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

NCT06854224 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 1851192
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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)

Conditions

Suicide Risk; Major Depressive Disorder (MDD)

Keywords

Suicide risk; Proof-of-concept clinical trial; Suvorexant; Orexin antagonist

Outcome Measures

Primary Outcomes (1)

• Implicit Association Tests (IATs)

  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 two variations of the IAT, a suicide-related IAT and a Escape-Me IAT to determine the extent to which participants associate suicide-related and escape-related constructs with the self.

  Weeks 1, 3, and 5

Secondary Outcomes (8)

• Buss-Perry Aggression Questionnaire

  Weeks 1, 2, 3, 4, and 5

• Overt Aggression Scale Modified

  Weeks 1, 2, 3, 4, and 5

• Point Subtraction Aggression Paradigm

  Weeks 1, 3, and 5

• Barratt Impulsiveness Scale

  Weeks 1, 2, 3, 4, and 5

• Beck Scale for Suicidal Ideation

  Weeks 1, 2, 3, 4, and 5

Other Outcomes (4)

• Hamilton Depression Scale

  Weeks 1, 2, 3, 4, and 5

• Generalized Anxiety Disorder-7

  Weeks 1, 2, 3, 4, and 5

• Pittsburgh Sleep Quality Index

  Weeks 1, 2, 3, 4, and 5

Study Arms (1)

Suvorexant group

EXPERIMENTAL

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.

Drug: Suvorexant (dual orexin receptor antagonist)

Interventions

Suvorexant (dual orexin receptor antagonist) DRUG

Veteran patients with Major Depressive Disorder and elevated risk of suicide will receive the FDA-approved drug Suvorexant (brand name: Belsomra), a dual orexin receptor 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.

Suvorexant group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Marianne Goodman: lead
• James J. Peters Veterans Affairs Medical Center: collaborator

Study Sites (1)

James J. Peters Veterans Affairs Medical Center

The Bronx, New York, 10468, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

suvorexant; Orexin Receptor Antagonists

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Sleep Aids, Pharmaceutical; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Central Nervous System Agents; Therapeutic Uses

Central Study Contacts

Marianne Goodman, MD

CONTACT

718-584-9000; Marianne.Goodman@va.gov

James Murrough, MD, PhD

CONTACT

212-585-4640; James.Murrough@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychiatrist; VISN 2 MIRECC Director

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 3, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Locations

US (1)