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

NCT ID: NCT03412591

Last Updated: 2024-02-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-01

Study Completion Date

2023-01-07

Brief Summary

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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. 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. To assess whether or not SUDs patients treated with suvorexant endorse scale items on a modified abuse liability assessment battery.
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. 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.

Detailed Description

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Insomnia is an extremely common and poorly treated problem in patients with substance use disorders (SUD)s patients undergoing rehabilitation treatment in 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 is a novel orexin 1 and 2 receptor antagonist, FDA approved for the treatment of insomnia. Suvorexant may be differentially beneficial in patients with opioid dependence: 1) It is efficacious for treatment of insomnia in the general population, 2) Data from animal models of opioid dependence suggest that orexins may be involved in reward (opioid) seeking behavior and altered stress response while an orexin antagonist appears to decrease reward (opioid) seeking while normalizing HPA axis function. A medication that can improve sleep, decrease craving and normalize the HPA axis may theoretically be helpful in patients with SUDs. At this juncture, the literature supports the case for an open trial of Suvorexant for patients in residential care for SUDs, who complain of sleep disturbance. The patients will be at least 5 days post-withdrawal, in order to minimize the residual sleep complaints associated with that phase of treatment.

In previous, well-designed, placebo-controlled clinical trials in patients with insomnia, suvorexant has been shown to be efficacious compared with placebo. However, substance dependent patients with insomnia were not included in these studies. Although, as a new sleep medication, suvorexant has been placed in Schedule IV by the FDA, the drug has not been studied in the context of its potential abuse liability when administered at bedtime at the therapeutic dose among patients in residential treatment for substance dependence disorders. A modified abuse liability protocol will therefore be incorporated in this pilot study.

The hypothesis for this study are-

1. Relative to a baseline, patients treated with suvorexant will experience an increase in total sleep time, fewer awakenings after sleep onset, and improved subjective sleep quality.
2. Patients treated with suvorexant are not likely to endorse scale items associated with abuse liability 30 minutes after drug administration or the following morning.
3. Relative to baseline, patients being treated with suvorexant are more likely to report improved moods, and decreased ambient craving.
4. Relative to baseline, patients being treated with suvorexant are more likely to experience decreased total daily salivary cortisol over the course of 7 days of treatment with suvorexant.

Conditions

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Sleep Disturbance Craving Cortisol; Hypersecretion

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Open label trial of suvorexant in individuals with opioid use disorder

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

Group Type OTHER

Suvorexant 20 mg

Intervention Type DRUG

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

Open label trial of suvorexant in individuals with alcohol use disorder

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

Group Type OTHER

Suvorexant 20 mg

Intervention Type DRUG

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

Interventions

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Suvorexant 20 mg

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

Intervention Type DRUG

Other Intervention Names

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Belsomra

Eligibility Criteria

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Inclusion Criteria

1. Sex: male or female
2. Age: 21-64 (inclusive) years old
3. 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).
4. Fluent in written and spoken English.

Exclusion Criteria

1. 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.
2. Patients with current major depressive disorder, schizophrenia, bipolar disorder, post traumatic stress disorder, or a history of traumatic brain injury.
3. Patients with a history of narcolepsy or REM related phenomenon.
4. Patients with chronic respiratory problems including asthma, COPD, or other respiratory issues that can lead to sleep disturbances at night.
5. Patients with current suicidal ideation, or a history of previous suicide attempts.
6. Patients with severe liver impairment.
7. Women who are pregnant or breastfeeding.
8. Patients who are severely obese.
9. Decisional impairment
10. Prisoners or under legal mandate.
Minimum Eligible Age

21 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Milton S. Hershey Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Scott C Bunce, PhD

Associate Professor of Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Venkatesh Basappa Krishnamurthy, MD

Role: PRINCIPAL_INVESTIGATOR

Penn State University Hershey Medical Center

Locations

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Richard J Caron Foundation

Wernersville, Pennsylvania, United States

Site Status

Countries

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United States

References

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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

Reference Type BACKGROUND

Smith RJ, Aston-Jones G. Orexin / hypocretin 1 receptor antagonist reduces heroin self-administration and cue-induced heroin seeking. Eur J Neurosci. 2012 Mar;35(5):798-804. doi: 10.1111/j.1460-9568.2012.08013.x. Epub 2012 Feb 22.

Reference Type BACKGROUND
PMID: 22356621 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25050887 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17671276 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22011681 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11584550 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25135784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21620743 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 9881538 (View on PubMed)

HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.

Reference Type BACKGROUND
PMID: 14399272 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 2748771 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11438246 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3397865 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22172057 (View on PubMed)

Rush CR, Frey JM, Griffiths RR. Zaleplon and triazolam in humans: acute behavioral effects and abuse potential. Psychopharmacology (Berl). 1999 Jul;145(1):39-51. doi: 10.1007/s002130051030.

Reference Type BACKGROUND
PMID: 10445371 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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STUDY00005409

Identifier Type: -

Identifier Source: org_study_id

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