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Completed

NCT Number: NCT02785406

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

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.

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Key information

Age range

19 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Suvorexant

Drug

Subjects will receive suvorexant capsules (10 mg week 1, 20 mg week 2), once daily at 10 PM.

Other names: Belsomra

Placebo (for suvorexant)

Drug

Subjects will receive placebo capsules once daily at 10 PM.

Other names: corn starch

Primary outcomes

  1. Cue Reactivity as Assessed by the Attention Bias (AB) Task

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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 outcomes

  1. Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) Brief

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: day 2, day 4, day 7, day 9, day 11, and day 14

  8. Percent Medication Compliance as Assessed by Pill Counts

    Time frame: 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

    Time frame: day 2, day 4, day 7, day 9, day 11, and day 14

  10. Percent Medication Compliance as Assessed by Text Reminders and Replies

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

The University of Texas Health Science Center, Houston

Other

Collaborators

  • Peter McManus Charitable Trust

Registry information

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
May 27, 2016
Registry last updated
Dec 11, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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