Alcohol Use DisorderEarly Phase 1NCT05656534
Orexin Receptor Antagonists as Modulators of Threat Sensitivity in Individuals With Alcohol Use Disorder
A Early Phase 1 study testing Suvorexant in people with Alcohol Use Disorder, run by Ohio State University at 1 site in United States.
Trial summary
The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Suvorexant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Nov 2022to 1 Aug 2024
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-65.
- Participant is able to give informed consent.
- Generally medically and physically healthy as confirmed by medical history.
- Meet DSM-5 diagnostic criteria for current moderate or severe AUD.
- Engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female.
Who cannot join
- Clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, COPD, severe obstructive sleep apnea).
- Current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia).
- Current use of antihistamines, strong or moderate inhibitors of CYP3A liver enzymes, strong CYP3A inducers, or digoxin.
- Current or past DSM-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder.
- Current substance use disorder other than alcohol or mild cannabis use disorder.
- Treatment seeking for AUD.
Show all 15Show fewer
- Recent psychotropic medication use in the past 2 months.
- Currently smokes 5 or more cigarettes (or electronic equivalent) per day.
- BMI equal or greater than 35.
- Engage in night-shift work.
- Lack of fluency in English.
- Presence of ferrous-containing metal in the body.
- Inability to tolerate small, enclosed spaces.
- Deafness in one or both ears.
- Currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are:
- Does an acute dose of suvorexant (SUV) and/or daily use of SUV modify brain-behavior targets of AUD dysfunction?
- Does daily SUV use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change?
Read more
Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following:
- Baseline lab visit(s) that include the psychophysiological stress paradigm (EMG only or EMG+fMRI, dependent upon randomization).
- Acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg SUV or placebo.
- Medication trial where participants will be instructed to take 10mg capsules of SUV or placebo orally each night before bedtime for 4-weeks.
- Daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial.
- Post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (EMG only or EMG+fMRI, dependent upon randomization).
- Conditions
- Alcohol Use Disorder
- Being tested
- Suvorexant, Placebo
- Keywords
- suvorexant, alcohol use disorder, electromyography, functional magnetic resonance imaging
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SuvorexantDrug
Also called Belsomra
This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits.
PlaceboOther
This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. Receives: Other: Placebo |
| Suvorexant Treatment | Experimental | Individuals will take 10mg of suvorexant (Merck \& Co Inc.) during the Acute Drug Challenge and daily for 28 days. Receives: Drug: Suvorexant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. U-threat residual scores were calculated for the baseline session and the acute challenge.
Measured: Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant.
Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant.
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat.
Measured: Change from baseline to post-treatment, up to 2 months.
Percentage of Heavy Drinking Days During Daily Use of Suvorexant.
Percentage of heavy drinking days (PHDD) was calculated each week for all four weeks of the trial. A heavy drinking day was defined using NIH criteria: 5+ drinks for males and 4+ drinks for females in a single day. We conducted a multilevel mixed model with PHDD from week 1 to 4 as the within-subjects variable and treatment arm as the between subjects variable.
Measured: Change from baseline to post-treatment, over the course of 4 weeks.
Secondary outcomes (1)
Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant.
Activation parameter estimates (arbitrary units) were extracted from anatomical bilateral aINS masks for each individual, pre and post treatment. Specifically, activation parameter estimates were extracted from anticipation of unpredictable threat > anticipation of no-threat individual contrast maps for each scanning session. Greater values reflect greater activation in the bilateral insula during the anticipation of unpredictable threat. A repeated measures analysis of variance was used to test the session (time 1 vs. time 2) by treatment arm interaction on bilateral aINS activation during unpredictable threat. Significance was set at p <.05
Measured: Change from baseline to post-treatment, up to 2 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2022
- Study start29 Nov 2022
- Primary completion1 Aug 2024
- Study completion1 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Stephanie M Gorka, PhD, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05656534
- Sponsor's protocol ID
- 2022H0265
- Other IDs
- 1R21AA030097-01A1
- Status last verified
- Oct 2025
- First submitted
- 11 Dec 2022
- Last updated
- 30 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data, including fMRI, startle eyeblink, and behavior, from this project will be submitted to the NIAAA Data Archive (NDA) at the subject level along with appropriate supporting documentation to enable efficient use of the data by the research community. We will follow instructions as discussed in the NIAAA Data Archive Data Sharing Terms and Conditions. We will follow the two-tier procedure described in the guidelines: 1. Raw continuous fMRI recordings will be submitted in standard formats (Matlab mat format, DICOM format and NIFTI format). Experimental condition information will be supplied in text format along with other critical information. 2. Analyzed data (BOLD data, BOLD-startle eyeblink data) associated with a manuscript will be shared as soon as possible, and at the latest, at the time of publication of the manuscript. These data may be accompanied, if applicable, by other data such as behavioral data, supplied in text format.
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Orexin Receptor Antagonists as Modulators of Threat Sensitivity in Individuals With Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT05656534
- Acronym / sponsor ID
- 2022H0265
- Conditions
- Alcohol Use Disorder
- Keywords
- suvorexant, alcohol use disorder, electromyography, functional magnetic resonance imaging
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 29 Nov 2022 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 1 Aug 2024 (actual)
- First posted
- 19 Dec 2022 (actual)
- Results
- Posted 30 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are:
- Does an acute dose of suvorexant (SUV) and/or daily use of SUV modify brain-behavior targets of AUD dysfunction?
- Does daily SUV use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change?
Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following:
- Baseline lab visit(s) that include the psychophysiological stress paradigm (EMG only or EMG+fMRI, dependent upon randomization).
- Acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg SUV or placebo.
- Medication trial where participants will be instructed to take 10mg capsules of SUV or placebo orally each night before bedtime for 4-weeks.
- Daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial.
- Post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (EMG only or EMG+fMRI, dependent upon randomization).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Other: PlaceboIndividuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days. |
| Suvorexant Treatment | Experimental | Drug: SuvorexantIndividuals will take 10mg of suvorexant (Merck \& Co Inc.) during the Acute Drug Challenge and daily for 28 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18-65.
- Participant is able to give informed consent.
- Generally medically and physically healthy as confirmed by medical history.
- Meet DSM-5 diagnostic criteria for current moderate or severe AUD.
- Engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female.
Key exclusion criteria (15 listed)
- Clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, COPD, severe obstructive sleep apnea).
- Current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia).
- Current use of antihistamines, strong or moderate inhibitors of CYP3A liver enzymes, strong CYP3A inducers, or digoxin.
- Current or past DSM-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder.
- Current substance use disorder other than alcohol or mild cannabis use disorder.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SuvorexantAlso: BelsomraThis study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits. | Drug | Suvorexant Treatment |
| PlaceboThis study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits. | Other | Control |
Primary outcome
Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant
Time frame: Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant.
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat. U-threat residual scores were calculated for the baseline session and the acute challenge.
Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant.
Time frame: Change from baseline to post-treatment, up to 2 months.
Startle EMG responses were collected during the well-validated No-Predictable-Unpredictable threat paradigm. The task includes within-subjects conditions and raw EMG responses were averaged for each condition. To quantify the difference between threat and no-threat periods, we calculated a standardized residual score for unpredictable threat (U-threat) by saving the variance leftover (i.e., the amount of variability in a dependent variable [DV] that is not explained by an independent variable [IV]) in a simple linear regression, where the no-threat EMG startle average (IV) was entered to predict the U-threat EMG startle average (DV). The U-threat residual score was used as the primary variable. It has a mean of zero and higher scores reflect greater startle reactivity to U-threat.
Percentage of Heavy Drinking Days During Daily Use of Suvorexant.
Time frame: Change from baseline to post-treatment, over the course of 4 weeks.
Percentage of heavy drinking days (PHDD) was calculated each week for all four weeks of the trial. A heavy drinking day was defined using NIH criteria: 5+ drinks for males and 4+ drinks for females in a single day. We conducted a multilevel mixed model with PHDD from week 1 to 4 as the within-subjects variable and treatment arm as the between subjects variable.
1 secondary outcome
Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant.
Time frame: Change from baseline to post-treatment, up to 2 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. De-identified data, including fMRI, startle eyeblink, and behavior, from this project will be submitted to the NIAAA Data Archive (NDA) at the subject level along with appropriate supporting documentation to enable efficient use of the data by the research community. We will follow instructions as discussed in the NIAAA Data Archive Data Sharing Terms and Conditions. We will follow the two-tier procedure described in the guidelines: 1. Raw continuous fMRI recordings will be submitted in standard formats (Matlab mat format, DICOM format and NIFTI format). Experimental condition information will be supplied in text format along with other critical information. 2. Analyzed data (BOLD data, BOLD-startle eyeblink data) associated with a manuscript will be shared as soon as possible, and at the latest, at the time of publication of the manuscript. These data may be accompanied, if applicable, by other data such as behavioral data, supplied in text format.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Suvorexant in people with Alcohol Use Disorder, run by Ohio State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant (time frame: Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025.