Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Completed
• CT.gov ID: NCT02785406
• Collaborator: Peter F. McManus Charitable Trust (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 30.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effectiveness of a medication called suvorexant in reducing anxiety, improving sleep, and reducing cocaine cravings or cocaine use.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Use Disorder; Anxiety	Drug: suvorexant; Drug: Placebo (for suvorexant)	Phase 2

Detailed Description

Preclinical research has established important functions for the orexin system in mediating arousal/sleep, stress, and cue-induced reinstatement of drug taking (e.g., relapse). The role of stress/anxiety and drug cue reactivity in human drug relapse is well established, but to date, the role of the orexin system in modulating these phenomena has not been examined in humans with substance use disorders (e.g., cocaine). The goal of the present first-in-human study will be to examine the effects of an orexin antagonist (suvorexant) on interactions among stress/anxiety, sleep, and drug-cue reactivity. The study will utilize a battery of highly sensitive, drug-specific, laboratory measures of drug cue reactivity (a relapse risk model), and well-established metrics of stress/anxiety and sleep. The hypothesis is that antagonism of the orexin system will attenuate the link between (1) stress/anxiety and drug cue reactivity, and (2) sleep and drug cue reactivity. These results will elucidate a unique biochemical mechanism for understanding relapse, and provide a potential medication target for relapse prevention.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Role of the Orexin Receptor System in Stress, Sleep and Cocaine Use
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: Nov 15, 2018
• Actual Study Completion Date: Nov 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: suvorexant Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Drug: suvorexant; Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.; Other Names: Belsomra
Placebo Comparator: Placebo Subjects will receive placebo once daily at 10 PM.	Drug: Placebo (for suvorexant); Subjects will receive placebo capsules once daily at 10 PM.; Other Names: corn starch

Outcome Measures

Primary Outcome Measures

1. Cue Reactivity as Assessed by the Attention Bias (AB) Task [day 0]

   The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

2. Cue Reactivity as Assessed by the Attention Bias (AB) Task [day 7]

   The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

3. Cue Reactivity as Assessed by the Attention Bias (AB) Task [day 14]

   The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.

4. Total Sleep as Assessed by the Misfit Shine Device [day 0]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

5. Total Sleep as Assessed by the Misfit Shine Device [day 2]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

6. Total Sleep as Assessed by the Misfit Shine Device [day 4]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

7. Total Sleep as Assessed by the Misfit Shine Device [day 7]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

8. Total Sleep as Assessed by the Misfit Shine Device [day 9]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

9. Total Sleep as Assessed by the Misfit Shine Device [day 11]

   Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

10. Total Sleep as Assessed by the Misfit Shine Device [day 14]

    Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.

11. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 0]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

12. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 2]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

13. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 4]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

14. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 7]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

15. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 9]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

16. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 11]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

17. Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale [day 14]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.

18. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale. [day 0]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

19. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale [day 2]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

20. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale [day 4]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

21. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale [day 7]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

22. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale [day 9]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

23. Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale [day 11]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

24. Anxiety as Assessed by the DASS21 Self-report Questionnaire [day 14]

    DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.

Secondary Outcome Measures

1. Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief [day 0, day 7, and day 14]

   The Cocaine Craving Questionnaire (CCQ) Brief is a self-report, 14-item measure with five conceptual domains: Desire to Use, Intention to Use, Anticipation of Positive Outcome, Anticipation of Relief from Dysphoria, and Lack of Control over use. The measure is well validated and has been used in multiple studies of CUD. Total score ranges from 1 to 7. A higher score indicates a worse outcome.

2. Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) [day 0, day 2, day 4, day 7, day 9, day 11, and day 14]

   The Pittsburg Sleep Quality Index (PSQI) is an 18-item self-report measure of sleep, providing a well-validated and reliable measure of sleep quality, latency, duration, duration efficiency, and disturbance, and an overall summary. The overall summary score will be reported for this measure. The PSQI has been used in several studies of individuals with SUD, including cocaine. Total score ranges from 0-21, with a higher score indicating worse outcome.

3. Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure [day 0, day 7, and day 14]

   Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis

4. Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure [day 0, day 7, and day 14]

   Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.

5. Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) [day 0, day 7, and day 14]

   Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.

6. Stress as Assessed by a Visual Analog Scale (VAS) for Stress [day 0, day 2, day 4, day 7, day 9, day 11, and day 14]

   Score provided is the total score (0 to 300) across three items that are each on a 0-100 scale. A higher score indicates greater stress.

7. Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles [day 2, day 4, day 7, day 9, day 11, and day 14]

8. Percent Medication Compliance as Assessed by Pill Counts [day 2, day 4, day 7, day 9, day 11, and day 14]

9. Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples [day 2, day 4, day 7, day 9, day 11, and day 14]

10. Percent Medication Compliance as Assessed by Text Reminders and Replies [day 2, day 4, day 7, day 9, day 11, and day 14]

    Text-based reminders to take the medication will be enabled via using a HIPAA secure texting service (Talksoft ©), used broadly in medical settings. Participants will be prompted each night at 10 PM to take their medication, and instructed to text back "yes" when they have taken their medication.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• meet current DSM-5 criteria for cocaine use disorder (CUD) of at least moderate severity (≥4 symptoms)

Exclusion Criteria:

• current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, marijuana, or nicotine

• have a DSM-IV axis I psychiatric disorder or neurological disease or disorder requiring ongoing treatment and/or making study participation unsafe

• significant current suicidal or homicidal ideation

• medical conditions contraindicating administration of suvorexant (e.g., severe pulmonary disease, severe cardiovascular disease or clinically abnormal EEG, severe liver or kidney disease, seizure disorder, or sleep disorder - particularly narcolepsy)

• taking medications known to have significant drug interactions with the study medication(s) (e.g., MAO inhibitors, anticonvulsants, haloperidol, phenothiazines, anesthetics, and all sedatives)

• currently or recently (last 3 months) treated for substance use [other than cocaine or nicotine] or another psychiatric condition

• conditions of probation or parole requiring reports of drug use to officers of the court; (8) impending incarceration

• pregnant or nursing for female patients

• inability to read, write, or speak English [required for lab tasks and psychometric scales]

• unwillingness to sign a written informed consent form

• subjects with alcohol use disorders or are drinking > 7 alcoholic drinks per week. All subjects who are excluded will be given referral information to other local treatment programs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas Health Science Center at Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston
• Peter F. McManus Charitable Trust

Investigators

• Principal Investigator: Scott D. Lane, PhD, The University of Texas Health Science Center, Houston

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 25, 2017

More Information

Publications

None provided.

• Responsible Party: Scott Lane, Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02785406
• Other Study ID Numbers: HSC-MS-16-0120
• First Posted: May 27, 2016
• Last Update Posted: Dec 11, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Scott Lane, Professor, The University of Texas Health Science Center, Houston: cocaine; sleep; anxiety; craving; addiction; orexin; cue reactivity; suvorexant; Belsomra
• Additional relevant MeSH terms: Suvorexant

Study Results

Participant Flow

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Period Title: Overall Study
STARTED	10	10
Completed First Week	10	10
Completed Second Week	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Suvorexant	Placebo	Total
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.7 (6.7)	46.6 (6.75)	45.65 (6.62)
Sex: Female, Male (Count of Participants)
Female	1 10%	4 40%	5 25%
Male	9 90%	6 60%	15 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 30%	0 0%	3 15%
Not Hispanic or Latino	7 70%	9 90%	16 80%
Unknown or Not Reported	0 0%	1 10%	1 5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 80%	8 80%	16 80%
White	2 20%	2 20%	4 20%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Cue Reactivity as Assessed by the Attention Bias (AB) Task
Description	The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.
Time Frame	day 0

Outcome Measure Data

Analysis Population Description

Data were not collected for 1 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	9
Mean (Standard Deviation) [score on a scale]	0.524 (0.0846)	0.519 (0.107)

2. Primary Outcome

Title	Cue Reactivity as Assessed by the Attention Bias (AB) Task
Description	The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.
Time Frame	day 7

Outcome Measure Data

Analysis Population Description

Data were not collected for one in the suvorexant arm and one in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	9	9
Mean (Standard Deviation) [score on a scale]	0.443 (0.0694)	0.492 (0.149)

3. Primary Outcome

Title	Cue Reactivity as Assessed by the Attention Bias (AB) Task
Description	The attention bias (AB) task is a saccade-based eye-tracking measurement, developed by the PI to assess attentional bias to drug cues. AB measures utilizing eye movements have produced moderate to robust effects for a broad class abused substances, including cocaine. The score ranges from 0 to 1. Higher scores indicate a worse outcome.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

Data were not collected for one in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	9
Mean (Standard Deviation) [score on a scale]	0.488 (0.19)	0.508 (0.0832)

4. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 0

Outcome Measure Data

Analysis Population Description

Data were not collected for one in the suvorexant arm and 5 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	9	5
Mean (Standard Deviation) [hours]	8.18 (2.17)	8.05 (2.72)

5. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 2

Outcome Measure Data

Analysis Population Description

Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	8	6
Mean (Standard Deviation) [hours]	8.66 (2.66)	7.5 (2.49)

6. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 4

Outcome Measure Data

Analysis Population Description

Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	6	6
Mean (Standard Deviation) [hours]	6.73 (2.19)	7.39 (2.23)

7. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 7

Outcome Measure Data

Analysis Population Description

Data were not collected for one in the suvorexant arm and 4 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	9	6
Mean (Standard Deviation) [hours]	6.37 (1.91)	7.5 (1.35)

8. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 9

Outcome Measure Data

Analysis Population Description

Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	8	6
Mean (Standard Deviation) [hours]	7.91 (1.38)	8.01 (1.65)

9. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 11

Outcome Measure Data

Analysis Population Description

Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	6	6
Mean (Standard Deviation) [hours]	6.93 (1.45)	7.94 (2.73)

10. Primary Outcome

Title	Total Sleep as Assessed by the Misfit Shine Device
Description	Sleep activity is monitored with a 3-axis accelerometer inside the watch device (Misfit Shine), using a general heuristic based on time and motion. The device is waterproof and worn on the wrist 24 hrs per day. Data are downloaded to smartphone via Bluetooth.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

Data were not collected for 3 in the suvorexant arm and 5 in the placebo arm.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	7	5
Mean (Standard Deviation) [hours]	6.57 (1.96)	7.56 (0.95)

11. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	4.4 (2.84)	3.8 (3.77)

12. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	3.8 (2.44)	2.5 (2.84)

13. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	2.7 (2.31)	3.1 (4.28)

14. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.7 (1.7)	2.7 (3.3)

15. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.9 (2.18)	2.3 (3.3)

16. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	2 (2.31)	2.4 (3.24)

17. Primary Outcome

Title	Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the stress subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	2.8 (2.66)	2.3 (4.11)

18. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale.
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	2.6 (1.84)	2.3 (2)

19. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.9 (2.02)	2.1 (2.28)

20. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.5 (2.12)	1.4 (1.65)

21. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 7

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.5 (2.42)	1.2 (1.48)

22. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 9

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.4 (2.32)	0.9 (1.1)

23. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 11

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	1.4 (1.9)	0.8 (1.03)

24. Primary Outcome

Title	Anxiety as Assessed by the DASS21 Self-report Questionnaire
Description	DASS21 is a 21-item self-report questionnaire assessing the severity of clinically agreed upon core depression, anxiety, and stress symptoms. It is well validated in multiple languages and countries, and has been utilized in SUD treatment and withdrawal studies. Total score on the anxiety subscale is 0 to 42, with higher scores indicating worse outcome.
Time Frame	day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
Mean (Standard Deviation) [score on a scale]	2.2 (2.49)	1.1 (1.6)

25. Secondary Outcome

Title	Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief
Description	The Cocaine Craving Questionnaire (CCQ) Brief is a self-report, 14-item measure with five conceptual domains: Desire to Use, Intention to Use, Anticipation of Positive Outcome, Anticipation of Relief from Dysphoria, and Lack of Control over use. The measure is well validated and has been used in multiple studies of CUD. Total score ranges from 1 to 7. A higher score indicates a worse outcome.
Time Frame	day 0, day 7, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0	3.61 (1.24)	2.7 (1.26)
day 7	3.01 (1.3)	2.8 (1.02)
day 14	2.92 (1.47)	2.48 (0.98)

26. Secondary Outcome

Title	Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI)
Description	The Pittsburg Sleep Quality Index (PSQI) is an 18-item self-report measure of sleep, providing a well-validated and reliable measure of sleep quality, latency, duration, duration efficiency, and disturbance, and an overall summary. The overall summary score will be reported for this measure. The PSQI has been used in several studies of individuals with SUD, including cocaine. Total score ranges from 0-21, with a higher score indicating worse outcome.
Time Frame	day 0, day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

Data were not collected for days 2, 4, 9, and 11. For days 0, 7, and 14, where number analyzed is less than 10, data were not collected for the number that are not reported.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0	7.5 (2.46)	7 (2.36)
day 7	9.38 (4.24)	6.6 (2.91)
day 14	8.2 (3.19)	4.89 (1.76)

27. Secondary Outcome

Title	Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure
Description	Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis
Time Frame	day 0, day 7, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0, immediately before CPT	125 (12.9)	120 (17.4)
day 7, immediately before CPT	126 (10.3)	125 (16.1)
day 14, immediately before CPT	128 (17.7)	121 (16.6)
day 0, immediately after CPT	123 (12.3)	113 (13.5)
day 7, immediately after CPT	122 (12.2)	132 (19.3)
day 14, immediately after CPT	120 (15.8)	120 (20)

28. Secondary Outcome

Title	Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure
Description	Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.
Time Frame	day 0, day 7, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0, immediately before CPT	84.6 (9.43)	80.7 (17.4)
day 7, immediately before CPT	84.8 (10.5)	83.6 (12)
day 14, immediately before CPT	85.4 (12.9)	81.1 (10)
day 0, immediately after CPT	82 (8.51)	72.3 (9.1)
day 7, immediately after CPT	82.6 (9.34)	87.2 (13.1)
day 14, immediately after CPT	76.3 (19.3)	80.2 (12.4)

29. Secondary Outcome

Title	Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT)
Description	Cold Pressor Test (CPT) reliably increases activity of the sympathetic nervous system and the HPA axis, and produces reliable increases in heart rate and cortisol. Subjects are requested to submerge the dominant arm up to the wrist or elbow in ice-cold water (0° to 4° C) for as long as possible with a maximum of 90 seconds. The procedure activates afferent nerves and elicits a CNS stress response. This procedure produces no lasting biological or psychological distress beyond the acute challenge period, and physiological effects return to baseline within 90 min. In fact, the CPT is used to study pain in children, and is considered a noninvasive, exempt educational experimental activity by the IRB of the University of Texas-Austin. It has been used extensively in cardiology, endocrinology, psychiatry, and psychology since 1940 as a challenge to the peripheral and central stress axis.
Time Frame	day 0, day 7, and day 14

Outcome Measure Data

Analysis Population Description

Where number analyzed is less than 10, data were not collected for the number that are not reported.

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0, immediately before CPT	553 (291)	1269 (2070)
day 7, immediately before CPT	1108 (690)	957 (1211)
day 14, immediately before CPT	532 (522)	629 (391)
day 0, immediately after CPT	582 (448)	894 (377)
day 7, immediately after CPT	873 (904)	1280 (2063)
day 14, immediately after CPT	589 (286)	1120 (770)

30. Secondary Outcome

Title	Stress as Assessed by a Visual Analog Scale (VAS) for Stress
Description	Score provided is the total score (0 to 300) across three items that are each on a 0-100 scale. A higher score indicates greater stress.
Time Frame	day 0, day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 0	192 (44.1)	138 (63)
day 2	168 (54.8)	127 (52.6)
day 4	151 (80.5)	124 (53.2)
day 7	128 (50.1)	134 (75.4)
day 9	145 (45.9)	118 (66.3)
day 11	145 (54.9)	142 (66.2)
day 14	142 (79.4)	119 (76.4)

31. Secondary Outcome

Title	Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles
Time Frame	day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 2	91.9 (0.302)	100 (0)
day 4	81.8 (0.405)	100 (0)
day 7	81.8 (0.405)	100 (0)
day 9	81.8 (0.405)	100 (0)
day 11	100 (0)	75 (0.463)
day 14	81.8 (0.405)	87.5 (0.354)

32. Secondary Outcome

Title	Percent Medication Compliance as Assessed by Pill Counts
Time Frame	day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 2	95.5 (0.151)	100 (0)
day 4	95 (0.158)	100 (0)
day 7	100 (0)	100 (0)
day 9	100 (0)	88.9 (0.333)
day 11	90 (0.316)	100 (0)
day 14	100 (0)	100 (0)

33. Secondary Outcome

Title	Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples
Time Frame	day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 2	100 (0)	100 (0)
day 4	100 (0)	89 (0.333)
day 7	100 (0)	100 (0)
day 9	100 (0)	100 (0)
day 11	90 (0.316)	100 (0)
day 14	100 (0)	100 (0)

34. Secondary Outcome

Title	Percent Medication Compliance as Assessed by Text Reminders and Replies
Description	Text-based reminders to take the medication will be enabled via using a HIPAA secure texting service (Talksoft ©), used broadly in medical settings. Participants will be prompted each night at 10 PM to take their medication, and instructed to text back "yes" when they have taken their medication.
Time Frame	day 2, day 4, day 7, day 9, day 11, and day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Suvorexant	Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.	Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
Measure Participants	10	10
day 2	55.6 (0.527)	100 (0)
day 4	55.6 (0.527)	87.5 (0.354)
day 7	70 (0.483)	100 (0)
day 9	70 (0.483)	100 (0)
day 11	90 (0.316)	75 (0.463)
day 14	87.5 (0.354)	75 (0.463)

Adverse Events

Time Frame	14 days
Arm/Group Title	Suvorexant		Placebo
Arm/Group Description	Subjects will receive suvorexant (10 mg week 1, 20 mg week 2), once daily at 10 PM. suvorexant: Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.		Subjects will receive placebo once daily at 10 PM. Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM.
All Cause Mortality
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Suvorexant		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.