Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

NCT04592809 | Completed Phase 3 FDA Drug

• 2 other identifiers: STU-2020-0973R01MH125181
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This project aims to examine the signal of efficacy of ketamine, a rapidly acting medication shown to decrease suicidality in adults in as short as hours or days, as opposed to weeks. The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants must be receiving standard of care treatment which may range broadly from both outpatient and inpatient programs which include clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.

Conditions

Suicide, Attempted; Suicide and Depression; Suicide Threat

Keywords

depression; adolescent; suicidal ideation; suicide attempt; teen; child; intensive outpatient; inpatient hospitalization; depression treatment; suicide treatment

Outcome Measures

Primary Outcomes (1)

• The primary outcome for the study is "suicidal events". Suicidal event is defined as a suicide attempt, or emergency department visit or inpatient hospitalization due to suicidality.

  Concise Health Risk Tracking Clinician-Rated Behavior Module (CHRT-C) will be used to identify suicidal events. The CHRT-C consists of nine clinician-rated yes/no items about specific behaviors (i.e., suicidal ideation, suicidal attempt, preparatory acts, non-suicidal self-injury (NSSI), other injuries, etc.). At the initial administration, this instrument captures lifetime information; at subsequent administrations, it will capture information since the last visit.

  12 weeks

Secondary Outcomes (4)

• Death/Suicide Implicit Association Test (IAT)

  2 weeks

• Depression symptoms as measured by CHRT-SR a self report measure

  2 weeks

• Number of participants with suicidal events/behaviors as measured by CHRT-C a self report measure

  2 week

• Depression symptoms as measured by the Inventory of Depressive Symptomatology (IDS), self-report measure

  2 weeks

Study Arms (2)

Ketamine

ACTIVE COMPARATOR

0.5 mg/kg intravenous ketamine will be administered 4 times in a 2 week period. Ketamine will be dissolved in 0.9% sodium chloride in a total volume of 100ml and administered with a syringe infusion pump at a constant rate.

Drug: Ketamine Hydrochloride; Drug: Midazolam Hydrochloride

Midazolam

ACTIVE COMPARATOR

0.02 mg/kg midazolam will be administered 4 times in a 2 week period. Midazolam will be dissolved in 0.9% sodium chloride in a total volume of 100ml and administered with a syringe infusion pump at a constant rate.

Drug: Ketamine Hydrochloride; Drug: Midazolam Hydrochloride

Interventions

Ketamine Hydrochloride DRUG

infused over a 40 minute period

Also known as: Ketalar

Ketamine; Midazolam

Midazolam Hydrochloride DRUG

infused over a 40 minute period

Also known as: Versed

Ketamine; Midazolam

Eligibility Criteria

• Age: 13 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Study participants must:
• Be adolescents (aged 13-18 years);
• Have had a recent suicidal event (suicide attempt or significant suicidal ideation with a plan or intent warranting emergency evaluation or inpatient hospitalization within the past 90 days);
• Receiving standard of care treatment that includes clinically indicated psychosocial and/or psychopharmacological treatment;
• Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other psychiatric disorders are acceptable, but must not be primary);
• Participants must be able to complete assessments in English. However, the parent(s) or legal guardians of minors may either speak English or Spanish
• Use effective method of contraception during and for 90 days following the end of treatment for female and male participants. Recommended methods of birth control are namely, consistent use of an approved hormonal birth control (pill/patches, rings), an intrauterine device (IUD), contraceptive injection, double barrier methods, sexual abstinence, or sterilization;

You may not qualify if:

• Study participants must not:
• Have a psychotic disorder, such as lifetime schizophrenia, or a pervasive or intellectual developmental disorder requiring substantial or very substantial support;
• Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
• Have a primary diagnosis other than a depressive disorder;
• Have moderate to severe alcohol or substance use disorder within the past six months (based on MINI-KID); If there is a positive urine drug screen at screening, the urine drug screen will be repeated at each infusion visit. Positive urine drug screen will be reviewed by study physician and infusion will proceed as long as no safety risk was identified;
• If female, be pregnant, lactating, or nursing; Women of childbearing potential must have a negative urine pregnancy test prior to all infusions;
• Have unstable medical conditions (stable for less than 3 months) or with clinically significant laboratory values or an electrocardiogram (ECG) that would pose significant risk;
• Be at serious suicidal risk that cannot be managed in the outpatient setting;
• Have prior treatment for depression with or contraindications to ketamine, esketamine, or, midazolam;
• Weigh \>120 kilograms at baseline. If participants are enrolled but exceed 120 kilograms at any time during the treatment period, they will be removed from the treatment portion of the study.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

MeSH Terms

Conditions

Suicide, Attempted; Suicide; Depression; Suicidal Ideation

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Madhukar Trivedi, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The investigator, patient, and study staff will be blinded. Packaging and labeling of the study drugs will be performed by the research pharmacy in a way to ensure blinding throughout the study. No members of the study team will have access to the randomization scheme during the conduct of the study. The Research Pharmacist and the CDRC (Center for Depression Research and Clinical Care) Program Manager will have access to the treatment assignment in the event of an emergency. The treatment code must not be broken except in medical emergencies when the appropriate management of the patient necessitates knowledge of the treatment randomization. The investigator retains the right to break the code for serious adverse events (SAEs) that are unexpected and are suspected to be causally related to a study drug and that potentially require expedited reporting to regulatory authorities.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Youth will be randomized in 1:1 fashion to either intravenous ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg) twice weekly for 2 weeks followed by weekly visits for 10 weeks (for a total of 12-week post-randomization observation period).

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 19, 2020
• Study Start: October 3, 2022
• Primary Completion: July 1, 2025
• Study Completion: August 31, 2025
• Last Updated: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)