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Ketamine Infusion for Adolescent Depression and Anxiety

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ClinicalTrials.gov Identifier: NCT02579928
Recruitment Status : Completed
First Posted : October 20, 2015
Results First Posted : March 16, 2020
Last Update Posted : July 14, 2020
Sponsor:
Collaborator:
American Academy of Child Adolescent Psychiatry.
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE October 16, 2015
First Posted Date  ICMJE October 20, 2015
Results First Submitted Date  ICMJE December 5, 2019
Results First Posted Date  ICMJE March 16, 2020
Last Update Posted Date July 14, 2020
Study Start Date  ICMJE October 2015
Actual Primary Completion Date September 28, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion [ Time Frame: 1 day after the infusion ]
Depressive symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) on 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal /symptom absent. 7 to 19 - mild depression. 20 to 34 - moderate depression. >34 - severe depression.
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
Improvement in depressive symptoms [ Time Frame: 1 day after the infusion ]
Our primary outcome will be improvement in depressive symptoms as measured by Children's Depression Rating Scale, revised (CDRS-R) score, 1 day after infusion.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Ketamine metabolites and D-serine [ Time Frame: 40 minutes (end of the infusion), 80 minutes, 110 minutes, and 230 minutes after each infusion ]
    Plasma levels
  • Risk of suicidality [ Time Frame: Scored at Screening, 60 minutes before each infusion, 180 minutes after each infusion,at Day 1 /Day1+14, Day 2/Day 2 +14, Day 3/Day 3 + 14, Day5/ Day 5+14, Day 7/ Day 7+14, Day 10/ Day 10+14 and Day 14/ Day 14 + 14 ]
    Assessment with the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine Infusion for Adolescent Depression and Anxiety
Official Title  ICMJE Efficacy of Rapid-Acting NMDA Antagonist for Treatment of Adolescent Depression and Anxiety Disorders
Brief Summary The purpose of this study is to determine the tolerability and short-term efficacy of a single ketamine infusion for the treatment of adolescents with 1) medication-refractory major depressive disorder (MDD) and/or 2) medication-refractory anxiety disorders (social anxiety disorder, panic disorder, generalized anxiety disorder and/or separation anxiety disorder).
Detailed Description We will conduct a crossover trial in which as many as 36 adolescents (18 with MDD and 18 with anxiety disorders) will be given a single infusion of ketamine (study drug) or midazolam (active control). MDD symptoms and anxiety symptoms will be monitored over a two-week period. If applicable, comorbid school refusal symptoms will also be monitored over a two-week period for both cohorts. A 2-week washout period will be required between infusion doses. Our primary outcomes will be 1) improvement in MDD symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial and 2) improvement in the anxiety symptoms (measured by the Multimodal Anxiety Scale for Children (MASC) acute physical symptoms subscale) for the cohort of subjects enrolled in the anxiety disorders arm of the trial.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Participants were randomly assigned the treatment order, with participants receiving a single infusion of either ketamine hydrochloride (0.5 mg/kg) or midazolam (0.045 mg/kg) on Day 1, and the alternate compound 2 weeks later.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Midazolam was chosen as an active placebo in keeping with its similar pharmacokinetic profile and precedent as a reasonable comparator for nonspecific behavioral effects of ketamine
Primary Purpose: Treatment
Condition  ICMJE
  • Major Depressive Disorder
  • Anxiety Disorder
Intervention  ICMJE
  • Drug: Ketamine
    A single dose of 0.5mg/kg of Ketamine will be administered Intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.
    Other Name: Ketalar
  • Drug: Midazolam
    A single dose of 0.045mg/kg of Midazolam will be administered intravenously during 40 minutes in the Hospital Research Unit of YNHH. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.
    Other Name: Versed
Study Arms  ICMJE
  • Experimental: Ketamine
    Participants were randomly be assigned to receive a dose of 0.5 mg/kg of Ketamine (administered intravenously over 40 minutes with a maximum total dose allowed in this study will be 50mg).
    Intervention: Drug: Ketamine
  • Experimental: Midazolam
    Participants were randomly assigned to receive a dose of 0.045mg/kg of Midazolam (administered Intravenously over 40 minutes with a the maximum total dose allowed in this study of 4.5mg),
    Intervention: Drug: Midazolam
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 Completed
Actual Enrollment  ICMJE
 (submitted: March 2, 2020)
17
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2015)
18
Actual Study Completion Date  ICMJE September 2019
Actual Primary Completion Date September 28, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

MDD Cohort:

  • Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID)
  • CDRS-R score >40.
  • Failure to achieve remission with at least 1 adequate prior antidepressant trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.

Anxiety Cohort:

  • Meet DSM-5 criteria for any of the following anxiety disorders: Social Anxiety Disorders, Generalized Anxiety Disorder, Separation Anxiety Disorder and/or Panic Disorder by structured interview (MINI-KID)
  • ADIS Clinical Severity Rating ≥4 (moderately severe) for any of the 4 included anxiety disorders
  • Failure to achieve remission with at least 1 adequate prior anxiolytic medication trial (e.g. SSRI, SNRI, or TCA), meaning at least 8 weeks at therapeutic dosing, including at least 4 weeks of stable dosing.
  • Failure to achieve remission with previous CBT or subject declines current CBT therapy

Both cohorts:

  • Stable psychiatric medications and doses for the month prior to enrollment. Subjects may continue to engage in any ongoing psychotherapy.
  • Medically and neurologically healthy on the basis of physical examination and medical history.
  • Parents able to provide written informed consent and adolescents must additionally provide assent.

Exclusion:

  • Current inpatient hospitalization or active suicidal ideation requiring referral for inpatient hospitalization for safety.
  • History of psychotic disorder or manic episode diagnosed by MINI-KID
  • History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
  • Pregnancy (urine pregnancy tests on the day of scans for menstruating girls).
  • 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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02579928
Other Study ID Numbers  ICMJE 1506016041
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE American Academy of Child Adolescent Psychiatry.
Investigators  ICMJE
Principal Investigator: Michael H. Bloch, MD MS Yale University
PRS Account Yale University
Verification Date June 2020

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