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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02785406
Recruitment Status : Completed
First Posted : May 27, 2016
Results First Posted : December 11, 2019
Last Update Posted : December 11, 2019
Sponsor:
Collaborator:
Peter F. McManus Charitable Trust
Information provided by (Responsible Party):
Scott Lane, The University of Texas Health Science Center, Houston

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.

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Study Type : Interventional  (Clinical Trial)
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 2016
Actual Primary Completion Date : November 15, 2018
Actual Study Completion Date : November 15, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety
Drug Information available for: Suvorexant

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 Name: 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 Name: corn starch




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02785406


Locations
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United States, Texas
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
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Principal Investigator: Scott D. Lane, PhD The University of Texas Health Science Center, Houston
  Study Documents (Full-Text)

Documents provided by Scott Lane, The University of Texas Health Science Center, Houston:
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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    Key Record Dates
Results First Posted: December 11, 2019
Last Update Posted: December 11, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Scott Lane, The University of Texas Health Science Center, Houston:
cocaine
sleep
anxiety
craving
addiction
orexin
cue reactivity
suvorexant
Belsomra
Additional relevant MeSH terms:
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Suvorexant
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Orexin Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action