Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics (Keta4SI)
Primary Purpose
Suicidal Ideation
Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Ketamine Injectable Solution
Midazolam Injectable Solution
Normal Saline 0.9% Injectable Solution
Sponsored by
About this trial
This is an interventional treatment trial for Suicidal Ideation
Eligibility Criteria
The study will enroll children and adolescents presenting with SI in the paediatric ED.
Inclusion Criteria:
- 10 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
Exclusion Criteria:
- 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
- No parent/guardian present.
Sites / Locations
- BC Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Intravenous ketamine
Intravenous midazolam
Intravenous saline
Arm Description
Infusion of 0.5 mg/kg of ketamine, at maximum dose of 40 mg, over 40 minutes.
Infusion of 0.03 mg/kg of midazolam, at maximum dose of 2 mg, over 40 minutes.
Infusion of 0.9% saline over 40 minutes.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
Blinding assessment
The proportion of participants and research personnel that correctly identify treatment arm allocation.
Enrolment rate
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.
Demographics
Demographics of eligible patients who decline to participate in the study.
Drug reactions
Incidence and frequency of side effects and adverse events.
Full Information
NCT ID
NCT04955470
First Posted
June 21, 2021
Last Updated
November 3, 2022
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT04955470
Brief Title
Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics
Acronym
Keta4SI
Official Title
Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics: a Pilot Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suicidal Ideation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
96 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intravenous ketamine
Arm Type
Experimental
Arm Description
Infusion of 0.5 mg/kg of ketamine, at maximum dose of 40 mg, over 40 minutes.
Arm Title
Intravenous midazolam
Arm Type
Active Comparator
Arm Description
Infusion of 0.03 mg/kg of midazolam, at maximum dose of 2 mg, over 40 minutes.
Arm Title
Intravenous saline
Arm Type
Placebo Comparator
Arm Description
Infusion of 0.9% saline over 40 minutes.
Intervention Type
Drug
Intervention Name(s)
Ketamine Injectable Solution
Intervention Description
A 10 mg/mL solution of ketamine will be infused over a 40 minute period at a dose of 0.05mg/kg.
Intervention Type
Drug
Intervention Name(s)
Midazolam Injectable Solution
Intervention Description
A 5 mg/mL solution of midazolam will be infused over a 40 minute period at a dose of 0.02 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Normal Saline 0.9% Injectable Solution
Intervention Description
A 0.9% normal saline solution will be infused over a 40 minute period.
Primary Outcome Measure Information:
Title
Columbia Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
90 minutes post infusion
Title
Montgomery-Åsberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
90 minutes post infusion
Title
Pragmatic questionnaire
Description
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.
Time Frame
90 minutes post infusion
Secondary Outcome Measure Information:
Title
Columbia Suicide Severity Rating Scale (C-SSRS)
Description
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.
Time Frame
24 hours
Title
Montgomery-Åsberg Depression Rating Scale (MADRS)
Description
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.
Time Frame
24 hours, 7-, 14-, 21-, and 28 days
Title
Pragmatic questionnaire
Description
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.
Time Frame
24 hours, 7-, 14-, 21-, and 28 days
Title
Blinding assessment
Description
The proportion of participants and research personnel that correctly identify treatment arm allocation.
Time Frame
90 minutes post infusion
Title
Enrolment rate
Description
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.
Time Frame
28-days
Title
Demographics
Description
Demographics of eligible patients who decline to participate in the study.
Time Frame
28-days
Title
Drug reactions
Description
Incidence and frequency of side effects and adverse events.
Time Frame
28-days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
The study will enroll children and adolescents presenting with SI in the paediatric ED.
Inclusion Criteria:
10 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
Exclusion Criteria:
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
No parent/guardian present.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karly Stillwell
Phone
(604) 875-2345
Ext
3691
Email
kstillwell@bcchr.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Tatsuma Hind, BSc
Email
txhind@student.ubc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Quynh Doan, PhD MHSc MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
BC Children's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3N1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karly Stillwell
Phone
(604) 875-2345
Ext
3691
Email
kstillwell@bcchr.ca
First Name & Middle Initial & Last Name & Degree
Quynh Doan, PhD MHSc MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics
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