Clinical TrialSuicidalityKetaminePlaceboTerminated

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

Phase II randomised, quadruple-blind trial (n=12 actual) comparing four IV ketamine infusions (0.5 mg/kg each over 40 minutes across two weeks) versus midazolam in adolescents (13–17) with TRD and recent suicide event to assess reduction in suicidal ideation.

Target Enrollment
12 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomised, parallel-group trial testing a conservative repeat-dosing ketamine paradigm (four 0.5 mg/kg IV infusions over two weeks) against an active comparator (midazolam 0.045 mg/kg) in adolescents with treatment-resistant depression and recent suicidal events.

Primary efficacy outcome is suicidal ideation (C-SSRS recent ideation) at 48 hours; participants receive standard of care treatment including medication management and cognitive behavioural therapy and are followed for four months. Functional MRI before and after treatment will be used to identify connectome phenotypes predictive of response.

Midazolam-randomised participants who remain ill may cross-over to open-label ketamine; safety assessments include cardiovascular monitoring, bladder health, and cognitive testing (Cogstate).

Study Protocol

Preparation

sessions

Dosing

4 sessions
40 min each

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Ketamine

experimental

Four IV ketamine infusions (0.5 mg/kg) over 40 minutes each across two weeks.

Interventions

  • Ketamine0.5 mg/kg
    via IV• four infusions over two weeks• 4 doses total

    Each infusion administered over 40 minutes.

Midazolam

active comparator

Four IV midazolam infusions (0.045 mg/kg) over 40 minutes across two weeks; option to cross-over to ketamine for non-responders in open phase.

Interventions

  • Placebo0.045 mg/kg
    via IV• four infusions over two weeks• 4 doses total

    Midazolam active comparator; non-responders may cross-over to open-label ketamine.

Participants

Ages
13 – 17
Sexes
Male & Female

Inclusion Criteria

  • 1. Ages 13-17 years, inclusive
  • 2. Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID+)
  • 3. Children's Depression Rating Scale, Revised (CDRS-R) score ≥45 at screening
  • 4. Continued clinically significant depressive symptoms despite an SRI trial of adequate dose and duration (≥6 weeks, including ≥4 weeks stable dosing)
  • 5. Suicide event within the past 120 days (suicide attempt, emergency evaluation for suicidal thinking, or transition to higher level of care)
  • 6. Columbia Suicide Severity Rating Scale ideation score ≥1 at screening
  • 7. Medically and neurologically healthy per exam and clinician judgement
  • 8. Parents able to provide written informed permission and adolescents provide assent
  • 9. Willingness to comply with study procedures and availability for study duration
  • 10. Provision of signed and dated parental permission and adolescent assent (both parents sign if two guardians)

Exclusion Criteria

  • 1. History of psychotic disorder, manic episode, or autism spectrum disorder diagnosed by MINI-KID
  • 2. History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology
  • 3. Intellectual disability (IQ <70) per medical history
  • 4. Pregnancy or lactation (urine pregnancy tests on day of infusions for menstruating participants)
  • 5. Prior participation in a ketamine study, prior clinical ketamine treatment, or prior recreational ketamine use
  • 6. Pre-existing cardiovascular disease or untreated/unstable hypertension
  • 7. Body weight greater than 80 kg
  • 8. Current use of benzodiazepines or other medications that may cause respiratory depression, or lamotrigine
  • 9. Inability to provide written informed consent per Yale HIC guidelines in English
  • 10. For fMRI participation only: any contraindication to MRI (eg severe claustrophobia, metal in body, dental braces)

Study Details

  • Status
    Terminated
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Randomizedquadruple Blind
  • Target Enrollment12 participants
  • Timeline
    Start: 2022-01-21
    End: 2025-03-31
  • Compounds
    KetaminePlacebo
  • Topic
    Suicidality

Locations

Yale New Haven Hospital — New Haven, Connecticut, United States

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