Clinical trial NCT02684136: Suvorexant in Insomnia Co-morbid With Fibromyalgia
Official title: A Double-blind, Crossover, Study to Compare the Hypnotic, Daytime Sleepiness/Fatigue, and Pain Effects of Nighttime Administration of Suvorexant 20 mg Versus Placebo in Patients With Fibromyalgia and Comorbid Insomnia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Insomnia
Fibromyalgia
Keywords: insomnia
fibromyalgia
polysomnography
pain management
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 10
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will compare sleep, pain and daytime sleepiness/fatigue in people with insomnia co-morbid with fibromyalgia while treated short-term with suvorexant 20 mg versus placebo.

Detailed description: It has now become clear that the relation of sleep and pain is bidirectional; acute and chronic pain is associated with disturbed sleep and disturbed sleep enhances pain. Experimental studies have shown that reduced and fragmented sleep in pain-free normals increases their pain sensitivity and daily self-report studies in chronic pain patients have shown a poor night of sleep is followed by enhanced next-day pain. In mediation analyses of large clinical data sets it is found that the sleep-pain side of the bidirectional relation, as opposed to the pain-sleep side, accounts for the greater variance. These data then would suggest that improving sleep in chronic pain disorders should attenuate daytime pain.

Most of the drugs used to treat chronic pain facilitate inhibitory central nervous system mechanisms as their primary mechanism of action. Suvorexant, recently approved by the FDA for the treatment of insomnia characterized by difficulties with sleep onset and sleep maintenance, has a unique mechanism of action. Suvorexant is a selective antagonist for orexin receptors (OX1R and OX2R). Orexins are considered to be involved in arousal and maintenance of the waking state.

As such, suvorexant may provide unique clinical benefit as a treatment in chronic pain conditions with co-morbid insomnia, and specifically for fibromyalgia with its putative central hyperarousal and hypersensitization. Thus, this project proposes to study objective and clinical measures of sleep, pain, and daytime sleepiness and fatigue in patients with fibromyalgia and co-morbid insomnia while treated short-term with suvorexant 20 mg versus placebo.

Those qualifying will receive suvorexant 20 mg and placebo for each of 9 nights in a cross over design with 7 nights of washout between treatments. Overnight sleep recordings (PSGs) will be collected on nights 7 and 8 of each crossover treatment arm to determine objective sleep measures. During the day following night 7 in each arm, a Multiple Sleep Latency Test (MSLT) at 1000, 1200, 1400, and 1600 hr will be conducted and nociceptive sensitivity \[finger withdrawal latency (FWL)\] testing to a radiant heat stimulus (1100 and 1500 hr) will be conducted on day 1 and day 8. Self-reported mood and pain indices will also be completed prior to each FWL test.

Primary outcomes to be measured include PSG sleep efficacy and FWL response on both conditions (suvorexant 20 mg versus placebo).

Eligibility criteria: Inclusion Criteria:

* meet Diagnostic and Statistical Manual 5th ed criteria for insomnia
* meet American College of Rheumatology criteria for fibromyalgia
* otherwise good psychiatric and stable physical health

Exclusion Criteria:

* other primary sleep disorders
* pain symptoms unrelated to fibromyalgia
* current pregnancy or breast-feeding

Primary outcomes:
measure: Polysomnographic Assessment of Sleep
timeFrame: continuous sleep recording from 11pm to 7am on night 8
Secondary outcomes:
measure: Daytime Pain Sensitivity
timeFrame: mean of tests at 1100 and 1500 hrs on both day 1 and day 8
Other outcomes:
Locations:
city: Detroit
country: United States
facility: HFHS Sleep Disorders Ctr
state: Michigan
Study officials:
affiliation: Henry Ford Health System
name: Timothy Roehrs, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health System
name: Thomas Roth, PhD
role: STUDY_CHAIR
References:
citation: Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
citation: Roehrs T, Diederichs C, Gillis M, Burger AJ, Stout RA, Lumley MA, Roth T. Nocturnal sleep, daytime sleepiness and fatigue in fibromyalgia patients compared to rheumatoid arthritis patients and healthy controls: a preliminary study. Sleep Med. 2013 Jan;14(1):109-15. doi: 10.1016/j.sleep.2012.09.020. Epub 2012 Nov 11.
citation: Roehrs T, Withrow D, Koshorek G, Verkler J, Bazan L, Roth T. Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo. J Clin Sleep Med. 2020 Mar 15;16(3):415-421. doi: 10.5664/jcsm.8220. Epub 2020 Jan 14.