suvorexant for treatment of aud and ptsd

Conditions: Alcohol Use Disorder (AUD); Post Traumatic Stress Disorder (PTSD); Insomnia

Summary: this study is to determine if suvorexant (suv) will reduce insomnia in 76 men and women veteran and non-veterans between the ages 21-65 with posttraumatic stress disorder (ptsd) symptoms and alcohol use disorder (aud). all participants will have a 7-day placebo run-in period, followed by a random assignment to receive placebo or suvorexant for an additonal 14 days. post-randomization, participants will attempt to stop drinking for two weeks and will complete daily virtual diaries and study outcome assessments via in-person clinic visits on days 7 and 14.

this is a randomized, double-masked, placebo-controlled study to evaluate preliminary efficacy and safety of suvorexant (suv) (20mg) for sleep disturbance in alcohol use disorder (aud) and co-occurring posttraumatic stress disorder (ptsd) symptoms in approximately 76 randomized men and women veteran and non-veterans between the ages 21-65. participants will be recruited from the university of texas health science center at houston (uthealth) trauma and recovery center (trc) and the university of california - los angeles (ucla) (in collaboration with west los angeles va medical center). following a 7-day placebo run-in, participants will be randomly assigned to receive suv (10mg (days 0-6) and 20mg (days 7-13)) or matched placebo. randomization will be stratified on sex and level of sleep disturbance (insomnia severity index (isi) score). post-randomization, all participants will complete an alcohol cue-reactivity paradigm prior to the initial dose of study medication. the alcohol cue-reactivity paradigm is an established laboratory assessment of craving during which participants are exposed to real alcohol and water cues in a bar laboratory setting. participants will then take their first dose of medication. participants will begin the real-world quit attempt, during which they will attempt to stop drinking for two weeks. participants will complete daily virtual diaries and visits to assess sleep, past-day drinking, and alcohol craving. participants will return to one of the clinical sites on study day 14 to complete an alcohol cue-reactivity session to assess post-medication craving. ptsd symptoms will be assessed via clinician-administered ptsd scale for diagnostic and statistical manual of mental disorders, fifth edition (caps-5) and post-traumatic stress disorder checklist for diagnostic and statistical manual of mental disorders, fifth edition (pcl-5) at baseline, at day 7 and at day 14 of treatment with suv or matched placebo.

Eligibility criteria:
inclusion criteria: * age between 21 and 65. * meet current (i.e., past 12-month at day -7/-6) dsm-5 diagnostic criteria for moderate or severe aud as determined by the mini. * currently experiencing ptsd symptoms at screening (day -7/-6) as indicated by pcl-5 cut-score \> 30. * intrinsic motivation to reduce or quit drinking (defined as self-reported intention at screening to reduce or quit drinking within the next 6 months) and to receive ptsd treatment. * must have an isi score equal to or \> 7 (subthreshold insomnia). isi score below 7 at screening will not be included or proceed beyond the screening day. * agree to abstain from all other sleep medications (starting at day -7). * have a place to live in the 2 weeks prior to randomization (day 0) and not be at risk that s/he will lose his/her housing in the next month. exclusion criteria: * a current (past 12-month at day -7/-6) dsm-5 diagnosis via the mini of substance use disorder for any substances other than alcohol, nicotine, or marijuana (\< moderate level on dsm 5). * a lifetime dsm-5 diagnosis via the mini of schizophrenia, bipolar disorder, or psychotic disorder. * positive urine test for any recreational drugs other than marijuana at screening (day -7/-6). * current clinically significant alcohol withdrawal (i.e., score ≥ 10 on the ciwa-ar). * currently pregnant, nursing, or no reliable method of birth control (females only). * any clinically significant medical condition that would preclude safe participation in the study (e.g. narcolepsy, seizure disorder, or other clinically significant cardiovascular, hematologic, hepatic, renal, neurological, or endocrine disorders). * use of suvorexant (within 30 days of day -7). * currently on prescription medication that contraindicates use of suvorexant (including moderate or strong cytochrome p450 3a modulators (cyp3a inhibitors and inducers)) * hepatic insufficiency (ast/alt \> 5x upper limit of normal (uln)). * suicidal ideation determined by greater than moderate columbia suicide severity rating scale. * inability to provide evidence of 48-hour alcohol abstinence (self-report, brac, etg) at day 0 and failure after second attempt at 48-hour abstinence.