Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics

NCT04955470 | Terminated Phase 1 DMC

• 1 other identifier: H21-01433
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Suicide is a leading cause of death for children and adolescents. Since warning signs of suicide and links to precipitating events differ between age groups, suicide can be difficult to predict. As a result, children often seek care for suicidal ideation (SI) in the emergency department (ED) where a limited number of treatment options exist. Current psychotherapies and pharmacotherapies, such as antidepressants, provide benefit over weeks or months and thus limits their effective application in the ED. Consequently, when there is an imminent threat to the child's safety, the typical management solution is to admit the patient to a safe environment and hopefully de-escalate over time. To address a more rapid-onset treatment option for SI, a number of studies in adults have suggested that a single, sub-anesthetic dose of intravenous ketamine can rapidly reduce depression and SI severity. These results are promising, but large-scale trials are needed to determine if ketamine is a safe and effective treatment for acute suicidality in the pediatric population. This approach has the benefit of working rapidly, avoiding involuntary hospitalizations, and protecting patients from self-harm until they can be connected to longer term mental health resources. This study will compare the use of intravenous ketamine to both active and placebo controls in children 10 to 17 years of age presenting to the pediatric ED for SI. The primary objective of this pilot trial is to explore the adequacy and range of three instruments measuring suicidality and to determine the sample size required for a large definitive randomized control trial. This larger trial will be used to estimate the effectiveness of intravenous ketamine for reducing SI in children in the pediatric ED. The secondary objectives are to assess study feasibility and optimize study procedures. Given very few side effects reported in adult studies and the relatively benign nature of those reported, the investigators do not expect any major safety concerns in the study.

Conditions

Suicidal Ideation

Outcome Measures

Primary Outcomes (3)

• Columbia Suicide Severity Rating Scale (C-SSRS)

  The CSSR-S is 6-point scale that measures SI severity via clinical interviews, ranging from 1 (wish to be dead) to 5 (suicidal intent with plan). Adolescents who deny any SI receive a 0. The distribution of "yes" responses on questions 3, 4, or 5 will be assessed from baseline. Higher scores indicate greater SI severity.

  90 minutes post infusion

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  The MADRS is a 10-item, 6-point scale that screens for depressive symptoms in adults via clinical interviews. A self-reported version (MADRS-self assessment) which has been validated in adolescents will be used, but only the final item that is specific to SI (item 10) will be asked. The distribution of scores from 0 to 6 will be assessed from baseline. Higher scores indicate greater SI severity.

  90 minutes post infusion

• Pragmatic questionnaire

  The pragmatic questionnaire is a brief, one sentence question designed to assess change in SI. Participants will be asked "How suicidal do you feel on a scale of 0 to 10?". The distribution of scores from 0 to 10 will be assessed from baseline. Higher scores indicate greater SI severity.

  90 minutes post infusion

Secondary Outcomes (7)

• Columbia Suicide Severity Rating Scale (C-SSRS)

  24 hours

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  24 hours, 7-, 14-, 21-, and 28 days

• Pragmatic questionnaire

  24 hours, 7-, 14-, 21-, and 28 days

• Blinding assessment

  90 minutes post infusion

• Enrolment rate

  28-days

Study Arms (3)

Intravenous ketamine

EXPERIMENTAL

Infusion of 0.5 mg/kg of ketamine, at maximum dose of 40 mg, over 40 minutes.

Drug: Ketamine Injectable Solution

Intravenous midazolam

ACTIVE COMPARATOR

Infusion of 0.03 mg/kg of midazolam, at maximum dose of 2 mg, over 40 minutes.

Drug: Midazolam Injectable Solution

Intravenous saline

PLACEBO COMPARATOR

Infusion of 0.9% saline over 40 minutes.

Drug: Normal Saline 0.9% Injectable Solution

Interventions

Ketamine Injectable Solution DRUG

A 10 mg/mL solution of ketamine will be infused over a 40 minute period at a dose of 0.05mg/kg.

Intravenous ketamine

Midazolam Injectable Solution DRUG

A 5 mg/mL solution of midazolam will be infused over a 40 minute period at a dose of 0.02 mg/kg.

Intravenous midazolam

Normal Saline 0.9% Injectable Solution DRUG

A 0.9% normal saline solution will be infused over a 40 minute period.

Intravenous saline

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• to 17 years of age
• Respond "yes" to either question 1 (Passive Ideation) or 2 (Active Ideation) on the C-SSRS
• Respond "yes" to either questions 3 (Method), 4 (Intent), or 5 (Plan) on the C-SSRS
• Deemed acceptable and appropriate for admission to the on-site Child and Adolescent Psychiatry Emergency (CAPE) unit by a pediatric psychiatrist
• Successful completion of Capacity to Assent.
• Normal vital signs for age and a normal neurological exam (no focal deficits or abnormalities), as per attending clinician

You may not qualify if:

• History of benzodiazepine or ketamine use in the past 3 months (ample wash out period)
• Lifetime history of ketamine or benzodiazepine use disorder
• Previous diagnosis of schizophrenia or active psychosis as per the treating physician
• Lifetime history of schizoaffective disorder
• Current hypomania, mania, mixed state
• Clinically unstable, requires resuscitation or admission to a medical ward for stabilizing therapy (i.e., intensive care unit.)
• History of cerebrovascular accident, uncontrolled seizure disorder, increased intracranial pressure
• Uncontrolled hypertension, low or labile blood pressure, severe cardiac decompensation
• Moderate to severe hepatic/renal impairment
• Intoxicated or delirious
• Suspected or confirmed pregnancy or women who are breastfeeding
• Known allergy or sensitivity to ketamine and/or midazolam or any component in the formulation.
• Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
• Inability to understand spoken and/or written English without the use of an interpreter
• Previous enrollment in this study

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

BC Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

MeSH Terms

Conditions

Suicidal Ideation

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Quynh Doan, PhD MHSc MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Emergency Physician and Associate Professor

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: July 8, 2021
• Study Start: June 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: October 1, 2023
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)