Cortisol; Hypersecretion, Craving, Sleep Disturbance
Conditions
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.
Interventions
DRUGSuvorexant 20 mg
Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia.
Sponsors
Milton S. Hershey Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
21 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Saliva samples were collected at five time points each day for four days, two days at baseline (Days 1 and 2) and two days at study end (Days 7 and 8). Baseline cortisol calculated as average of Days 1 and 2; endpoint cortisol calculated as average of Days 7 and 8. |
| 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 | The data were 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. Change in Modified Desire for Drug Scale measured on a 100-point Likert scale (0 = no craving, 100 = maximal craving). A negative change score indicates a decrease in craving across study time. |
| Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | 7 days | Endorsement of scale items associated with abuse liability 30 minutes after drug administration or the following morning. Change in Modified Abuse Liability Item Scores (0 = no change in abuse liability, 4 = maximal change in abuse liability). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Suvorexant 20 mg: Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia. | 6 |
| 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.
Suvorexant 20 mg: Suvorexant 20 mg is an orexin 1/2receptor antagonist approved for the treatment of sleep disturbance in subjects with Primary Insomnia. | 22 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 8 |
Baseline characteristics
| Characteristic | Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | Total | Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder |
|---|---|---|---|
| Age, Continuous | 40.91 years STANDARD_DEVIATION 12.49 | 39.64 years STANDARD_DEVIATION 12.24 | 35.00 years STANDARD_DEVIATION 10.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 28 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 28 Participants | 6 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 20 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 22 |
| other Total, other adverse events | 3 / 6 | 5 / 22 |
| serious Total, serious adverse events | 0 / 6 | 1 / 22 |
Outcome results
Primary
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.
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | 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. | -43.25 minutes | Standard Deviation 61.96 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | 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. | 12.68 minutes | Standard Deviation 41.42 |
Secondary
Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline.
Endorsement of scale items associated with abuse liability 30 minutes after drug administration or the following morning. Change in Modified Abuse Liability Item Scores (0 = no change in abuse liability, 4 = maximal change in abuse liability).
Time frame: 7 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Modified Liability Score (0-4 scale) | 0.29 score on a scale | Standard Deviation 0.36 |
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Abuse Liability Question (use drug to get high) | 0 score on a scale | Standard Deviation 0 |
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Abuse Liability Question (buy drug illegally) | 0 score on a scale | Standard Deviation 0 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Modified Liability Score (0-4 scale) | 0.10 score on a scale | Standard Deviation 0.17 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Abuse Liability Question (use drug to get high) | 0 score on a scale | Standard Deviation 0 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | Change in Scale Items on a Modified Abuse Liability Assessment Battery Relative to Baseline. | Abuse Liability Question (buy drug illegally) | 0 score on a scale | Standard Deviation 0 |
Secondary
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.
The data were 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. Change in Modified Desire for Drug Scale measured on a 100-point Likert scale (0 = no craving, 100 = maximal craving). A negative change score indicates a decrease in craving across study time.
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | 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. | -14.47 score on a scale | Standard Deviation 18.43 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | 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. | -8.70 score on a scale | Standard Deviation 13.18 |
Secondary
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.
Saliva samples were collected at five time points each day for four days, two days at baseline (Days 1 and 2) and two days at study end (Days 7 and 8). Baseline cortisol calculated as average of Days 1 and 2; endpoint cortisol calculated as average of Days 7 and 8.
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Trial of Suvorexant in Individuals With Opioid Use Disorder | 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. | 1.85 ng/ml | Standard Deviation 9.82 |
| Open Label Trial of Suvorexant in Individuals With Alcohol Use Disorder | 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. | -0.58 ng/ml | Standard Deviation 6.55 |