Anxiety, Cocaine Use Disorder
Conditions
Keywords
cocaine, sleep, anxiety, craving, addiction, orexin, cue reactivity, suvorexant, Belsomra
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.
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.
Interventions
DRUGsuvorexant
Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.
DRUGPlacebo (for suvorexant)
Subjects will receive placebo capsules once daily at 10 PM.
Sponsors
Peter McManus Charitable Trust
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Percent Medication Compliance as Assessed by Pill Counts | day 2, day 4, day 7, day 9, day 11, and day 14 | — |
| 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. |
| 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. |
| 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 | — |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Suvorexant 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. | 10 |
| Placebo Subjects will receive placebo once daily at 10 PM.
Placebo (for suvorexant): Subjects will receive placebo capsules once daily at 10 PM. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Suvorexant | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 44.7 years STANDARD_DEVIATION 6.7 | 45.65 years STANDARD_DEVIATION 6.62 | 46.6 years STANDARD_DEVIATION 6.75 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 16 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 16 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment United States | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 9 Participants | 15 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire | 2.2 score on a scale | Standard Deviation 2.49 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire | 1.1 score on a scale | Standard Deviation 1.6 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.9 score on a scale | Standard Deviation 2.02 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 2.1 score on a scale | Standard Deviation 2.28 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.5 score on a scale | Standard Deviation 2.12 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.4 score on a scale | Standard Deviation 1.65 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.4 score on a scale | Standard Deviation 1.9 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 0.8 score on a scale | Standard Deviation 1.03 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.4 score on a scale | Standard Deviation 2.32 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 0.9 score on a scale | Standard Deviation 1.1 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.5 score on a scale | Standard Deviation 2.42 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale | 1.2 score on a scale | Standard Deviation 1.48 |
Primary
Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale.
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale. | 2.6 score on a scale | Standard Deviation 1.84 |
| Placebo | Anxiety as Assessed by the DASS21 Self-report Questionnaire Anxiety Subscale. | 2.3 score on a scale | Standard Deviation 2 |
Primary
Cue Reactivity as Assessed by the Attention Bias (AB) Task
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
Population: Data were not collected for 1 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.524 score on a scale | Standard Deviation 0.0846 |
| Placebo | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.519 score on a scale | Standard Deviation 0.107 |
Primary
Cue Reactivity as Assessed by the Attention Bias (AB) Task
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
Population: Data were not collected for one in the suvorexant arm and one in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.443 score on a scale | Standard Deviation 0.0694 |
| Placebo | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.492 score on a scale | Standard Deviation 0.149 |
Primary
Cue Reactivity as Assessed by the Attention Bias (AB) Task
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
Population: Data were not collected for one in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.488 score on a scale | Standard Deviation 0.19 |
| Placebo | Cue Reactivity as Assessed by the Attention Bias (AB) Task | 0.508 score on a scale | Standard Deviation 0.0832 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 3.8 score on a scale | Standard Deviation 2.44 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.5 score on a scale | Standard Deviation 2.84 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.7 score on a scale | Standard Deviation 2.31 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 3.1 score on a scale | Standard Deviation 4.28 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 1.7 score on a scale | Standard Deviation 1.7 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.7 score on a scale | Standard Deviation 3.3 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 1.9 score on a scale | Standard Deviation 2.18 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.3 score on a scale | Standard Deviation 3.3 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2 score on a scale | Standard Deviation 2.31 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.4 score on a scale | Standard Deviation 3.24 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 4.4 score on a scale | Standard Deviation 2.84 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 3.8 score on a scale | Standard Deviation 3.77 |
Primary
Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.8 score on a scale | Standard Deviation 2.66 |
| Placebo | Stress as Assessed by the DASS21 Self-report Questionnaire Stress Subscale | 2.3 score on a scale | Standard Deviation 4.11 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 8.66 hours | Standard Deviation 2.66 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 7.5 hours | Standard Deviation 2.49 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for 3 in the suvorexant arm and 5 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 6.57 hours | Standard Deviation 1.96 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 7.56 hours | Standard Deviation 0.95 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 6.93 hours | Standard Deviation 1.45 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 7.94 hours | Standard Deviation 2.73 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for 2 in the suvorexant arm and 4 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 7.91 hours | Standard Deviation 1.38 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 8.01 hours | Standard Deviation 1.65 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for one in the suvorexant arm and 4 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 6.37 hours | Standard Deviation 1.91 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 7.5 hours | Standard Deviation 1.35 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for 4 in the suvorexant arm and 4 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 6.73 hours | Standard Deviation 2.19 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 7.39 hours | Standard Deviation 2.23 |
Primary
Total Sleep as Assessed by the Misfit Shine Device
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
Population: Data were not collected for one in the suvorexant arm and 5 in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Suvorexant | Total Sleep as Assessed by the Misfit Shine Device | 8.18 hours | Standard Deviation 2.17 |
| Placebo | Total Sleep as Assessed by the Misfit Shine Device | 8.05 hours | Standard Deviation 2.72 |
Secondary
Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 0 | 3.61 score on a scale | Standard Deviation 1.24 |
| Suvorexant | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 7 | 3.01 score on a scale | Standard Deviation 1.3 |
| Suvorexant | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 14 | 2.92 score on a scale | Standard Deviation 1.47 |
| Placebo | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 0 | 2.7 score on a scale | Standard Deviation 1.26 |
| Placebo | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 7 | 2.8 score on a scale | Standard Deviation 1.02 |
| Placebo | Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief | day 14 | 2.48 score on a scale | Standard Deviation 0.98 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 2 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 4 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 7 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 9 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 11 | 90 percent medication compliance | Standard Deviation 0.316 |
| Suvorexant | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 14 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 11 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 2 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 9 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 4 | 89 percent medication compliance | Standard Deviation 0.333 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 14 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Analysis of Riboflavin Markers in Urine Samples | day 7 | 100 percent medication compliance | Standard Deviation 0 |
Secondary
Percent Medication Compliance as Assessed by Pill Counts
Time frame: day 2, day 4, day 7, day 9, day 11, and day 14
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 9 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 4 | 95 percent medication compliance | Standard Deviation 0.158 |
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 11 | 90 percent medication compliance | Standard Deviation 0.316 |
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 2 | 95.5 percent medication compliance | Standard Deviation 0.151 |
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 14 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by Pill Counts | day 7 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 14 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 2 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 4 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 9 | 88.9 percent medication compliance | Standard Deviation 0.333 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 11 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Pill Counts | day 7 | 100 percent medication compliance | Standard Deviation 0 |
Secondary
Percent Medication Compliance as Assessed by Text Reminders and Replies
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 2 | 55.6 percent medication compliance | Standard Deviation 0.527 |
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 4 | 55.6 percent medication compliance | Standard Deviation 0.527 |
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 7 | 70 percent medication compliance | Standard Deviation 0.483 |
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 9 | 70 percent medication compliance | Standard Deviation 0.483 |
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 11 | 90 percent medication compliance | Standard Deviation 0.316 |
| Suvorexant | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 14 | 87.5 percent medication compliance | Standard Deviation 0.354 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 11 | 75 percent medication compliance | Standard Deviation 0.463 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 2 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 9 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 4 | 87.5 percent medication compliance | Standard Deviation 0.354 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 14 | 75 percent medication compliance | Standard Deviation 0.463 |
| Placebo | Percent Medication Compliance as Assessed by Text Reminders and Replies | day 7 | 100 percent medication compliance | Standard Deviation 0 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 2 | 91.9 percent medication compliance | Standard Deviation 0.302 |
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 4 | 81.8 percent medication compliance | Standard Deviation 0.405 |
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 7 | 81.8 percent medication compliance | Standard Deviation 0.405 |
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 9 | 81.8 percent medication compliance | Standard Deviation 0.405 |
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 11 | 100 percent medication compliance | Standard Deviation 0 |
| Suvorexant | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 14 | 81.8 percent medication compliance | Standard Deviation 0.405 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 11 | 75 percent medication compliance | Standard Deviation 0.463 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 2 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 9 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 4 | 100 percent medication compliance | Standard Deviation 0 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 14 | 87.5 percent medication compliance | Standard Deviation 0.354 |
| Placebo | Percent Medication Compliance as Assessed by the Medical Event Monitoring System (MEMS, Aprex Corporation) Bottles | day 7 | 100 percent medication compliance | Standard Deviation 0 |
Secondary
Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 0 | 7.5 score on a scale | Standard Deviation 2.46 |
| Suvorexant | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 7 | 9.38 score on a scale | Standard Deviation 4.24 |
| Suvorexant | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 14 | 8.2 score on a scale | Standard Deviation 3.19 |
| Placebo | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 0 | 7 score on a scale | Standard Deviation 2.36 |
| Placebo | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 7 | 6.6 score on a scale | Standard Deviation 2.91 |
| Placebo | Sleep Quality as by the Pittsburg Sleep Quality Index (PSQI) | day 14 | 4.89 score on a scale | Standard Deviation 1.76 |
Secondary
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 0, immediately before CPT | 84.6 millimeters of mercury (mmHg) | Standard Deviation 9.43 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 7, immediately before CPT | 84.8 millimeters of mercury (mmHg) | Standard Deviation 10.5 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 14, immediately before CPT | 85.4 millimeters of mercury (mmHg) | Standard Deviation 12.9 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 0, immediately after CPT | 82 millimeters of mercury (mmHg) | Standard Deviation 8.51 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 7, immediately after CPT | 82.6 millimeters of mercury (mmHg) | Standard Deviation 9.34 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 14, immediately after CPT | 76.3 millimeters of mercury (mmHg) | Standard Deviation 19.3 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 7, immediately after CPT | 87.2 millimeters of mercury (mmHg) | Standard Deviation 13.1 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 0, immediately before CPT | 80.7 millimeters of mercury (mmHg) | Standard Deviation 17.4 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 0, immediately after CPT | 72.3 millimeters of mercury (mmHg) | Standard Deviation 9.1 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 7, immediately before CPT | 83.6 millimeters of mercury (mmHg) | Standard Deviation 12 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 14, immediately after CPT | 80.2 millimeters of mercury (mmHg) | Standard Deviation 12.4 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Diastolic Blood Pressure | day 14, immediately before CPT | 81.1 millimeters of mercury (mmHg) | Standard Deviation 10 |
Secondary
Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 0, immediately before CPT | 125 millimeters of mercury (mmHg) | Standard Deviation 12.9 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 7, immediately before CPT | 126 millimeters of mercury (mmHg) | Standard Deviation 10.3 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 14, immediately before CPT | 128 millimeters of mercury (mmHg) | Standard Deviation 17.7 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 0, immediately after CPT | 123 millimeters of mercury (mmHg) | Standard Deviation 12.3 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 7, immediately after CPT | 122 millimeters of mercury (mmHg) | Standard Deviation 12.2 |
| Suvorexant | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 14, immediately after CPT | 120 millimeters of mercury (mmHg) | Standard Deviation 15.8 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 7, immediately after CPT | 132 millimeters of mercury (mmHg) | Standard Deviation 19.3 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 0, immediately before CPT | 120 millimeters of mercury (mmHg) | Standard Deviation 17.4 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 0, immediately after CPT | 113 millimeters of mercury (mmHg) | Standard Deviation 13.5 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 7, immediately before CPT | 125 millimeters of mercury (mmHg) | Standard Deviation 16.1 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 14, immediately after CPT | 120 millimeters of mercury (mmHg) | Standard Deviation 20 |
| Placebo | Stress/Anxiety as Assessed by Blood Pressure During the Cold Pressor Test (CPT) - Systolic Blood Pressure | day 14, immediately before CPT | 121 millimeters of mercury (mmHg) | Standard Deviation 16.6 |
Secondary
Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT)
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
Population: Where number analyzed is less than 10, data were not collected for the number that are not reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 0, immediately before CPT | 553 pg/mL | Standard Deviation 291 |
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 7, immediately before CPT | 1108 pg/mL | Standard Deviation 690 |
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 14, immediately before CPT | 532 pg/mL | Standard Deviation 522 |
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 0, immediately after CPT | 582 pg/mL | Standard Deviation 448 |
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 7, immediately after CPT | 873 pg/mL | Standard Deviation 904 |
| Suvorexant | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 14, immediately after CPT | 589 pg/mL | Standard Deviation 286 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 7, immediately after CPT | 1280 pg/mL | Standard Deviation 2063 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 0, immediately before CPT | 1269 pg/mL | Standard Deviation 2070 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 0, immediately after CPT | 894 pg/mL | Standard Deviation 377 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 7, immediately before CPT | 957 pg/mL | Standard Deviation 1211 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 14, immediately after CPT | 1120 pg/mL | Standard Deviation 770 |
| Placebo | Stress/Anxiety as Assessed by Cortisol Level During the Cold Pressor Test (CPT) | day 14, immediately before CPT | 629 pg/mL | Standard Deviation 391 |
Secondary
Stress as Assessed by a Visual Analog Scale (VAS) for Stress
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 4 | 151 units on a scale | Standard Deviation 80.5 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 9 | 145 units on a scale | Standard Deviation 45.9 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 2 | 168 units on a scale | Standard Deviation 54.8 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 11 | 145 units on a scale | Standard Deviation 54.9 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 7 | 128 units on a scale | Standard Deviation 50.1 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 14 | 142 units on a scale | Standard Deviation 79.4 |
| Suvorexant | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 0 | 192 units on a scale | Standard Deviation 44.1 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 14 | 119 units on a scale | Standard Deviation 76.4 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 0 | 138 units on a scale | Standard Deviation 63 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 2 | 127 units on a scale | Standard Deviation 52.6 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 4 | 124 units on a scale | Standard Deviation 53.2 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 7 | 134 units on a scale | Standard Deviation 75.4 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 9 | 118 units on a scale | Standard Deviation 66.3 |
| Placebo | Stress as Assessed by a Visual Analog Scale (VAS) for Stress | day 11 | 142 units on a scale | Standard Deviation 66.2 |