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Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy (SAD-KIDS)

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ClinicalTrials.gov Identifier: NCT03889756
Recruitment Status : Not yet recruiting
First Posted : March 26, 2019
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE March 22, 2019
First Posted Date  ICMJE March 26, 2019
Last Update Posted Date September 25, 2019
Estimated Study Start Date  ICMJE September 2019
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2019)
  • Evaluate the efficacy of a multiple-dosing ketamine infusion paradigm (2 infusions per week for 3 weeks) compared to midazolam in adolescents with treatment resistant depression [ Time Frame: Day 18 ]
    Establish if repeated ketamine will be efficacious medically and psychiatrically, as measured by a significant reduction in CDRS score in those treated with ketamine at the end of the dosing paradigm
  • Evaluate the tolerability of a multiple-dosing ketamine infusion paradigm (2 infusions per week for 3 weeks) compared to midazolam in adolescents with treatment resistant depression [ Time Frame: Day 18 ]
    Establish if repeated ketamine will be tolerated as measured by drop-out rates
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03889756 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy
Official Title  ICMJE Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy
Brief Summary The purpose of this study is to evaluate the intermediate-term efficacy and tolerability of a multiple-dosing ketamine infusion paradigm for the treatment of medication-refractory major depressive disorder (MDD). We are using a two-phase design. The first phase is a 3-week double blind parallel design clinical trial comparing 6 infusions of ketamine compared to 6 infusions of midazolam in 24 adolescents with treatment resistant depression. The primary outcome of this phase will be Children's Depression Rating Scale (CDRS) score at Day 18. The second phase is a 6-month open phase in which patients who received midazolam and remain depressed with be offered open ketamine treatment (6 infusions over 3 weeks). All participants will be followed weekly for 6 months and tracked for time to relapse.
Detailed Description The purpose of this study is to evaluate the intermediate-term efficacy and tolerability of a multiple-dosing ketamine infusion paradigm for the treatment of medication-refractory major depressive disorder (MDD). The specific aims of the study are: To evaluate the efficacy and tolerability of a multiple-dosing ketamine infusion paradigm (2 infusions per week for 3 weeks) compared to midazolam in adolescents with treatment resistant depression (TRD), . To test these aims we have designed a two-phase trial. The first phase is a 3-week double blind parallel design clinical trial comparing 6 infusions of ketamine compared to 6 infusions of midazolam in 24 adolescents with TRD. The primary outcome of this phase will be Children's Depression Rating Scale (CDRS) score at Day 18. The second phase is a 6-month open phase in which patients who received midazolam and remain depressed with be offered open ketamine treatment (6 infusions over 3 weeks). All participants will be followed weekly for 6 months and tracked for time to relapse. In those who initially responded to ketamine, symptom triggered maintenance infusions will be offered during this 6-month time period. All participants will receive standard of care treatment in addition to experimental procedures, and will be tracked monthly with extensive neurocognitive assessments.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Phase 1 is a double-blind, midazolam-controlled parallel design trial; Phase 2 is an open extension.
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
Participants will not be told what medication they are receiving; physicians absent from the infusion paradigm will perform blinded clinical efficacy ratings.
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: Ketamine infusion
    The dose of ketamine established in prior research (0.5 mg/kg over 40 minutes) will be used in this study to minimize risks. The maximum total single dose allowed in this study will be 40mg, corresponding to a weight of 80kg.
  • Drug: Midazolam infusion
    The weight-based midazolam dosing established in prior ketamine trials in adults (0.045mg/kg) will be used to minimize risks, as this is considered a very low dose compared to the sedation literature. The maximum total dose allowed in this study will be 3.6mg per infusion, corresponding to a weight of 80kg.
Study Arms  ICMJE
  • Experimental: Ketamine
    Ketamine is an FDA-approved anesthetic agent that is commonly used to induce surgical anesthesia due to its low incidence of significant respiratory depression and hypotension. It as a N-methyl-D-aspartate (NMDA) receptor antagonist and glutamatergic modulator, and has been demonstrated in multiple controlled clinical trials to have rapidly acting antidepressant and anti-suicidal effects in adults.
    Intervention: Drug: Ketamine infusion
  • Placebo Comparator: Midazolam
    Midazolam, the active control in this study, is a medication that is approved by the Food and Drug Administration as a sedative for both children and adults.It is a benzodiazepine with a short half-life that was chosen so as to blind the psychotomimetic effects of Ketamine.
    Intervention: Drug: Midazolam infusion
Publications *

*   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: March 22, 2019)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female ages 13-17 years
  2. Meet DSM-5 (Diagnostic and Statistical Manual 5 ) criteria for Major Depressive Disorder by structured interview (MINI-KID)
  3. Children's Depression Rating Scale, Revised CDRS score ≥40 at screening
  4. Failure to achieve remission with at least 2 antidepressant trials (e.g. SSRI, SNRI or TCA), meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing
  5. Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy.
  6. Medically and neurologically healthy on the basis of physical examination and medical history.
  7. Parents able to provide written informed consent and adolescents must additionally provide assent.

Exclusion Criteria:

  1. History of psychotic disorder, manic episode, autism spectrum disorder diagnosed by MINI-KID
  2. History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
  3. Intellectual disability (IQ<70) per medical history
  4. Pregnancy (urine pregnancy tests on the day of infusions for menstruating girls) or lactation
  5. Prior treatment with ketamine for depression or prior recreational use of ketamine.
  6. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David Zakur 203 785-6906 pedidepression@yale.edu
Contact: Jennifer Dwyer, MD 203 737-4809 jennifer.dwyer@yale.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03889756
Other Study ID Numbers  ICMJE 2000023857
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael H. Bloch, MD Yale University
Study Director: Jennifer Dwyer, MD Yale University
PRS Account Yale University
Verification Date September 2019

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