Clinical TrialSuicidalityKetamineCompleted

Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

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 will be treated through a suicide prevention IOP (typically 6-8 weeks), as well as 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.

Target Enrollment
114 participants
Study Type
Phase III interventional
Design
Randomized, triple Blind

Detailed Description

Randomised, triple-blind, active-controlled Phase III trial in adolescents (13–18 years) with recent suicidal behaviour comparing IV ketamine 0.5 mg/kg versus midazolam 0.02 mg/kg. Four infusions over two weeks with follow-up to 12 weeks.

Primary aims are to evaluate reduction in repeat suicidal events and implicit suicidal cognition with ketamine; secondary outcomes include depressive symptoms, safety, and functional measures. Participants receive standard of care treatment alongside study infusions.

Study Protocol

Preparation

sessions

Dosing

4 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

IV ketamine 0.5 mg/kg infused over 40 minutes; four infusions over 2 weeks.

Interventions

  • Ketamine0.5 mg/kg
    via IV• twice weekly for 2 weeks• 4 doses total

    Infused over 40 minutes in 100 ml 0.9% sodium chloride.

Midazolam

active comparator

IV midazolam 0.02 mg/kg infused over 40 minutes; four infusions over 2 weeks.

Interventions

  • Compound0.02 mg/kg
    via IV• twice weekly for 2 weeks• 4 doses total

    Midazolam Hydrochloride (Versed) infused over 40 minutes; active comparator.

Participants

Ages
12 – 18
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria
  • Study participants must:
  • 1. Be adolescents (aged 13-18 years);
  • 2. 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);
  • 3. Receiving standard of care treatment that includes clinically indicated psychosocial and/or psychopharmacological treatment;
  • 4. Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other psychiatric disorders are acceptable, but must not be primary);
  • 5. Participants must be able to complete assessments in English. However, the parent(s) or legal guardians of minors may either speak English or Spanish;
  • 6. Use effective method of contraception during and for 90 days following the end of treatment for female and male participants.

Exclusion Criteria

  • Exclusion Criteria
  • Study participants must not:
  • 1. Have a psychotic disorder, such as lifetime schizophrenia, or a pervasive or intellectual developmental disorder requiring substantial or very substantial support;
  • 2. Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
  • 3. Have a primary diagnosis other than a depressive disorder;
  • 4. 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;
  • 5. If female, be pregnant, lactating, or nursing; Women of childbearing potential must have a negative urine pregnancy test prior to all infusions;
  • 6. 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;
  • 7. Be at serious suicidal risk that cannot be managed in the outpatient setting;
  • 8. Have prior treatment for depression with or contraindications to ketamine, esketamine, or, midazolam;
  • 9. Treatment with medications that may alter pharmacokinetics of ketamine, including moderate-to-strong inhibitors or inducers of CYP3A4 and CYP2B6, is exclusionary. Regarding pharmacodynamic interactions, medications that may increase heart rate or blood pressure such as the ADHD stimulant medications will be permitted with last dose at least 24 hours prior to infusion. All concomitant medications will be evaluated by the study physician to determine if the type and dose of concomitant medication requires discontinuation and will be excluded if the concomitant medication could substantially increase the risk of study infusion. A complete list of medications that are Not Allowed is available in Appendix D of the protocol. The study team will not ask the participant to discontinue any treatment (except for not taking ADHD medications for 24 hours before study treatment) just for the sake of taking part in this study;
  • 10. 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.

Study Details

  • Status
    Completed
  • Phase
    Phase III
  • Type
    interventional
  • Design
    Randomizedtriple Blind
  • Target Enrollment114 participants
  • Timeline
    Start: 2021-01-05
    End: 2024-01-02
  • Compound
    Ketamine
  • Topic
    Suicidality

Locations

UT Southwestern Medical Center — Dallas, Texas, United States

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