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Trial record 10 of 840 for:    Ketamine

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 : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Ketamine infusion Drug: Midazolam infusion Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
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
Official Title: Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy
Estimated Study Start Date : August 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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.

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.
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.




Primary Outcome Measures :
  1. 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

  2. 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



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

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.

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): NCT03889756


Contacts
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Contact: David Zakur 203 785-6906 david.zakur@yale.edu
Contact: Jennifer Dwyer, MD 203 737-4809 jennifer.dwyer@yale.edu

Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Michael H. Bloch, MD Yale University

Publications:
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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT03889756     History of Changes
Other Study ID Numbers: 2000023857
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yale University:
depression, ketamine

Additional relevant MeSH terms:
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Ketamine
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Midazolam
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
GABA Agents