The Efficacy of Suvorexant in Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial

NCT03412591 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00005409
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Insomnia is an extremely common and poorly treated problem in patients with substance use disorders (SUD)s undergoing rehabilitation treatment in a residential facility. The persistence of insomnia in substance use disorders (SUDs) may be associated with tonic levels of drug craving. Insomnia and craving can predispose to relapse in patients with SUDs. Insomnia and SUDs are independently associated with increased cortisol indicating physiological dysregulation of the stress response system including the hypothalamic-pituitary-adrenal (HPA) axis. Hence sleep disturbance, craving and increased cortisol leads to relapse in SUD subjects. Suvorexant, an orexin 1 / 2 receptor antagonist, approved by the FDA for the treatment of sleep disturbance in subjects with primary Insomnia. Previous animal studies report Orexin 1 receptor antagonist decreases craving and normal the HPA axis. However, the efficacy of suvorexant on sleep and craving in SUD subjects is not known. The primary aims of this study are-

1. 1.To determine if suvorexant will improve sleep quality (increased total sleep time, fewer awakenings), as measured through wrist actigraphy and the Insomnia Severity Index (ISI) in SUDs.
2. 2.To assess whether or not SUDs patients treated with suvorexant endorse scale items on a modified abuse liability assessment battery.
3. 3.To determine if daily reports of mood, stress, craving and sleep using Ecological Momentary Assessment (EMA data) change during the course of the study as patients with SUDs are treated with suvorexant.
4. 4.To determine if patients taking suvorexant will have a decrease in total daily salivary cortisol over the course of the study by collecting samples at five time points in a day, for two consecutive days at two different times in the study.

Conditions

Sleep Disturbance; Craving; Cortisol; Hypersecretion

Outcome Measures

Primary Outcomes (1)

• Change in Total Sleep Time as Measured by Actigraphy and Sleep Logs Relative to Baseline Over the Course of 7 Days of Treatment With Suvorexant in Substance Use Disorder Patients.

  7 days

Secondary Outcomes (3)

• Relative to a Baseline, Change in Total Daily Salivary Cortisol Over the Course of 7 Days of Treatment With Suvorexant in Substance Use Disorder Patients.

  7 days

• Relative to a Baseline, Change in Daily Reports of Craving Using Ecological Momentary Assessment (EMA Data) Over the Course of 7 Days of Treatment With Suvorexant in Substance Use Disorder Patients.

  7 days

• Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline.

  7 days

Study Arms (2)

Open label trial of suvorexant in individuals with opioid use disorder

OTHER

It is an open label trial to study the efficacy of suvorexant in a group of patients with opioid use disorder.

Drug: Suvorexant 20 mg

Open label trial of suvorexant in individuals with alcohol use disorder

OTHER

It is an open label trial to study the efficacy of suvorexant in a group of patients with alcohol use disorder.

Drug: Suvorexant 20 mg

Interventions

Suvorexant 20 mg DRUG

Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia.

Also known as: Belsomra

Open label trial of suvorexant in individuals with alcohol use disorder; Open label trial of suvorexant in individuals with opioid use disorder

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Sex: male or female
• Age: 21-64 (inclusive) years old
• Caron Foundation residential alcohol or opioid dependent patients that have a history of daily or near daily substance use for the month prior to admittance.
• Group 1: at least five days post medically assisted withdrawal for alcohol dependence, and complain of problems falling asleep, remaining asleep after sleep onset, or poor sleep quality on current sleep medication (antidepressant/melatonin).
• Group 2: at least five days post medically assisted withdrawal for opioid dependence and complain of problems falling asleep, remaining asleep after sleep onset, or poor sleep quality on current sleep medication (antidepressant/melatonin).
• Fluent in written and spoken English.

You may not qualify if:

• Patients who are concurrently receiving a psychoactive drug for the treatment of an Axis I disorder excluding sedating antidepressants that have been prescribed for the treatment of sleep disturbance.
• Patients with current major depressive disorder, schizophrenia, bipolar disorder, post traumatic stress disorder, or a history of traumatic brain injury.
• Patients with a history of narcolepsy or REM related phenomenon.
• Patients with chronic respiratory problems including asthma, COPD, or other respiratory issues that can lead to sleep disturbances at night.
• Patients with current suicidal ideation, or a history of previous suicide attempts.
• Patients with severe liver impairment.
• Women who are pregnant or breastfeeding.
• Patients who are severely obese.
• Decisional impairment
• Prisoners or under legal mandate.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Richard J Caron Foundation

Wernersville, Pennsylvania, 19567, United States

Location

Related Publications (17)

• US Food and Drug Administration (2013). Suvorexant Advisory Committee Meeting briefing document.http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/peripheralandcentralnervoussystemdrugsadvisorycommittee/ucm352970.pdf. Accessed 9 Sep 2014

  BACKGROUND

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  PMID: 22356621 BACKGROUND

• Giardino WJ, de Lecea L. Hypocretin (orexin) neuromodulation of stress and reward pathways. Curr Opin Neurobiol. 2014 Dec;29:103-8. doi: 10.1016/j.conb.2014.07.006. Epub 2014 Jul 20.

  PMID: 25050887 BACKGROUND

• Koob G, Kreek MJ. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry. 2007 Aug;164(8):1149-59. doi: 10.1176/appi.ajp.2007.05030503.

  PMID: 17671276 BACKGROUND

• Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci. 2011 Oct 20;12(11):652-69. doi: 10.1038/nrn3119.

  PMID: 22011681 BACKGROUND

• Brower KJ. Alcohol's effects on sleep in alcoholics. Alcohol Res Health. 2001;25(2):110-25.

  PMID: 11584550 BACKGROUND

• Conroy DA, Arnedt JT. Sleep and substance use disorders: an update. Curr Psychiatry Rep. 2014 Oct;16(10):487. doi: 10.1007/s11920-014-0487-3.

  PMID: 25135784 BACKGROUND

• Hasler BP, Smith LJ, Cousins JC, Bootzin RR. Circadian rhythms, sleep, and substance abuse. Sleep Med Rev. 2012 Feb;16(1):67-81. doi: 10.1016/j.smrv.2011.03.004. Epub 2011 May 26.

  PMID: 21620743 BACKGROUND

• American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. (DSM V) 361-368.

  BACKGROUND

• Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57.

  PMID: 9881538 BACKGROUND

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  PMID: 14399272 BACKGROUND

• Miller WR (1996): Form 90: A structured assessment interview for drinking and related behaviors. Center for Alcoholism: Substance Abuse and Addiction, University of New Mexico, Albuquerque.

  BACKGROUND

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

  PMID: 2748771 BACKGROUND

• Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.

  PMID: 11438246 BACKGROUND

• Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.

  PMID: 3397865 BACKGROUND

• Tiffany ST, Wray JM. The clinical significance of drug craving. Ann N Y Acad Sci. 2012 Feb;1248:1-17. doi: 10.1111/j.1749-6632.2011.06298.x. Epub 2011 Dec 16.

  PMID: 22172057 BACKGROUND

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  PMID: 10445371 BACKGROUND

MeSH Terms

Conditions

Parasomnias

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Limitations and Caveats

1. Recruitment difficulties led to small numbers in the opioid use group. High number of withdrawals in the alcohol use group impacted the number of participants available for analysis. 2. For TST outcome, technical problems led to n=4 (instead of n=5) for analysis in the opioid use group. In the alcohol use group, n=13 completed the study. An additional participant completed all but one day of the study (withdrew Day 8); data was available for analysis. Total of n=14 for analysis.

Results Point of Contact

• Title: Dr. Scott Bunce
• Organization: Penn State College of Medicine

sbunce@pennstatehealth.psu.edu

2155108295

Study Officials

• Venkatesh Basappa Krishnamurthy, MD

  Penn State University Hershey Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: We intend to evaluate the efficacy of suvorexant in a group of opioid dependent (n=14) and a group of alcohol dependent subjects (n=14) in a residential treatment facility. It is an open label trial on subjects with opioid or alcohol dependence who are 5to 10 days post withdrawal.

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: January 26, 2018
• Study Start: July 1, 2019
• Primary Completion: January 7, 2023
• Study Completion: January 7, 2023
• Last Updated: February 13, 2024
• Results First Posted: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)