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

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ClinicalTrials.gov Identifier: NCT02785406
Recruitment Status : Recruiting
First Posted : May 27, 2016
Last Update Posted : November 30, 2017
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 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
Estimated Primary Completion Date : August 1, 2018
Estimated Study Completion Date : August 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

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.

  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.

  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.

  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 [ 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.

  12. Stress as Assessed by the DASS21 Self-report Questionnaire [ 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.

  13. Stress as Assessed by the DASS21 Self-report Questionnaire [ 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.

  14. Stress as Assessed by the DASS21 Self-report Questionnaire [ 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.

  15. Stress as Assessed by the DASS21 Self-report Questionnaire [ 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.

  16. Stress as Assessed by the DASS21 Self-report Questionnaire [ 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.

  17. Stress 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.

  18. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  19. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  20. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  21. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  22. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  23. Anxiety as Assessed by the DASS21 Self-report Questionnaire [ 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.

  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.


Secondary Outcome Measures :
  1. Cue Reactivity as Assessed by the Cocaine Craving Questionnaire (CCQ) [ Time Frame: day 0, day 7, and day 14 ]
    The Cocaine Craving Questionnaire (CCQ) 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.

  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

  3. Stress/Anxiety as Assessed by Blood Pressure 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

  4. 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.

  5. 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 ]
    A Visual Analog Scale (VAS) for stress ranks the current stress level is on a 0 - 10 visual analog scale (0 = no stress, 10 = extreme stress) cued by the question "Please rate your current stress level."

  6. 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 ]
  7. Medication Compliance as Assessed by Pill Counts [ Time Frame: day 2, day 4, day 7, day 9, day 11, and day 14 ]
  8. 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 ]
  9. 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

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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


Contacts
Contact: Scott D Lane, PhD 713-486-2535 Scott.D.Lane@uth.tmc.edu
Contact: Rolanda R Johnson, MA 713-486-2823 Rolanda.Johnson@uth.tmc.edu

Locations
United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Scott D Lane, PhD    713-486-2535    Scott.D.Lane@uth.tmc.edu   
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Peter F. McManus Charitable Trust

Responsible Party: Scott Lane, Professor, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02785406     History of Changes
Other Study ID Numbers: HSC-MS-16-0120
First Posted: May 27, 2016    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: November 2017
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:
Cocaine
Suvorexant
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Orexin Receptor Antagonists