Clinical trial NCT06854224: Orexin Antagonism for Suicide Risk: a Proof-of-Concept Clinical Trial
Official title: Orexin Antagonism to Target Mechanisms of Suicide Risk: a Proof-of-Concept Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Suicide Risk
Major Depressive Disorder (MDD)
Keywords: Suicide risk
Proof-of-concept clinical trial
Suvorexant
Orexin antagonist
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: VISN 2 Mental Illness Research & Education Clinical Center
First posted: 2025-03-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Suicide-related Implicit Association Test
timeFrame: Weeks 1, 3, and 5
Secondary outcomes:
measure: Buss-Perry Aggression Questionnaire
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Overt Aggression Scale Modified
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Point Subtraction Aggression Paradigm
timeFrame: Weeks 1, 3, and 5
measure: Barratt Impulsiveness Scale
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Beck Scale for Suicidal Ideation
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Go/No-go task
timeFrame: Weeks 1, 3, and 5
measure: Columbia Suicide Severity Rating Scale
timeFrame: Weeks 1, 2, 3, 4, and 5
Other outcomes:
measure: Hamilton Depression Scale
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Generalized Anxiety Disorder-7
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Pittsburgh Sleep Quality Index
timeFrame: Weeks 1, 2, 3, 4, and 5
measure: Patient-rated Inventory of Side-Effects
timeFrame: Weeks 1, 2, 3, 4, and 5
Locations:
city: Bronx
country: United States
facility: James J. Peters Veterans Affairs Medical Center
state: New York
Study officials:
References: