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Study of IV Ketamine for Emergency Department Treatment of Adolescent Suicidal Ideation

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: NCT05468840
Recruitment Status : Not yet recruiting
First Posted : July 21, 2022
Last Update Posted : July 21, 2022
Sponsor:
Information provided by (Responsible Party):
Michael Schlegelmilch, University of Ottawa

Tracking Information
First Submitted Date  ICMJE July 11, 2022
First Posted Date  ICMJE July 21, 2022
Last Update Posted Date July 21, 2022
Estimated Study Start Date  ICMJE December 2022
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2022)
Feasibility of the study as measured by the percentage of eligible of patients able to complete the study protocol. [ Time Frame: Baseline ]
Data analysis for feasibility will be descriptive in nature and there will be no formal hypothesis testing. The percentage of eligible patients who complete the study will be reported.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2022)
  • Baseline distribution of responses to the first 5 questions of Beck Scale for Suicidal Ideation (SSI5) [ Time Frame: Baseline ]
    Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the SSI5 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial. The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.
  • Baseline distribution of responses to the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10) [ Time Frame: Baseline ]
    Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the MADRS10 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial. The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.
  • Baseline distribution of responses to the suicide item (#9) from the Beck Depression Index (BDI9). [ Time Frame: Baseline ]
    Estimates of central tendency (mean) and variance (standard deviation) from participant responses to the BDI9 at baseline will be measured and reported. These parameters will aid with sample size estimates for the larger definitive trial. The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.
  • Baseline pragmatic assessment of the first 5 questions of the Beck Scale for Suicidal Ideation (SSI5), the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MADRS10), and the suicide item (#9) from the Beck Depression Index (BDI9). [ Time Frame: Baseline ]
    Pragmatic assessment of the tool validity by asking each participant, which of the three tools best captures how they are feeling at baseline.
  • Blinding assessment [ Time Frame: Baseline ]
    Blinding adequacy will be measured by asking each participant which intervention they think they received at the end of the 40 minute study drug infusion.
  • Treatment efficacy measured by the Beck Scale for Suicidal Ideation (SSI5) [ Time Frame: 40 minutes post treatment start ]
    Suicidal ideation severity at the end of the 40-minute medication infusion will be measured using SSI5. The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.
  • Treatment efficacy measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10) [ Time Frame: 40 minutes post treatment start ]
    Suicidal ideation severity at the end of the 40-minute medication infusion will be measured using MADRS10. The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.
  • Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9) [ Time Frame: 40 minutes post treatment start ]
    Suicidal ideation severity at the end of the 40-minute medication infusion will be measured using BDI9. The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.
  • Treatment durability measured by the Beck Scale for Suicidal Ideation (SSI5) [ Time Frame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start ]
    The durability of a treatment effect on suicidal ideation will be measured by SSI5 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start. The first 5 questions of Beck Scale for Suicidal Ideation (SSI5) is a five item questionnaire scored from 0 to 10, with higher scores indicating more severe suicidal ideation.
  • Treatment durability measured by the suicide item (#10) from the Montgomery-Asberg Depression Rating Scale (MARDS10) [ Time Frame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start ]
    The durability of a treatment effect on suicidal ideation will be measured by MADRS10 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start. The MADRS is a 10 item, 6-point, depression scale. Item 10 rates suicidal ideation from 0 (Enjoys life or takes it as it comes), to 6 (Explicit plans for suicide when there is an opportunity. Active preparations for suicide) with higher scores indicating more severe suicidal ideation.
  • Treatment efficacy measured by the suicide item (#9) from the Beck Depression Index (BDI9) [ Time Frame: 80 minutes, 120 minutes, 24 hours, and seven days post treatment start ]
    The durability of a treatment effect on suicidal ideation will be measured by BDI9 at 80 minutes, 120 minutes, 24 hours, and seven days post treatment start. The Beck Depression Inventory is a 21 item depression questionnaire. Item 9 rates suicidal ideation from 0 (I don't have thoughts of killing myself) to 3 (I would kill myself if I had the chance) with higher scores indicating more severe suicidal ideation.
  • Admission to Hospital [ Time Frame: 18 months ]
    The number and percentage of patients who require hospital admission at the enrolment ED visit will be reported.
  • Length of Stay in Hospital [ Time Frame: 18 months ]
    The mean and standard deviation of length of hospital stay for patients admitted at the enrolment visit will be reported.
  • Revisits to the ED [ Time Frame: 18 months ]
    The number and percentage of patients who require a repeat ED visit(s) for mental health complaints within 30 days following enrolment will be reported.
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 Study of IV Ketamine for Emergency Department Treatment of Adolescent Suicidal Ideation
Official Title  ICMJE A Double Blinded, Randomized, Placebo Controlled, Parallel Arm Pilot Trial of Intravenous Ketamine for Emergency Department Treatment of Suicidal Ideation in a Pediatric Population
Brief Summary

Approximately 20% of Canadian adolescents experience thoughts of suicide, or suicidal ideation (SI), and suicide is the second leading cause of death among Canadians aged 15-19 years. The emergency department at CHEO sees approximately four patients per day with SI. Even though this is a medical emergency, there are no fast-acting treatments available.

Ketamine is a medication that is commonly used to safely sedate children who require painful procedures in the emergency department. For nearly ten years, intravenous ketamine has also been shown to rapidly reduce SI in adults. However, ketamine as a treatment for SI has never been studied in adolescents. The primary study objective is to pilot a clinical trial that investigates intravenous ketamine to emergently treat SI in adolescents.

If intravenous ketamine can relieve symptoms of SI for youth, this would have tremendous effects on patients and would dramatically change how physicians treat adolescent mental health emergencies. If ketamine is effective for several weeks, as it is in adults, it will help temporize patients until they receive more long-term psychiatric care. At the system level, it has the potential to reduce emergency visits and lengthy admissions. The investigators feel that the results of this study will be generalizable to pediatric centres across Canada and beyond.

Detailed Description

Suicidal ideation (SI) is a common and often severe cause of morbidity in adolescents. Patients frequently present to the emergency department (ED) with severe and distressing thoughts of self-harm or suicide, and yet, there is currently no acute therapeutic intervention to offer them. The standard of care for patients who do not require admission is to discharge them home with resources for websites, apps, or telephone help lines. These interactions fail to address the underlying suicidal thoughts and leave patients, families and providers feeling very dissatisfied. Medications are nearly never initiated in the ED and patients who are already taking anti-depressants experience a very slow therapeutic onset, and often with unfavourable side effects that make medication compliance difficult and sometimes impossible.

For nearly ten years, intravenous ketamine has been shown to be an efficacious acute therapy in adult patients with suicidal ideation. A single dose of intravenous (IV) ketamine can rapidly reduce the severity of suicidal ideation by moderate to large effect sizes (Cohen's d = 0.5-0.8) during an ED visit, in an adult population. However, it has never been studied in a pediatric population. The study primary objective is to determine the feasibility of conducting a trial that investigates the efficacy of IV ketamine to reduce suicidal ideation in adolescents in the pediatric emergency department.

If intravenous ketamine can rapidly alleviate the severity of SI for adolescents, this would have tremendous effects on patients and families and dramatically change how ED physicians treat pediatric mental health emergencies. It would increase patient safety, reduce patient distress, morbidity, possibly mortality and alleviate family stress. If the therapeutic effect of ketamine is maintained for several days, as it is in adults, it will help temporize patient symptoms while they are connected with more long-term psychiatric care. At the system level, it may reduce rates of ED visits and, often lengthy, admissions to hospital. The investigators feel that the results of this study will be generalizable to pediatric centres across Ontario, Canada and beyond.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Suicidal Ideation
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    see study arm description
    Other Name: ketamine
  • Drug: Normal saline
    see study arm description
Study Arms  ICMJE
  • Experimental: Intravenous ketamine infusion
    Participants in the intervention group will receive 0.5mg/kg of 1mg/mL intravenous ketamine (50 mg maximum) over 40 minutes.
    Intervention: Drug: Ketamine Hydrochloride
  • Placebo Comparator: Intravenous normal saline infusion
    Participants in the control group will receive 0.5mL/kg intravenous normal saline (50 ml maximum) over 40 minutes.
    Intervention: Drug: Normal saline
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: July 20, 2022)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Responds "yes" to ASQ questionnaire at triage, which asks; "Are you having thoughts of killing yourself right now?"
  2. Moderate to severe suicidal ideation, defined as score ≥ 3 on the first 5 questions of the Beck Scale for Suicidal Ideation (SSI5)
  3. Age 12 to 17 years, inclusive
  4. Medically clear, as judged by the treating physician
  5. Speaks English or French

Exclusion Criteria

  1. Acute intoxication
  2. Previously enrolled in the current study or another clinical trial
  3. History of intellectual disability or autism spectrum disorder by patient/parent report
  4. Active, or history of, psychosis or psychotic disorder
  5. History of non-psychiatric neurologic disorder (e.g., epilepsy)
  6. Any of the following contraindications to ketamine based on the drug monograph:

    1. Known allergy or hypersensitivity to ketamine by patient history
    2. History of cerebrovascular accident (stroke or aneurysm)
    3. History of elevated intracranial pressure or idiopathic intracranial hypertension
    4. Significant hypertension requiring daily medication
    5. Severe cardiac decompensation
  7. On a Form 1
  8. Requires physical or chemical restraint
  9. History of violence while in hospital
  10. Assessment by a mental health practitioner during the current ED visit prior to study enrollment
  11. Pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Schlegelmilch, MD, MPH 1-613-737-7600 mschlegelmilch@cheo.on.ca
Contact: Maala Bhatt, MD, Msc mbhatt@cheo.on.ca
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05468840
Other Study ID Numbers  ICMJE 0000001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
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
Current Responsible Party Michael Schlegelmilch, University of Ottawa
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University of Ottawa
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Ottawa
Verification Date July 2022

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