Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine Infusion for Adolescent Depression and Anxiety

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02579928
Recruitment Status : Active, not recruiting
First Posted : October 20, 2015
Last Update Posted : August 15, 2019
Sponsor:
Collaborator:
American Academy of Child Adolescent Psychiatry.
Information provided by (Responsible Party):
Yale University

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).

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Anxiety Disorder Drug: Ketamine Drug: Midazolam Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Rapid-Acting NMDA Antagonist for Treatment of Adolescent Depression and Anxiety Disorders
Study Start Date : October 2015
Actual Primary Completion Date : September 28, 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anxiety

Arm Intervention/treatment
Experimental: Ketamine
A dose of 0.5 mg/kg of Ketamine will be administered intravenously over 40 minutes. The maximum total dose allowed in this study will be 50mg.
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

Active Comparator: Midazolam
A dose of 0.045mg/kg of Midazolam will be administered Intravenously over 40 minutes. The maximum total dose allowed in this study will be 4.5mg.
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




Primary Outcome Measures :
  1. Improvement in depressive symptoms [ Time Frame: 1 day after the infusion ]
    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

  2. Improvement in anxiety [ Time Frame: 1 day after the infusion ]
    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.


Secondary Outcome Measures :
  1. 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

  2. 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)

  3. Effect on school refusal behavior [ Time Frame: Scored at Screening, prior to each infusion, and 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 ]
    Examine ketamine's effects on school-refusal behavior (SRB) that is associated with anxiety and depression using the School Refusal Assessment Scale Child and Parent versions



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   13 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT02579928


Locations
Layout table for location information
United States, Connecticut
Hospital Research Unit at the Yale New Haven Hospital
New Haven, Connecticut, United States, 06510
Yale Child Study Center
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
American Academy of Child Adolescent Psychiatry.
Investigators
Layout table for investigator information
Principal Investigator: Michael H. Bloch, MD MS Yale University

Publications:
Layout table for additonal information
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02579928     History of Changes
Other Study ID Numbers: 1506016041
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
Keywords provided by Yale University:
Ketamine
Depression
Major Depressive Disorder
Anxiety
School refusal
Suicide
Generalized Anxiety
Suicidal Ideation
Additional relevant MeSH terms:
Layout table for MeSH terms
Disease
Depression
Depressive Disorder
Anxiety Disorders
Depressive Disorder, Major
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Midazolam
Ketamine
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