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Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics

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ClinicalTrials.gov Identifier: NCT04955470
Recruitment Status : Not yet recruiting
First Posted : July 8, 2021
Last Update Posted : September 30, 2021
Sponsor:
Information provided by (Responsible Party):
Quynh Doan, University of British Columbia

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.

Condition or disease Intervention/treatment Phase
Suicidal Ideation Drug: Ketamine Injectable Solution Drug: Midazolam Injectable Solution Drug: Normal Saline 0.9% Injectable Solution Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics: a Pilot Randomized Controlled Trial
Estimated Study Start Date : November 1, 2021
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : November 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intravenous ketamine
Infusion of 0.5 mg/kg of ketamine, at maximum dose of 40 mg, over 40 minutes.
Drug: Ketamine Injectable Solution
A 10 mg/mL solution of ketamine will be infused over a 40 minute period at a dose of 0.05mg/kg.

Active Comparator: Intravenous midazolam
Infusion of 0.03 mg/kg of midazolam, at maximum dose of 2 mg, over 40 minutes.
Drug: Midazolam Injectable Solution
A 5 mg/mL solution of midazolam will be infused over a 40 minute period at a dose of 0.02 mg/kg.

Placebo Comparator: Intravenous saline
Infusion of 0.9% saline over 40 minutes.
Drug: Normal Saline 0.9% Injectable Solution
A 0.9% normal saline solution will be infused over a 40 minute period.




Primary Outcome Measures :
  1. Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 90 minutes post infusion ]
    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.

  2. Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 90 minutes post infusion ]
    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.

  3. Pragmatic questionnaire [ Time Frame: 90 minutes post infusion ]
    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.


Secondary Outcome Measures :
  1. Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
    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.

  2. Montgomery-Åsberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
    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.

  3. Pragmatic questionnaire [ Time Frame: 24 hours, 7-, 14-, 21-, and 28 days ]
    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.

  4. Blinding assessment [ Time Frame: 90 minutes post infusion ]
    The proportion of participants and research personnel that correctly identify treatment arm allocation.

  5. Enrolment rate [ Time Frame: 28-days ]
    Proportion of eligible patients that consent to participate, and proportion of participants that are lost to follow-up at 7-, 14-, 21-, and 28-days.

  6. Demographics [ Time Frame: 28-days ]
    Demographics of eligible patients who decline to participate in the study.

  7. Drug reactions [ Time Frame: 28-days ]
    Incidence and frequency of side effects and adverse events.



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

The study will enroll children and adolescents presenting with SI in the paediatric ED.

Inclusion Criteria:

  1. 10 to 17 years of age
  2. Respond "yes" to either question 1 (Passive Ideation) or 2 (Active Ideation) on the C-SSRS
  3. Respond "yes" to either questions 3 (Method), 4 (Intent), or 5 (Plan) on the C-SSRS
  4. Deemed acceptable and appropriate for admission to the on-site Child and Adolescent Psychiatry Emergency (CAPE) unit by a pediatric psychiatrist
  5. Normal vital signs for age and a normal neurological exam (no focal deficits or abnormalities), as per attending clinician

Exclusion Criteria:

  1. History of benzodiazepine or ketamine use in the past 5 years
  2. Previous diagnosis of schizophrenia or active psychosis as per the treating physician
  3. Clinically unstable, requires resuscitation or admission to a medical ward for stabilizing therapy (i.e., intensive care unit.)
  4. Intoxicated or delirious
  5. Suspected or confirmed pregnancy
  6. Taking medications that may contraindicate the use of ketamine
  7. Known allergy or sensitivity to ketamine or ketamine-like compounds
  8. Neuro-cognitive impairment that precludes informed consent, assent, or ability to self-report pain and satisfaction
  9. Inability to understand spoken and/or written English without the use of an interpreter
  10. Previous enrollment in this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04955470


Contacts
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Contact: Karly Stillwell (604) 875-2345 ext 3691 kstillwell@bcchr.ca
Contact: Tatsuma Hind, BSc txhind@student.ubc.ca

Locations
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Canada, British Columbia
BC Children's Hospital
Vancouver, British Columbia, Canada, V6H 3N1
Contact: Karly Stillwell    (604) 875-2345 ext 3691    kstillwell@bcchr.ca   
Principal Investigator: Quynh Doan, PhD MHSc MD         
Sponsors and Collaborators
University of British Columbia
Investigators
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Principal Investigator: Quynh Doan, PhD MHSc MD University of British Columbia
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Responsible Party: Quynh Doan, Pediatric Emergency Physician and Associate Professor, University of British Columbia
ClinicalTrials.gov Identifier: NCT04955470    
Other Study ID Numbers: H21-01433
First Posted: July 8, 2021    Key Record Dates
Last Update Posted: September 30, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Suicidal Ideation
Suicide
Self-Injurious Behavior
Behavioral Symptoms
Midazolam
Ketamine
Pharmaceutical Solutions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents