Orexin Antagonism for Suicide Risk: a Proof-of-Concept Clinical Trial

Phase 2

Not yet recruiting

• Conditions: Suicide Risk; Major Depressive Disorder (MDD)
• Interventions: Drug: Suvorexant (dual orexin receptor antagonist)

• Registration Number: NCT06854224
• Lead Sponsor: Marianne Goodman

Brief Summary

The goal of this proof-of-concept clinical trial is to evaluate the initial safety, feasibility, and tolerability of the orexin mixed antagonist suvorexant in a sample of veteran adults with Major Depressive Disorder and elevated suicide risk. The main question it aims to answer is: Is Suvorexant safe, feasible, and tolerable for participants?

Participants will:

* Take Surovexant every day for four weeks (10mg in the first two weeks and 20mg in the second two weeks)

* Visit the medical center at the beginning of the study (week 1), after taking Suvorexant for two weeks (week 3) and following the full Suvorexant dose (week 5) for in-person assessments.

* Fill out self-report assessments (remotely) at week 2 (after one week of Suvorexant) and week 4 (after three weeks of Surovexant)

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-02-25
• Study First Submitted QC: 2025-02-25
• Last Update Submitted: 2025-02-25
• Study First Posted: 2025-03-03
• Last Update Posted: 2025-03-03
• Study Start: 2025-04-01
• Primary Completion: 2027-07-01
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Veteran
• At least 18 years of age (up to 70 years)
• Primary diagnosis of Major Depressive Disorder as determined by the study psychiatrist and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
• Lifetime suicide attempt history and suicidal ideation at baseline as determined by a score ≥2 on the Columbia-Suicide Severity Rating Scale (C-SSRS)

Exclusion Criteria

• Clinically significant medical or neurological condition
• Current use of strong CYP3A live enzymes or moderate CYP3A inhibitors or strong CYP3A inducers
• Current use of digoxin
• Currently pregnant, not using contraception, nursing, or trying to become pregnant
• Active substance use disorder in the last six months, disorder, or current or past psychotic disorder, bipolar disorder, or obsessive-compulsive disorder
• Severe traumatic brain injury
• Imminent suicidal or homicidal risk
• Free of unstable medical conditions or any contraindication to suvorexant (per FDA prescribing label) as determined by patient interview and review of available medical records.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Suvorexant group	Suvorexant (dual orexin receptor antagonist)	Veteran patients with Major Depressive Disorder and elevated risk of suicide will receive the FDA-approved drug Suvorexant (brand name: Belsomra), a mixed Orexin antagonist, for four weeks. Participants will take 10mg of Surovexant nightly for the first two weeks and 20mg of Surovexant nightly for the second two weeks.

Primary Outcome Measures

Name	Time	Method
Suicide-related Implicit Association Test	Weeks 1, 3, and 5	Implicit Association Tests ( IATs) use reaction time (RT) to capture automatic, implicit processes to gauge implicit self-identification with a construct of interest. Participants classify stimuli presented in the center of the screen into categories. The category labels are located on the left and right of the screen and participants classify stimuli by selecting keys corresponding to the left or right. RTs are measured as participants complete this task thereby gauging implicit mental associations. This study uses a suicide-related IAT to determine the extent to which participants associated suicide-related constructs with the self.

Secondary Outcome Measures

Name	Time	Method
Buss-Perry Aggression Questionnaire	Weeks 1, 2, 3, 4, and 5	The Buss-Perry Aggression Questionnaire is a 20-item self-report questionnaire assessing four dimensions of aggression: physical aggression, verbal aggression, anger, and hostility. Participants indicate how well each item describes them on a 5-point scale ranging from 1 (Not at all like me) to 5 (Very much like me).
Point Subtraction Aggression Paradigm	Weeks 1, 3, and 5	The Point Subtraction Aggression Paradigm (PSAP) is a laboratory-based assessment of reactive aggression in which participants play a competitive computer game against a fictional opponent to obtain points that coincide with a monetary reward. The PSAP can be administered virtually through Inquisit Web, a software designed to facilitate virtual research experiments.
Overt Aggression Scale Modified	Weeks 1, 2, 3, 4, and 5	The Overt Aggression Scale Modified (OAS-M) is a clinician-administered interview of aggressive behavior. Participants are asked about "outbursts of anger" (reactive aggression) in the past week. The OAS-M is strongly related to measures of anger and differentiates between participants with and without intermittent explosive disorder, supporting its validity as a measure of reactive aggression.
Barratt Impulsiveness Scale	Weeks 1, 2, 3, 4, and 5	The Barratt Impulsiveness Scale (BIS-11) is a 30-item self-report questionnaire assessing the personality/behavioral construct of impulsiveness. It includes six first-order factors (attention, motor, self-control, cognitive complexity, perseverance, and cognitive instability impulsiveness) and three second-order factors (attentional, motor, and non-planning impulsiveness). Participants rate each item on a 4-point scale ranging from 1 (Rarely/Never) to 4 (Almost Always/Always). Total scores can range from 30 to 120.
Go/No-go task	Weeks 1, 3, and 5	The Go/No-go task is an experimental paradigm measuring impulsiveness. Cues consist of Go (green circle) and No-Go (red square) stimuli; participants are instructed to press the button as quickly as possible to Go stimuli, but withhold pressing to No-Go stimuli. Behavioral results scored include the total number of commission errors ("Go" responses on No-go trials), total number of omission errors ("No-Go" responses on Go trials), and reaction time on "Go" responses to (correct) Go and (incorrect) No-Go trials.
Beck Scale for Suicidal Ideation	Weeks 1, 2, 3, 4, and 5	The Beck Scale for Suicidal Ideation (BSSI) is a 21-item self-report questionnaire assessing suicidal thinking that helps identify individuals at risk. It also measures a broad spectrum of suicide-related attitudes and behaviors. The first five items are often used as the screener, where participants are directed to item 20 if they score 0 on these items. The overall score is computed by totaling up the scores on the first 19 items. Each item is rated from 0 to 2. Scores range from 0 to 38, with a higher score indicating a higher level of suicide ideation.
Columbia Suicide Severity Rating Scale	Weeks 1, 2, 3, 4, and 5	The Columbia Suicide Severity Rating Scale (C-SSRS) is a clinician-administered questionnaire assessing suicidal ideation and behavior with four subscales: ideation severity (five types of ideation of increasing severity), intensity of ideation (Frequency, Duration, Controllability, Deterrents, and Reasons for Ideation), suicidal behavior (4 types of suicidal behaviors - actual, interrupted, aborted attempts and preparatory behaviors - and the total number), and behavior lethality (For suicide attempts or non-suicidal self-injurious behavior).

Trial Locations

Locations (1)

James J. Peters Veterans Affairs Medical Center; 🇺🇸 Bronx, New York, United States