Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine

NCT04613453 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 20000290031R01MH125203-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if intravenous ketamine reduces suicidal thinking compared to an active placebo (midazolam) in adolescents who have treatment resistant depression and a recent history of a suicide event (defined as a suicide attempt, emergency room evaluation for suicidal thinking, or a transition to inpatient care for suicidality in the past 120 days). The primary objective of this study is to determine whether ketamine reduces suicidal ideation (as measured via the C-SSRS, recent ideation scale) relative to an active control, midazolam, 48-hours after first administration in adolescents with TRD at high suicide risk.

Conditions

Adolescent Suicide; Adolescent Depression

Keywords

Intravenous Ketamine

Outcome Measures

Primary Outcomes (1)

• Columbia-Suicide Severity Rating Scale (C-SSRS)

  The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). Total score ranges for suicidal ideation from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent). Total score ranges for suicidal behavior from a minimum of 0 (corresponding to no suicidal behavior) to a maximum of 5 (representing active suicidal behavior).

  Baseline and Day 3

Secondary Outcomes (2)

• Montgomery Asberg Depression Rating Scale

  Baseline and Day 3

• Change in Children's Depression Rating Scale

  Baseline to Day 11

Study Arms (2)

Ketamine Infusion

EXPERIMENTAL

Participants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes.

Drug: Ketamine Infusion

Midazolam Infusion

ACTIVE COMPARATOR

Participants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes.

Drug: Midazolam Infusion

Interventions

Ketamine Infusion DRUG

Participants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes.

Ketamine Infusion

Midazolam Infusion DRUG

Participants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes.

Midazolam Infusion

Eligibility Criteria

• Age: 13 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Ages 13-17 years, inclusive
• Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID+)
• Children's Depression Rating Scale, Revised (CDRS-R) score ≥45 at screening
• Continued clinically significant depressive symptoms despite an SRI trial (e.g. SSRI or SNRI) of adequate dose and duration, meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing
• Suicide event within the past 120 days (i.e. a suicide attempt (defined as an act of potentially self-injurious behavior with explicit or inferred intent to die) -OR- degree of suicidal ideation requiring an emergency evaluation or a transition to higher level of care (e.g. intensive outpatient program, partial hospital program, inpatient)
• Columbia Suicide Severity Rating Scale ideation score of ≥ 1 at screening
• Medically and neurologically healthy on the basis of physical examination, medical history, and the clinical judgement of the evaluating physician.
• Parents able to provide written informed permission and adolescents must additionally provide assent.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Provision of signed and dated parental permission and adolescent assent form. If there are two parents or guardians, both must provide permission and each must sign a separate permission form.

You may not qualify if:

• History of psychotic disorder, manic episode, or autism spectrum disorder diagnosed by MINI-KID
• History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology
• Intellectual disability (IQ\<70) per medical history
• Pregnancy (urine pregnancy tests on the day of infusions for menstruating girls) or lactation
• Prior participation in a ketamine study, prior clinical psychiatric treatment with ketamine, or prior recreational use of ketamine
• Pre-existing cardiovascular disease or untreated or unstable hypertension
• Body weight greater than 80 kgs
• Currently taking benzodiazepines or other medications that may cause respiratory depression, or lamotrigine, which is hypothesized to interfere with ketamine's mechanism of action
• Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.
• Any contraindication to MRI including severe claustrophobia, or metal in the body (including mental dental braces)

Sponsors & Collaborators

• Yale University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Results Point of Contact

• Title: Brooke Rivera
• Organization: Yale University

Brooke.rivera@yale.edu

203-974-2241

Study Officials

• Michael Bloch, MD MS

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: November 3, 2020
• Study Start: January 21, 2022
• Primary Completion: July 31, 2024
• Study Completion: December 3, 2024
• Last Updated: August 26, 2025
• Results First Posted: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)