Examination of the Effectiveness of Suvorexant in Improving Daytime Sleep in Shift Workers

• Sponsor: VA Palo Alto Health Care System (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT02491788
• Collaborator: Merck Sharp & Dohme LLC (Industry), Stanford University (Other)
• Enrollment: 19
• Location: 1
• Arms: 2
• Actual Duration (Months): 42
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to test the hypothesis that ingestion of the wake-inhibiting drug suvorexant 30 minutes prior to daytime sleep initiation in individuals working overnight shifts will significantly improve both objective (total sleep time, sleep efficiency, wake after sleep onset) and subjective (sleep quality) measures of daytime sleep.

Condition or Disease	Intervention/Treatment	Phase
Sleep Disorder, Shift-Work	Drug: Suvorexant; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Aug 1, 2019
• Actual Study Completion Date: Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug 10 mg of suvorexant 30 minutes prior to daytime sleep opportunity	Drug: Suvorexant; Other Names: Belsomra
Placebo Comparator: Placebo Placebo pill 30 minutes prior to daytime sleep opportunity	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Change in Average Total Sleep Time [Daytime sleep will be examined from baseline to after 3 weeks]

   Change in average of the total amount of sleep occurring during daytime sleep episodes following night shift work, as compared to baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 20-60 (older individuals excluded due to altered sleep-related circadian signaling)

• Males and females

• Shift worker

• Minimum of three months of prior shift work

• Will work minimum of four nights per week or 32 hours of night shift per week during study

• "Night work" defined as having at least six hours of work occurring between 8 PM and 8 AM and no longer than 12 hours on shift

• Presence of DSM-5 defined Circadian Rhythm Sleep-Wake Disorder: Shift Work Type

• Insomnia (SE < 88%) during attempted daytime sleep or excessive sleepiness during nocturnal wake

Exclusion Criteria:

• Currently or planning to become pregnant

• Currently breastfeeding

• Inadequate opportunity (<7 hours) for daytime sleep after shift work

• Use of sleep aids during the study period. Includes as needed or continuous use of prescription, non-prescription, and naturopathic pharmacotherapies

• Diagnosis or detection (during study) of sleep disordered breathing (AHI>10) on home sleep testing; referral to clinical sleep program will be offered

• Diagnosis of narcolepsy

• Restless Legs Syndrome

• 600 mg caffeine intake per night shift or use of prescription stimulant medication during night shift

• Rotational or irregular work shifts during study

• Use of digoxin for six months prior to or during study

• Use of strong (e.g., etoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, conivaptan) or moderate (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil) CYP3A inhibitors or CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin) for six months prior to or during study

• Severe hepatic impairment

• Unstable or severe medical or psychiatric condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Palo Alto Health Care System	Palo Alto	California	United States	94304

Sponsors and Collaborators

• VA Palo Alto Health Care System
• Merck Sharp & Dohme LLC
• Stanford University

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 21, 2015

More Information

Publications

None provided.

• Responsible Party: Jamie M. Zeitzer, Ph.D., Associate Professor, VA Palo Alto Health Care System
• ClinicalTrials.gov Identifier: NCT02491788
• Other Study ID Numbers: IRB-34778
• First Posted: Jul 8, 2015
• Last Update Posted: Jul 1, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Sleep Wake Disorders; Sleep Disorders, Circadian Rhythm; Suvorexant

Study Results

Participant Flow

Arm/Group Title	Drug	Placebo
Arm/Group Description	10+ mg of suvorexant 30 minutes prior to daytime sleep opportunity Suvorexant	Placebo pill 30 minutes prior to daytime sleep opportunity Placebo
Period Title: Overall Study
STARTED	8	11
COMPLETED	8	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Drug	Placebo	Total
Arm/Group Description	10 mg of suvorexant 30 minutes prior to daytime sleep opportunity Suvorexant	Placebo pill 30 minutes prior to daytime sleep opportunity Placebo	Total of all reporting groups
Overall Participants	8	11	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	11 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.4 (12.9)	35.1 (9.33)	37.7 (11.1)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	3 27.3%	6 31.6%
Male	5 62.5%	8 72.7%	13 68.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	3 27.3%	3 15.8%
Native Hawaiian or Other Pacific Islander	0 0%	1 9.1%	1 5.3%
Black or African American	1 12.5%	1 9.1%	2 10.5%
White	5 62.5%	5 45.5%	10 52.6%
More than one race	1 12.5%	0 0%	1 5.3%
Unknown or Not Reported	1 12.5%	1 9.1%	2 10.5%
Region of Enrollment (participants) [Number]
United States	8 100%	11 100%	19 100%

Outcome Measures

1. Primary Outcome

Title	Change in Average Total Sleep Time
Description	Change in average of the total amount of sleep occurring during daytime sleep episodes following night shift work, as compared to baseline
Time Frame	Daytime sleep will be examined from baseline to after 3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Drug	Placebo
Arm/Group Description	10+ mg of suvorexant 30 minutes prior to daytime sleep opportunity Suvorexant	Placebo pill 30 minutes prior to daytime sleep opportunity Placebo
Measure Participants	8	11
Mean (Standard Error) [hours/sleep opportunity]	1.83 (0.62)	-0.33 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Drug, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.16
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.75
	Estimation Comments

Adverse Events

Time Frame	5 weeks
Adverse Event Reporting Description	Weekly and ad libitum telephone assessment with project coordinator
Arm/Group Title	Drug		Placebo
Arm/Group Description	10+ mg of suvorexant 30 minutes prior to daytime sleep opportunity Suvorexant		Placebo pill 30 minutes prior to daytime sleep opportunity Placebo
All Cause Mortality
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/11 (0%)
Serious Adverse Events
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Drug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		2/11 (18.2%)
Musculoskeletal and connective tissue disorders
Facial swelling	0/8 (0%)	0	1/11 (9.1%)	1
Nervous system disorders
Fatigue	0/8 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.