Clinical trial NCT01234675: The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia
Official title: The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sleep Disorders
Fibromyalgia
Sleep
Keywords: Fibromyalgia
Sleep disorders
Forest Laboratories
Milnacipran
Lead sponsor: Cleveland Sleep Research Center
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2010-11-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 study aimed at examining the effects of milnacipran on sleep disturbance in patients with fibromyalgia. The study is a randomized, double-blind, placebo controlled, two way crossover polysomnography (PSG) study to explore the effects of milnacipran on sleep disturbance. Patients received either milnacipran 50 mg twice a day (BID) or matching placebo.

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 exists 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 Food and Drug Administration (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 was undertaken to evaluate the effects of milnacipran on PSG determined measures of sleep in patients with fibromyalgia. The study also evaluated the impact of milnacipran on subjective measures of sleep and fibromyalgia symptoms.

Eligibility criteria: 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 (wake after sleep onset and arousal index) 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 disorder (PLMD) or restless legs syndrome (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 birth control 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.

Primary outcomes:
measure: Number of Awakenings After Sleep Onset (NAASO)
timeFrame: 4-Week maintenance treatment with milnacipran and placebo
measure: Sleep Efficiency (SE)
timeFrame: 4-Week maintenance treatment with milnacipran and placebo
measure: Wake After Sleep Onset (WASO)
timeFrame: 4-Week maintenance treatment with milnacipran and placebo
Secondary outcomes:
measure: Latency to Persistent Sleep Onset (LPS)
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Total Sleep Time (TST)
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Arousal Index (AI)
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Slow Wave Sleep (SWS)
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Sleep Quality Scale
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Fatigue Severity Scale (FSS) Total Score
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Fibromyalgia Impact Questionnaire (FIQ) Total Score
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Brief Pain Inventory (BPI) Mean Severity Score
timeFrame: 4-Week treatment with milnacipran and placebo
measure: Brief Pain Inventory (BPI) Mean Interference Score
timeFrame: 4-Week treatment with milnacipran and placebo
Other outcomes:
Locations:
city: Middleburg Heights
country: United States
facility: Cleveland Sleep Research Center
state: Ohio
Study officials:
affiliation: Cleveland Sleep Research Cneter
name: Mansoor Ahmed, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Sleep Research Center
name: Rozina Aamir, MS, MBA
role: STUDY_DIRECTOR
affiliation: SouthWest Cleveland Sleep Center
name: Noel Cyrill, MD
role: STUDY_DIRECTOR
affiliation: Cleveland Sleep Research Center
name: Nosson S Goldfarb, M.D.
role: STUDY_DIRECTOR
References:
citation: Ahmed M, Aamir R, Jishi Z, Scharf MB. The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study. J Clin Sleep Med. 2016 Jan;12(1):79-86. doi: 10.5664/jcsm.5400.