The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia

Mansoor Ahmed M.D.

Status and phase: Completed; Phase 4

Conditions: Sleep Disorders; Fibromyalgia; Sleep

Treatments: Drug: Placebo; Drug: Milnacipran

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01234675

SAV-MD-17

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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19 participants in 2 patient groups, including a placebo group

milnacipran

Experimental group

Description:

Drug: milnacipran 7-day dose escalation, 28- day treatment with milnacipran 50 mg and 7-day taper period before or after crossover to placebo

Treatment:

Drug: Milnacipran

placebo

Placebo Comparator group

Description:

Drug: placebo 45-day placebo treatment before or after crossover to milnacipran

Treatment:

Drug: Placebo