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

Study Overview
=================
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- 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. To assess whether or not SUDs patients treated with suvorexant endorse scale items on a modified abuse liability assessment battery. 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. 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- 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. Patients treated with suvorexant are not likely to endorse scale items associated with abuse liability 30 minutes after drug administration or the following morning. Relative to baseline, patients being treated with suvorexant are more likely to report improved moods, and decreased ambient craving. 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.

Official Title
-----------------
The Efficacy of Suvorexant in the Residential Treatment of Patients With Substance Use Disorder and Insomnia: A Pilot Open Trial

Conditions
-----------------
Sleep Disturbance, Craving, Cortisol; Hypersecretion

Intervention / Treatment
-----------------
* Drug: Suvorexant 20 mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open label trial of suvorexant in SUDs<br>It is an open label trial to study the efficacy of suvorexant in a group of opioid use and alcohol use disorder subjects. | Drug: Suvorexant 20 mg<br>* Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia.<br>* Other names: Belsomra;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative to a baseline, change in total sleep time as measured by actigraphy and sleep logs over the course of 7 days of treatment with suvorexant in substance use disorder patients. | Relative to a baseline (on antidepressants or melatonin), patients being treated with suvorexant for 7 days will experience an increase in total sleep time. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | suvorexant will decrease total daily salivary cortisol over the course of the study. Saliva samples will be collected at five time points for two consecutive days at two different times in the study. | 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. | Relative to baseline, patients being treated with suvorexant are more likely to endorse decreased ambient craving. The data will be collected via Motorola Droid smart phones that are programmed to elicit the participants' response four times per day, during each of the 9 full study days. | 7 days | 
| Relative to a baseline, if patients treated with suvorexant endorse scale items on a modified abuse liability assessment battery. | Patients being treated with suvorexant are not likely to endorse scale items associated with abuse liability 30 minutes after drug administration or the following morning. | 7 days |