Daridorexant for Alcohol Use Disorder

A Double-Blind Randomized Controlled Trial of Daridorexant for Alcohol Use Disorder

This study will test whether the dual orexin receptor antagonist (DORA) daridorexant reduces alcohol craving and use and improves total sleep time among patients with co-occurring alcohol use disorder and sleep disturbance. The study will assess the role of the orexin system in modulating alcohol craving and use in a real-world treatment setting.

Study Overview

• Status: Not yet recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Daridorexant 50 mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jennifer Ellis; Phone Number: 410-550-6346; Email: jellis36@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current moderate or severe DSM-5 criteria for AUD at the time of the screening session
• Evidence of clinically significant sleep disturbance, based on the Pittsburgh Sleep Quality Index (PSQI; i.e., score >5)
• Aged 18 years or older
• Willingness to comply with all components of the study protocol
• Use of birth control throughout the study, if a pre-menopausal female who is not sterile, and who is sexually active with a male partner or considering being sexually active with a male partner
• Report ability to access a computer with an internet connection during the outpatient phase of the study to complete virtual outpatient visits
• Report a desire to quit or reduce drinking (i.e., not enrolling in treatment solely to satisfy an external requirement)
• Able to provide informed consent, and evidence an understanding of study procedures based on a quiz following informed consent
• Fluent in English (in order to complete study assessments).

Exclusion Criteria:

• Current moderate or severe substance use disorder other than AUD, cannabis use disorder, nicotine use disorder, or caffeine use disorder
• Pregnant or breastfeeding, or planning to become pregnant during the study
• Known allergy to any DORA
• Past 30-day use of any DORA
• Current use of benzodiazepines or other schedule IV medications for insomnia
• Use of any medications that are contraindicated for use with daridorexant
• Current withdrawal symptoms, as assessed by a score >8 on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and benzodiazepine administration in the past 24 hours
• Past-year suicidal behavior
• Current bipolar disorder or psychotic disorder
• Abnormal liver enzyme levels (i.e., AST or ALT greater than five times above the upper limit of normal, or bilirubin greater than two times the upper limit of normal), as assessed during standard intake procedures at Ashley Addiction Treatment
• AHI>30, as assessed using a wireless EEG/apnea device, to rule out those with severe sleep apnea
• Any other medical or psychological condition that is judged by the investigators to impede ability to safely complete study requirements
• Legal problems or living situation judged by the investigators as a factor that could interfere with study completion (e.g., impending jail time).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daridorexant; Daridorexant 50mg (Oral)	Drug: Daridorexant 50 mg; Daridorexant 50 mg (Orally administered)
Placebo Comparator: Placebo; Placebo (Oral)	Other: Placebo; Placebo (Oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Sleep Time (Minutes)	Total sleep time will be assessed through both wireless EEG and ambulatory monitoring. Wireless EEG will be assessed during the residential phase only. Ambulatory monitoring will occur during both the residential and outpatient phase.	Enrollment to one month follow-up
Alcohol Craving Visual Analogue Scale	Visual Analogue Scales assessing alcohol craving will be administered (Range 0-100, higher scores indicate greater craving).	Enrollment to one month follow-up
Daily alcohol use, assessed via Timeline Followback (TLFB)		Outpatient phase (Day 1 post-residential treatment to one-month follow-up)
Number of Adverse Events		From enrollment to one month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily binge drinking, assessed via Timeline Followback (TLFB)		Outpatient phase (Day 1 post-residential treatment to one-month follow-up)
Number of Participants with Positive breathalyzer screen		Outpatient phase (Day 1 post-residential treatment to one-month follow-up)
Number of Alcohol use disorder symptoms	Alcohol use disorder symptoms, assessed using the Alcohol Use Disorders module of the Mini-International Neuropsychiatric Interview. 9-items rated on a dichotomous Yes/No scale.	Enrollment to one-month follow-up
Self-Reported Insomnia Severity	Self-reported insomnia severity, assessed using the Insomnia Severity Index. Each item is scored 0 (no problem) - 4 (very big problem) likert scale with total score range between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).	Enrollment to one-month follow-up

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institutes of Health (NIH); Idorsia Pharmaceuticals Ltd.
• Investigators: Principal Investigator: Jennifer Ellis, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 8, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; daridorexant
• Other Study ID Numbers: IRB00492313

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be shared via the NIAAA Data Archive following publication. Access will be controlled and require submission of a Data Access Request. Supporting documentation will also be provided.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No