Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04592809
Recruitment Status : Not yet recruiting
First Posted : October 19, 2020
Last Update Posted : March 9, 2021
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE September 29, 2020
First Posted Date  ICMJE October 19, 2020
Last Update Posted Date March 9, 2021
Estimated Study Start Date  ICMJE May 2021
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2020)
Number of participants with suicidal event, which is defined as suicide attempt, or emergency department visit, or inpatient hospitalization due to suicidality [ Time Frame: 12 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2020)
  • Death/Suicide Implicit Association Test (IAT) [ Time Frame: 2 weeks ]
    The IAT is a performance-based measure of cognition that has demonstrated good reliability and sensitivity to change. The IAT measures associations based on response latency where the response time is compared across categorization tasks.
  • Depression symptoms as measured by CHRT-SR a self report measure [ Time Frame: 2 weeks ]
    (specify for each) Concise Health Risk Tracking Self-Report (CHRT-SR) consists of 14 questions with responses ranging from 0 (strongly disagree) to 4 (strongly agree). 1) the Propensity subscale, which consists of 9 questions and 4 factors (pessimism, helplessness, social support, and despair) and a score range of 0-36; and the Suicidal Thoughts subscale, which consists of 3 questions and a score range of 0-9 (which will serve as the primary suicidal behavior outcome in this study); and 3) Impulsivity, which consists of 2 questions and a score range of 0-6. A total score is also calculated, ranging from 0 to 56.
  • Number of participants with suicidal events/behaviors as measured by CHRT-C a self report measure [ Time Frame: 2 week ]
    Concise Health Risk Tracking Clinician-Rated Behavior Module (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. a yes on any of the 9 questions indicates presence of suicidal event/behaviors (ideation, attempt, preparatory acts, non suicidal self injury, other injury).
  • Depression symptoms as measured by QIDS-A-SR, self report measure [ Time Frame: 2 weeks ]
    Quick Inventory of Depressive Symptomatology - Adolescent, Self-Report (QIDS-A-SR) is a depressive symptom severity measure that rates all nine criterion symptoms of MDD. A score of 0-51 will be calculated, with 51 indicating the highest severity.
  • Depression symptoms as measured by QIDS-A-SR, Parent report measure [ Time Frame: 2 weeks ]
    Quick Inventory of Depressive Symptomatology - Adolescent, Parent Report (QIDS-A-SR) is a depressive symptom severity measure that rates all nine criterion symptoms of MDD. A score of 0-51 will be calculated, with 51 indicating the highest severity.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents
Official Title  ICMJE Double-Blind Randomized Controlled Trial of Acute-Course of Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents
Brief Summary The study design is a double-blind, randomized, active-control trial of adolescents (ages 12-18 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.
Detailed Description

Youth patients (ages 12-18) who have recent suicidality (defined as suicidal ideation or behavior), and who are enrolled or expected to be enrolled in an intensive outpatient program (IOP) will be recruited for participation in the study. Upon informed consent/assent, baseline data will be collected regarding mood symptoms, suicidal ideation and behavior, associated comorbidities, and treatment history. Youth participants will be randomized to ketamine or midazolam, which will be provided twice weekly for two weeks. Participants will then have follow-up assessments visits through week 12 to continue to monitor outcomes. Participants may be recruited directly from the IOP or from the ED or inpatient psychiatric unit, provided they have undergone evaluation and are confirmed to begin IOP treatment. The baseline visit and first infusion must be +/- 10 days of IOP enrollment.

Enrollment of 264 subjects is expected to take place over a period of approximately 36 months. Enrolled participants will be involved in the study for approximately 14 weeks (screening plus 12 weeks of study follow-up visits). Visits include a Screening Visit, a Baseline, 4 Study Intervention Visits, and 10 Follow-Up Visits. Multiple streams of outcome measures will be utilized for this protocol, including self-report measures, research assessor-completed measures, clinic level measures, and behavioral measures.

Aim 1. Evaluate reduction in frequency of suicidal events associated with two-week twice-weekly course of ketamine treatment versus midazolam.

Aim 2. Evaluate reduction in implicit suicidal cognition with ketamine.

Aim 3. Evaluate reduction in depressive symptoms and suicidality with ketamine.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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).
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

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.

Primary Purpose: Treatment
Condition  ICMJE
  • Suicide, Attempted
  • Suicide and Depression
  • Suicide Threat
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    infused over a 40 minute period
    Other Name: Ketalar
  • Drug: Midazolam Hydrochloride
    infused over a 40 minute period
    Other Name: Versed
Study Arms  ICMJE
  • Active Comparator: Ketamine
    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.
    Interventions:
    • Drug: Ketamine Hydrochloride
    • Drug: Midazolam Hydrochloride
  • Active Comparator: Midazolam
    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.
    Interventions:
    • Drug: Ketamine Hydrochloride
    • Drug: Midazolam Hydrochloride
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 12, 2020)
264
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2024
Estimated Primary Completion Date February 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Be adolescents (aged 12-18 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 30 days);
  • Be admitted (or plan to be admitted within 10 days) to IOP;
  • Have a current primary diagnosis of depression based on the K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia) (other psychiatric disorders are acceptable, but must not be primary);
  • Be able to complete assessments in English.

Exclusion Criteria:

  • Have lifetime schizophrenia, psychotic disorder, pervasive developmental disorder, or mental retardation;
  • Have current mania, hypomania, or mixed episode, or obsessive compulsive disorder;
  • Have a primary diagnosis other than depression
  • Have moderate to severe alcohol or substance use disorder within the past six months (based on K-SADS-PL);
  • If female, be pregnant, lactating, or nursing;
  • Have unstable medical conditions or with clinically significant laboratory or ECG values;
  • Be at serious suicidal risk that cannot be managed in the IOP setting;
  • Have been enrolled in the IOP for more than 10 days;
  • Have prior treatment with or contraindications to ketamine or esketamine.
  • Adolescents currently being treated with stimulant medication or benzodiazepines will be evaluated by the study physician to determine if the type and dose of concomitant medication, and will be excluded if the concomitant medication could substantially increase the risk of study infusion.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Maria Monastirsky, MSW 2146480174 Maria.Monastirsky@UTSouthwestern.edu
Contact: Taryn Mayes, MA 214-648-0158 Taryn.Mayes@UTSouthwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04592809
Other Study ID Numbers  ICMJE STU-2020-0973
R01MH125181 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Madhukar Trivedi, MD University of Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP