- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03889756
Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy (SAD-KIDS)
March 31, 2023 updated by: Yale University
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
3
Phase
- Phase 2
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale Child Study Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
11 years to 15 years (Child)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Male or female ages 13-17 years
- Meet DSM-5 (Diagnostic and Statistical Manual 5 ) criteria for Major Depressive Disorder by structured interview (MINI-KID)
- Children's Depression Rating Scale, Revised CDRS score ≥40 at screening
- 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
- 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 Criteria:
- History of psychotic disorder, manic episode, autism spectrum disorder diagnosed by MINI-KID
- History of substance dependence diagnosis by MINI-KID (excluding tobacco) or positive urine toxicology.
- Intellectual disability (IQ<70) per medical history
- Pregnancy (urine pregnancy tests on the day of infusions for menstruating girls) or lactation
- Prior treatment with ketamine for depression or prior recreational use of ketamine.
- Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of a Multiple-dosing Ketamine Infusion Paradigm (2 Infusions Per Week for 3 Weeks) Compared to Midazolam in Adolescents With Treatment Resistant Depression Using the Children's Depression Rating Scale (CDRS)
Time Frame: Day 18
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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.
The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale.
A rating of 1 indicates normal, thus the minimum score is 17.
The maximum score is 113.
Scores of 20-30 suggest borderline depression.
Scores of 40-60 indicate moderate depression.
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Day 18
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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
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Establish if repeated ketamine will be tolerated as measured by drop-out counts.
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Day 18
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Michael H. Bloch, MD, Yale University
- Study Director: Jennifer Dwyer, MD, Yale University
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006 Aug;63(8):856-64. doi: 10.1001/archpsyc.63.8.856.
- Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.
- Richmond TK, Rosen DS. The treatment of adolescent depression in the era of the black box warning. Curr Opin Pediatr. 2005 Aug;17(4):466-72. doi: 10.1097/01.mop.0000166347.53102.e7.
- Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.
- Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. A Survey of the Clinical, Off-Label Use of Ketamine as a Treatment for Psychiatric Disorders. Am J Psychiatry. 2017 Jul 1;174(7):695-696. doi: 10.1176/appi.ajp.2017.17020239. No abstract available.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 17, 2019
Primary Completion (Actual)
December 18, 2019
Study Completion (Actual)
January 5, 2023
Study Registration Dates
First Submitted
March 22, 2019
First Submitted That Met QC Criteria
March 22, 2019
First Posted (Actual)
March 26, 2019
Study Record Updates
Last Update Posted (Actual)
April 24, 2023
Last Update Submitted That Met QC Criteria
March 31, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Behavioral Symptoms
- Mental Disorders
- Mood Disorders
- Depression
- Depressive Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Ketamine
- Midazolam
Other Study ID Numbers
- 2000023857
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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