Clinical trial NCT03412591: The Efficacy of Suvorexant in Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial
Official title: The Efficacy of Suvorexant in the Residential Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sleep Disturbance
Craving
Cortisol; Hypersecretion
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2018-01-26
Enrollment: 28
Sex: ALL
Minimum age (years): 21
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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 purpose: TREATMENT

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. 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 7 days
Secondary outcomes:
measure: 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.
timeFrame: 7 days
measure: 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.
timeFrame: 7 days
measure: Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline.
timeFrame: 7 days
Other outcomes:
Locations:
city: Wernersville
country: United States
facility: Richard J Caron Foundation
state: Pennsylvania
Study officials:
affiliation: Penn State University Hershey Medical Center
name: Venkatesh Basappa Krishnamurthy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
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