NCT04613453

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 13 Years – 17 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The main purpose of the study is to examine the safety, efficacy, response predictors, and post-treatment trajectory of adolescents with TRD and high suicide risk following a highly conservative repeat dosing ketamine infusion paradigm (four infusions of 0.5mg/kg each over two weeks) compared to an active control, midazolam. Those who are randomized to midazolam and remain ill have the option to cross-over to ketamine in the open phase. All participants will be followed closely for four months post-treatment and treated with standard of care depression treatment (medication management and cognitive behavioral therapy). Brain-based predictors of anti-suicidal responses will be assessed via connectome predictive modeling (CPM), examining functional brain circuits via fMRI before and after treatment. Given the unregulated use of ketamine in the community at widely varying doses and frequencies, the safety data gathered from this highly conservative repeat dosing paradigm is critical to inform the field about potential risks. Efficacy data at rapid, short-term, and intermediate-term (4 month) timepoints will be critical to determining whether a larger study is warranted in this population. The assessment of brain-based predictors of response through the integration of functional neuroimaging adds an important measure of biological engagement that will inform subsequent studies and stands to contribute towards the goal of personalized medicine (i.e. determining not only if a treatment works, but in whom). Aim 1: To evaluate the safety of treating adolescents with TRD at high suicide risk with a conservative repeat-dosing ketamine paradigm followed by standard of care treatment over 4 months. Hypothesis: We anticipate no untoward effects on medical outcomes (cardiovascular function and bladder health) or cognitive function (measured via Cogstate). Aim 2: To evaluate the 48-hour impact of ketamine on suicidal ideation compared to midazolam, and to identify connectome phenotypes predictive of ideation post-treatment. Hypothesis: Ketamine will reduce suicidal thinking (Columbia Suicide Rating Scale, recent ideation subscale) compared to midazolam. CPM will identify networks predictive of ideation, validated via k-fold or leave-one-out cross-validation within the sample. The network measures obtained at this fixed ketamine dose will inform the design of larger clinical trials. Aim 3 (exploratory): To describe the trajectory of suicidal thinking, depressive symptoms, and use of mental health resources in both ketamine responders and non-responders over 4 months. In July of this year (2024), the NIMH DSMB determined that Study 2000029003 will not be able to enroll enough individuals to be sufficiently powered to test the efficacy of Ketamine in treating adolescents with Major Depressive Disorder (MDD) and suicidal ideation (the primary aim of the study). Subsequently, the study was closed to enrollment

Conditions

• Adolescent Suicide
• Adolescent Depression

Interventions

Type	Name	Description
DRUG	Ketamine Infusion	Participants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes.
DRUG	Midazolam Infusion	Participants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes.

Timeline

• Start date: 2022-01-21
• Primary completion: 2024-07-31
• Completion: 2024-12-03
• First posted: 2020-11-03
• Last updated: 2025-08-26
• Results posted: 2025-08-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study