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Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

Primary Purpose

Opioid-use Disorder, Sleep

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Suvorexant

Suvorexant Placebo

About this trial

This is an interventional basic science trial for Opioid-use Disorder

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18-70 years old
Males and non-pregnant females who agree to medically accepted birth control for the duration of the study
Meet DSM-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications [see below])
Must complete opioid detoxification (days 1-4 on the inpatient unit)

Exclusion Criteria:

Body mass index >38
Acute/unstable illness: conditions making it unsafe for participation, conditions with potential to disturb sleep (i.e. acute pain, respiratory infection)
Chronic illnesses; renal failure, liver disease, seizures, and dementing illnesses
Current psychiatric disease: psychosis, bipolar disorder, PTSD
Smoking during the night (11pm-7am). Nicotine replacement therapy is allowed
Medications including anxiolytics, hypnotics (both prescription and OTC), sedating antidepressants, anticonvulsants, sedating H1 antihistamines (non-sedating second generation H4 antihistamines are allowed), systemic steroids, respiratory stimulants and decongestants, prescription and OTC stimulants, prescription and OTC diet aids, herbal preparations, and narcotic analgesics. All medications and doses will be documented
Sleep-disordered breathing and periodic leg movements (PLMs) defined as ≥ 10 apnea-hypopneas or PLM events related to EEG arousal per hour of sleep time, or any other primary sleep (e.g. narcolepsy, restless legs syndrome) or circadian disorder
Night-shift work, which would alter circadian rhythm and be a confound in this trial.

Sites / Locations

Wayne State UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Suvorexant placebo

Suvorexant 20mg

Arm Description

Placebo (inert) tablet

Suvorexant 20mg tablet

Outcomes

Primary Outcome Measures

Opioid abstinence

Percentage of opioid-free urine drug screens (UDS)

Sleep efficiency

Sleep efficiency equals sleep time (determined by standardized scoring of electroencephalogram recordings) divided by time in bed

Secondary Outcome Measures

Daily sleep questionnaire

Morning (post-awakening) assessment of sleep quality

Actigraphic assessment of sleep

Actigraphic assessment of motion (activity counts), measured with Actiwatch and scoring software; motion is absent during sleep.

Weekly sleep questionnaire

Retrospective (past-week) self-report of sleep quality on each of 4 outpatient weeks

Timeline followback interview assessment of substance use

Percentage of outpatient weeks with substance use (opioids, methadone, buprenorphine, cocaine metabolites, benzodiazepines, barbiturates, cannabinoids, amphetamines)

Urinary cortisol

Change in cortisol levels in picogram per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm

Urinary melatonin

Change in melatonin levels in picograms per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm

Clinical Global Impression (CGI)

CGI subscale scores for improvement and severity. Each subscale is scored on a 1-7 scale. Higher scores indicate worse (more severe) outcomes.

Short Form-36 v2 Health Survey

Overall health assessment. The 36 items are grouped into 8 dimensions: physical functioning, physical and emotional limitations, social functioning, bodily pain, general and mental health. Each scale is directly transformed into a 0-100 scale. Lower scores on each scale indicate greater disability.

Medication satisfaction

Assessment of satisfaction with assigned medication condition, on 1-7 Likert scale. Higher scores indicate greater medication satisfaction.

Full Information

NCT ID

NCT04262193

First Posted

February 6, 2020

Last Updated

July 12, 2023

Sponsor

Wayne State University

Collaborators

Henry Ford Health System

1. Study Identification

Unique Protocol Identification Number

NCT04262193

Brief Title

Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

Official Title

Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 1, 2021 (Actual)

Primary Completion Date

September 1, 2025 (Anticipated)

Study Completion Date

December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Wayne State University

Collaborators

Henry Ford Health System

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Summary of Study Protocol. This project is designed to test neurobehavioral mechanisms underlying effects of the dual orexin-1/2 receptor antagonist suvorexant on sleep efficiency and opioid abstinence, and whether these outcomes are independent of one another. This will be the first study to investigate whether suvorexant improves outpatient opioid abstinence and sleep efficiency; and whether improving sleep mediates the improved opioid abstinence outcome. 120 participants with opioid use disorder (OUD) who have just completed detoxification will complete this intent-to-treat study.

Detailed Description

Study Design. Using a placebo-controlled, parallel-group, randomized clinical trial design, we will prospectively evaluate whether nightly treatment with the orexin-1/2 receptor antagonist suvorexant (20 mg/day PO), relative to placebo, can increase outpatient opioid abstinence and improve sleep efficiency (sleep time per time-in-bed) as a mediator/moderator among patients with OUD. We have included current major depression and current alcohol use disorder severity as stratification factors in the group allocation. Using power and sample size calculations, we estimate that 60 participants in each study arm will suffice to test our hypotheses. The study aims to test three co-primary hypotheses: Hypothesis 1: Relative to placebo, suvorexant (20 mg/day) will significantly increase percentage opioid abstinence during outpatient weeks 1-13. Hypothesis 2: Relative to placebo, suvorexant will improve sleep efficiency. Hypothesis 3: Higher inpatient sleep efficiency will be associated with increased outpatient opioid abstinence (independent of experimental group assignment).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid-use Disorder, Sleep

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Participants will be randomly assigned to one of the 2 parallel groups for the duration of the study.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Suvorexant (20mg) and placebo research tablets will appear identical.

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Suvorexant placebo

Arm Type

Placebo Comparator

Arm Description

Placebo (inert) tablet

Arm Title

Suvorexant 20mg

Arm Type

Experimental

Arm Description

Suvorexant 20mg tablet

Intervention Type

Drug

Intervention Name(s)

Suvorexant

Other Intervention Name(s)

Belsomra

Intervention Description

In each group, the participant will take 1 tablet (placebo, 10mg or 20mg) 30 minutes before bedtime.

Intervention Type

Drug

Intervention Name(s)

Suvorexant Placebo

Intervention Description

Suvorexant Placebo

Primary Outcome Measure Information:

Title

Opioid abstinence

Description

Percentage of opioid-free urine drug screens (UDS)

Time Frame

up to 13 weeks

Title

Sleep efficiency

Description

Sleep efficiency equals sleep time (determined by standardized scoring of electroencephalogram recordings) divided by time in bed

Time Frame

Sleep efficiency is measured on the night before discharge from the inpatient unit

Secondary Outcome Measure Information:

Title

Daily sleep questionnaire

Description

Morning (post-awakening) assessment of sleep quality

Time Frame

Change in sleep quality scores from inpatient stay to outpatient weeks 2, 6 and 10

Title

Actigraphic assessment of sleep

Description

Actigraphic assessment of motion (activity counts), measured with Actiwatch and scoring software; motion is absent during sleep.

Time Frame

Change in total activity counts across outpatient weeks 2, 6 and 10

Title

Weekly sleep questionnaire

Description

Retrospective (past-week) self-report of sleep quality on each of 4 outpatient weeks

Time Frame

Change in sleep quality scores across outpatient weeks 1, 4, 8 and 12

Title

Timeline followback interview assessment of substance use

Description

Percentage of outpatient weeks with substance use (opioids, methadone, buprenorphine, cocaine metabolites, benzodiazepines, barbiturates, cannabinoids, amphetamines)

Time Frame

Once weekly (in conjunction with urine drug screen) on outpatient weeks 1 through 13

Title

Urinary cortisol

Description

Change in cortisol levels in picogram per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm

Time Frame

Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and melatonin assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit

Title

Urinary melatonin

Description

Change in melatonin levels in picograms per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm

Time Frame

Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and cortisol assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit

Title

Clinical Global Impression (CGI)

Description

CGI subscale scores for improvement and severity. Each subscale is scored on a 1-7 scale. Higher scores indicate worse (more severe) outcomes.

Time Frame

Change in CGI subscale scores across outpatient weeks 4, 8, and 12

Title

Short Form-36 v2 Health Survey

Description

Time Frame

Change in overall health total score across outpatient weeks 4, 8, and 12

Title

Medication satisfaction

Description

Assessment of satisfaction with assigned medication condition, on 1-7 Likert scale. Higher scores indicate greater medication satisfaction.

Time Frame

Change in medication satisfaction score across outpatient weeks 4, 8, and 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-70 years old Males and non-pregnant females who agree to medically accepted birth control for the duration of the study Meet DSM-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications [see below]) Must complete opioid detoxification (days 1-4 on the inpatient unit) Exclusion Criteria: Body mass index >38 Acute/unstable illness: conditions making it unsafe for participation, conditions with potential to disturb sleep (i.e. acute pain, respiratory infection) Chronic illnesses; renal failure, liver disease, seizures, and dementing illnesses Current psychiatric disease: psychosis, bipolar disorder, PTSD Smoking during the night (11pm-7am). Nicotine replacement therapy is allowed Medications including anxiolytics, hypnotics (both prescription and OTC), sedating antidepressants, anticonvulsants, sedating H1 antihistamines (non-sedating second generation H4 antihistamines are allowed), systemic steroids, respiratory stimulants and decongestants, prescription and OTC stimulants, prescription and OTC diet aids, herbal preparations, and narcotic analgesics. All medications and doses will be documented Sleep-disordered breathing and periodic leg movements (PLMs) defined as ≥ 10 apnea-hypopneas or PLM events related to EEG arousal per hour of sleep time, or any other primary sleep (e.g. narcolepsy, restless legs syndrome) or circadian disorder Night-shift work, which would alter circadian rhythm and be a confound in this trial.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mark K Greenwald, PhD

Phone

313-993-3965

mgreen@med.wayne.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark K Greenwald, PhD

Organizational Affiliation

Wayne State University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wayne State University

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48202

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mark Greenwald, PhD

Phone

313-993-3965

mgreen@med.wayne.edu

First Name & Middle Initial & Last Name & Degree

Mark Greenwald, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

This is under development, in collaboration with NIH officials. This project is funded under the NIH HEAL Initiative, which will require data sharing; details are being determined.

IPD Sharing Time Frame

Electronic copies of publications will be deposited within 4 weeks of acceptance. Underlying primary data will be made publicly available as soon as possible (time frame to be determined).

IPD Sharing Access Criteria

NIH will be managing sharing of data on a common web site (to be determined).

Learn more about this trial

Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

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