barbiturates, anti-histamines, monoamine oxidase inhibitors; or medications that affect sleep
    • Any prescription or over the counter stimulants
    • Medications that are contraindicated with the use of milnacipran
  10. Excessive caffeine use, defined as a consumption of more than 500 mg of caffeine or other xanthines, smoking >1/2 a pack/day, or alcohol use >14 units/week.
  11. History of allergy to milnacipran.

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 identifier (NCT number): NCT01234675

United States, Ohio
Cleveland Sleep Research Center
Middleburg Heights, Ohio, United States, 44130
Sponsors and Collaborators
Mansoor Ahmed M.D.
Forest Laboratories
Principal Investigator: Mansoor Ahmed, MD Cleveland Sleep Research Cneter
Study Director: Rozina Aamir, MS, MBA Cleveland Sleep Research Center
Study Director: Noel Cyrill, MD SouthWest Cleveland Sleep Center
Study Director: Nosson S Goldfarb, M.D. Cleveland Sleep Research Center

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Mansoor Ahmed M.D., Medical Director, Cleveland Sleep Research Center Identifier: NCT01234675     History of Changes
Other Study ID Numbers: SAV-MD-17
First Posted: November 4, 2010    Key Record Dates
Results First Posted: July 22, 2015
Last Update Posted: July 22, 2015
Last Verified: July 2015

Keywords provided by Mansoor Ahmed M.D., Cleveland Sleep Research Center:
Sleep disorders
Forest Laboratories

Additional relevant MeSH terms:
Myofascial Pain Syndromes
Sleep Wake Disorders
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Mental Disorders
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