Opioid Dependence, Opioid Withdrawal, Sleep Disturbance
Conditions
Brief summary
This study will evaluate whether a dual orexin-receptor antagonist approved by the FDA for sleep disturbance, suvorexant (SUVO; Belsomra), will increase total sleep time in patients with opioid use disorder (OUD) undergoing supervised withdrawal. This study is designed as a dose-finding study of SUVO compared to placebo. Briefly, OUD patients seeking supervised withdrawal will be admitted into a clinical research unit and stabilized onto buprenorphine for three days before being randomly assigned to study condition. All participants will then undergo a routine four-day buprenorphine taper, followed by a four-day post-taper phase. Participants will be randomized to receive either placebo, Low Dose SUVO, or High Dose SUVO and the investigators hypothesize that one or both doses of SUVO will improve total sleep time relative to placebo. Patients will attend a single follow-up session, 5-10 days following discharge.
Interventions
DRUGPlacebo oral capsule
Placebo Sleep Medication
DRUGLow Dose Suvorexant
Low Dose Suvorexant
DRUGHigh Dose Suvorexant
High Dose Suvorexant
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged 18 years old and above * Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for OUD with evidence of physical dependence on opioids, and seeking treatment to stop using illicit opioids. * Provides a urine sample that tests positive for opioids. * Willing to comply with the study protocol. * Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation.
Exclusion criteria
* Seeking or currently enrolled in methadone or buprenorphine maintenance treatment for OUD * Pregnant or breast feeding * Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification * Have a known allergy to the study medications * Past 30-day prescribed use of suvorexant or benzodiazepines for the indication of insomnia * Current use of a Selective Serotonin Reuptake Inhibitor (SSRI) or Monoamine oxidase (MAO) inhibitor for depression or insomnia, or other medications that are contraindicated with suvorexant * Current narcolepsy, restless leg syndrome or sleep paralysis * High risk for current sleep apnea * Current major depressive disorder * Past year suicidal behavior * Severe hepatic or renal impairment * Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) \>3x ULN * Total bilirubin \>2x Upper Limit of Normal (ULN) * Creatinine \>1.5x ULN * Have circumstances that would interfere with study participation (e.g., impending jail)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abuse Liability as Assessed by Visual Analogue Scale | 4 nights | Area-under-the-curve of self-reported feelings of drug High on the morning after study drug administration, measured each morning on a 0-100 point visual analogue scale of the question Last night, did you feel HIGH?. A score of 0 indicates no abuse liability and a score of 100 indicates extreme abuse liability. This will be assessed over four nights during an opioid taper. |
| Total Sleep Time During Buprenorphine Taper | Four nights during a buprenorphine taper | Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy. |
| Total Sleep Time During Post-taper | Four nights following buprenorphine discontinuation | Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy. |
| Subjective Opiate Withdrawal Scale During Buprenorphine Taper | Three days during a buprenorphine taper | Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal). |
| Subjective Opiate Withdrawal Scale During Post-taper | Three days following buprenorphine discontinuation | Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal). |
Countries
United States
Participant flow
Pre-assignment details
90 individuals were consented and screened (35 did not meet eligibility criteria), 55 were scheduled for admission (7 did not present for admission), 48 were admitted for buprenorphine induction (2 were found to be ineligible at this stage and another 6 left prior to randomization), 40 were randomized (1 left before receiving study drug and 1 was excluded because of uncontrolled precipitated withdrawal), and 38 were included in the analyses of study outcomes.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo sleep medication (Placebo oral capsule)
Placebo oral capsule: Placebo Sleep Medication | 12 |
| Low Dose Suvorexant Low dose sleep medication
Low Dose Suvorexant: Low Dose Suvorexant | 14 |
| High Dose Suvorexant High dose sleep medication
High Dose Suvorexant: High Dose Suvorexant | 12 |
| Total | 38 |
Baseline characteristics
| Characteristic | Placebo | Low Dose Suvorexant | High Dose Suvorexant | Total |
|---|---|---|---|---|
| Age, Continuous | 41.0 years STANDARD_DEVIATION 10.4 | 36.7 years STANDARD_DEVIATION 9.4 | 46.3 years STANDARD_DEVIATION 12.7 | 41.1 years STANDARD_DEVIATION 11.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 8 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 10 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 10 Participants | 13 Participants | 10 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 14 | 0 / 12 | 0 / 38 |
| other Total, other adverse events | 6 / 12 | 8 / 14 | 7 / 12 | 10 / 38 |
| serious Total, serious adverse events | 0 / 12 | 0 / 14 | 0 / 12 | 0 / 38 |
Outcome results
Primary
Abuse Liability as Assessed by Visual Analogue Scale
Area-under-the-curve of self-reported feelings of drug High on the morning after study drug administration, measured each morning on a 0-100 point visual analogue scale of the question Last night, did you feel HIGH?. A score of 0 indicates no abuse liability and a score of 100 indicates extreme abuse liability. This will be assessed over four nights during an opioid taper.
Time frame: 4 nights
Population: Participants who completed the buprenorphine taper. 1 participant dropped out of the high dose suvorexant condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Abuse Liability as Assessed by Visual Analogue Scale | 23.9 score on a scale*days | Standard Deviation 33.5 |
| Low Dose Suvorexant | Abuse Liability as Assessed by Visual Analogue Scale | 20.9 score on a scale*days | Standard Deviation 28.7 |
| High Dose Suvorexant | Abuse Liability as Assessed by Visual Analogue Scale | 22.8 score on a scale*days | Standard Deviation 31 |
p-value: 0.95ANOVA
Primary
Subjective Opiate Withdrawal Scale During Buprenorphine Taper
Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal).
Time frame: Three days during a buprenorphine taper
Population: Participants who completed the buprenorphine taper. 1 participant dropped out of the high dose suvorexant condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Subjective Opiate Withdrawal Scale During Buprenorphine Taper | 15.5 score on a scale*days | Standard Deviation 12 |
| Low Dose Suvorexant | Subjective Opiate Withdrawal Scale During Buprenorphine Taper | 10.8 score on a scale*days | Standard Deviation 15.1 |
| High Dose Suvorexant | Subjective Opiate Withdrawal Scale During Buprenorphine Taper | 14.8 score on a scale*days | Standard Deviation 11.2 |
p-value: 0.62ANOVA
Primary
Subjective Opiate Withdrawal Scale During Post-taper
Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal).
Time frame: Three days following buprenorphine discontinuation
Population: Prior to completion of the post-taper phase, 4 participants dropped out from the placebo condition, 5 dropped out from the low-dose suvorexant condition, and 3 dropped out from the high-dose suvorexant condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Subjective Opiate Withdrawal Scale During Post-taper | 17.9 score on a scale*days | Standard Deviation 15.1 |
| Low Dose Suvorexant | Subjective Opiate Withdrawal Scale During Post-taper | 9.0 score on a scale*days | Standard Deviation 9.8 |
| High Dose Suvorexant | Subjective Opiate Withdrawal Scale During Post-taper | 6.4 score on a scale*days | Standard Deviation 3.9 |
p-value: 0.067ANOVA
Primary
Total Sleep Time During Buprenorphine Taper
Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy.
Time frame: Four nights during a buprenorphine taper
Population: Participants who completed the buprenorphine taper. 1 participant dropped out of the high dose suvorexant condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Sleep Time During Buprenorphine Taper | 891.6 minutes*nights | Standard Deviation 287.9 |
| Low Dose Suvorexant | Total Sleep Time During Buprenorphine Taper | 1183.6 minutes*nights | Standard Deviation 300.1 |
| High Dose Suvorexant | Total Sleep Time During Buprenorphine Taper | 1098.4 minutes*nights | Standard Deviation 287.3 |
p-value: 0.048ANOVA
Primary
Total Sleep Time During Post-taper
Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy.
Time frame: Four nights following buprenorphine discontinuation
Population: Prior to completion of the post-taper phase, 4 participants dropped out from the placebo condition, 5 dropped out from the low-dose suvorexant condition, and 3 dropped out from the high-dose suvorexant condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Sleep Time During Post-taper | 1049.3 minutes*nights | Standard Deviation 253.6 |
| Low Dose Suvorexant | Total Sleep Time During Post-taper | 1113.2 minutes*nights | Standard Deviation 342.1 |
| High Dose Suvorexant | Total Sleep Time During Post-taper | 1055.9 minutes*nights | Standard Deviation 274.5 |
p-value: 0.691ANOVA