Adolescent SuicidePhase 2NCT04613453
Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine
A Phase 2 study testing Ketamine Infusion and Midazolam Infusion in people with Adolescent Suicide and Adolescent Depression, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to determine if intravenous ketamine reduces suicidal thinking compared to an active placebo (midazolam) in adolescents who have treatment resistant depression and a recent history of a suicide event (defined as a suicide attempt, emergency room evaluation for suicidal thinking, or a… Read more about this study
- Who is it for?
- Ages 13 to 17 years
- Conditions the study is for
- Adolescent Suicide, Adolescent Depression
- What is being tested?
- Ketamine Infusion and Midazolam Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jan 2022to 3 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Ages 13-17 years, inclusive
- Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID+)
- Children's Depression Rating Scale, Revised (CDRS-R) score ≥45 at screening
- Continued clinically significant depressive symptoms despite an SRI trial (e.g. SSRI or SNRI) of adequate dose and duration, meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing
- Suicide event within the past 120 days (i.e. a suicide attempt (defined as an act of potentially self-injurious behavior with explicit or inferred intent to die) -OR- degree of suicidal ideation requiring an emergency evaluation or a transition to higher level of care (e.g. intensive outpatient program, partial hospital program, inpatient)
- Columbia Suicide Severity Rating Scale ideation score of ≥ 1 at screening
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- Medically and neurologically healthy on the basis of physical examination, medical history, and the clinical judgement of the evaluating physician.
- Parents able to provide written informed permission and adolescents must additionally provide assent.
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Provision of signed and dated parental permission and adolescent assent form. If there are two parents or guardians, both must provide permission and each must sign a separate permission form.
Who cannot join
- History of psychotic disorder, manic episode, or 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 participation in a ketamine study, prior clinical psychiatric treatment with ketamine, or prior recreational use of ketamine
- Pre-existing cardiovascular disease or untreated or unstable hypertension
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- Body weight greater than 80 kgs
- Currently taking benzodiazepines or other medications that may cause respiratory depression, or lamotrigine, which is hypothesized to interfere with ketamine's mechanism of action
- Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines in English.
- For participation in the fMRI scans only (participants with contraindications to fMRI may still participate in all other portions of the trial, providing they meet all other inclusion/exclusion criteria):
- Any contraindication to MRI including severe claustrophobia, or metal in the body (including mental dental braces)
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
The purpose of this study is to determine if intravenous ketamine reduces suicidal thinking compared to an active placebo (midazolam) in adolescents who have treatment resistant depression and a recent history of a suicide event (defined as a suicide attempt, emergency room evaluation for suicidal thinking, or a transition to inpatient care for suicidality in the past 120 days).
The primary objective of this study is to determine whether ketamine reduces suicidal ideation (as measured via the C-SSRS, recent ideation scale) relative to an active control, midazolam, 48-hours after first administration in adolescents with TRD at high suicide risk.
Read the detailed description
The main purpose of the study is to examine the safety, efficacy, response predictors, and post-treatment trajectory of adolescents with TRD and high suicide risk following a highly conservative repeat dosing ketamine infusion paradigm (four infusions of 0.5mg/kg each over two weeks) compared to an active control, midazolam. Those who are randomized to midazolam and remain ill have the option to cross-over to ketamine in the open phase. All participants will be followed closely for four months post-treatment and treated with standard of care depression treatment (medication management and cognitive behavioral therapy). Brain-based predictors of anti-suicidal responses will be assessed via connectome predictive modeling (CPM), examining functional brain circuits via fMRI before and after treatment.
Given the unregulated use of ketamine in the community at widely varying doses and frequencies, the safety data gathered from this highly conservative repeat dosing paradigm is critical to inform the field about potential risks. Efficacy data at rapid, short-term, and intermediate-term (4 month) timepoints will be critical to determining whether a larger study is warranted in this population. The assessment of brain-based predictors of response through the integration of functional neuroimaging adds an important measure of biological engagement that will inform subsequent studies and stands to contribute towards the goal of personalized medicine (i.e. determining not only if a treatment works, but in whom).
Aim 1: To evaluate the safety of treating adolescents with TRD at high suicide risk with a conservative repeat-dosing ketamine paradigm followed by standard of care treatment over 4 months. Hypothesis: We anticipate no untoward effects on medical outcomes (cardiovascular function and bladder health) or cognitive function (measured via Cogstate).
Aim 2: To evaluate the 48-hour impact of ketamine on suicidal ideation compared to midazolam, and to identify connectome phenotypes predictive of ideation post-treatment. Hypothesis: Ketamine will reduce suicidal thinking (Columbia Suicide Rating Scale, recent ideation subscale) compared to midazolam. CPM will identify networks predictive of ideation, validated via k-fold or leave-one-out cross-validation within the sample. The network measures obtained at this fixed ketamine dose will inform the design of larger clinical trials.
Aim 3 (exploratory): To describe the trajectory of suicidal thinking, depressive symptoms, and use of mental health resources in both ketamine responders and non-responders over 4 months.
In July of this year (2024), the NIMH DSMB determined that Study 2000029003 will not be able to enroll enough individuals to be sufficiently powered to test the efficacy of Ketamine in treating adolescents with Major Depressive Disorder (MDD) and suicidal ideation (the primary aim of the study). Subsequently, the study was closed to enrollment
- Conditions
- Adolescent Suicide, Adolescent Depression
- Being tested
- Ketamine Infusion, Midazolam Infusion
- Keywords
- Intravenous Ketamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine InfusionDrug
Participants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes.
Midazolam InfusionDrug
Participants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine Infusion | Experimental | Participants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes. Receives: Drug: Ketamine Infusion |
| Midazolam Infusion | Active comparator | Participants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes. Receives: Drug: Midazolam Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Columbia-Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). Total score ranges for suicidal ideation from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent). Total score ranges for suicidal behavior from a minimum of 0 (corresponding to no suicidal behavior) to a maximum of 5 (representing active suicidal behavior).
Measured: Baseline and Day 3
Secondary outcomes (2)
Montgomery Asberg Depression Rating Scale
Montgomery Asberg Depression Rating Scale is an 10-item scale examines depressive symptoms and will be assessed at baseline (prior to any experimental treatment), prior to each experimental treatment, and weekly during the open phase of the trial. This 10-item scale ranges from 0 to 60, with higher values representing more intensive depressive symptoms.
Measured: Baseline and Day 3
Change in Children's Depression Rating Scale
Children's Depression Rating Scale-Revised is a 17-item scale examines depressive symptoms in children and adolescents using the combined report of the adolescent and the parent, synthesized by a clinician. It will be administered at baseline (prior to any experimental treatment), at the end of the blinded phase of the trial (Day 11), and monthly during the open phase of the trial. This 17-item clinical scale creates scores that range from 17 to 113, with higher scores representing more intensive depressive symptoms
Measured: Baseline to Day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2020
- Study start21 Jan 2022
- Primary completion31 Jul 2024
- Study completion3 Dec 2024
Why it stopped: Terminated early due to concerns from the NIH DSMB regarding the rate of recruitment and the resulting inability to accomplish the initially approved study aims
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adolescent SuicideStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael Bloch, Yale University
- Investigators
- Michael Bloch, MD MS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04613453
- Sponsor's protocol ID
- 2000029003
- Other IDs
- 1R01MH125203-01
- Status last verified
- Aug 2025
- First submitted
- 27 Oct 2020
- Last updated
- 26 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine
- ClinicalTrials.gov ID
- NCT04613453
- Acronym / sponsor ID
- 2000029003
- Conditions
- Adolescent Suicide, Adolescent Depression
- Keywords
- Intravenous Ketamine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated early due to concerns from the NIH DSMB regarding the rate of recruitment and the resulting inability to accomplish the initially approved study aims
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 21 Jan 2022 (actual)
- Primary completion
- 31 Jul 2024 (actual)
- Study completion
- 3 Dec 2024 (actual)
- First posted
- 3 Nov 2020 (actual)
- Results
- Posted 26 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if intravenous ketamine reduces suicidal thinking compared to an active placebo (midazolam) in adolescents who have treatment resistant depression and a recent history of a suicide event (defined as a suicide attempt, emergency room evaluation for suicidal thinking, or a transition to inpatient care for suicidality in the past 120 days).
The primary objective of this study is to determine whether ketamine reduces suicidal ideation (as measured via the C-SSRS, recent ideation scale) relative to an active control, midazolam, 48-hours after first administration in adolescents with TRD at high suicide risk.
Detailed description
The main purpose of the study is to examine the safety, efficacy, response predictors, and post-treatment trajectory of adolescents with TRD and high suicide risk following a highly conservative repeat dosing ketamine infusion paradigm (four infusions of 0.5mg/kg each over two weeks) compared to an active control, midazolam. Those who are randomized to midazolam and remain ill have the option to cross-over to ketamine in the open phase. All participants will be followed closely for four months post-treatment and treated with standard of care depression treatment (medication management and cognitive behavioral therapy). Brain-based predictors of anti-suicidal responses will be assessed via connectome predictive modeling (CPM), examining functional brain circuits via fMRI before and after treatment.
Given the unregulated use of ketamine in the community at widely varying doses and frequencies, the safety data gathered from this highly conservative repeat dosing paradigm is critical to inform the field about potential risks. Efficacy data at rapid, short-term, and intermediate-term (4 month) timepoints will be critical to determining whether a larger study is warranted in this population. The assessment of brain-based predictors of response through the integration of functional neuroimaging adds an important measure of biological engagement that will inform subsequent studies and stands to contribute towards the goal of personalized medicine (i.e. determining not only if a treatment works, but in whom).
Aim 1: To evaluate the safety of treating adolescents with TRD at high suicide risk with a conservative repeat-dosing ketamine paradigm followed by standard of care treatment over 4 months. Hypothesis: We anticipate no untoward effects on medical outcomes (cardiovascular function and bladder health) or cognitive function (measured via Cogstate).
Aim 2: To evaluate the 48-hour impact of ketamine on suicidal ideation compared to midazolam, and to identify connectome phenotypes predictive of ideation post-treatment. Hypothesis: Ketamine will reduce suicidal thinking (Columbia Suicide Rating Scale, recent ideation subscale) compared to midazolam. CPM will identify networks predictive of ideation, validated via k-fold or leave-one-out cross-validation within the sample. The network measures obtained at this fixed ketamine dose will inform the design of larger clinical trials.
Aim 3 (exploratory): To describe the trajectory of suicidal thinking, depressive symptoms, and use of mental health resources in both ketamine responders and non-responders over 4 months.
In July of this year (2024), the NIMH DSMB determined that Study 2000029003 will not be able to enroll enough individuals to be sufficiently powered to test the efficacy of Ketamine in treating adolescents with Major Depressive Disorder (MDD) and suicidal ideation (the primary aim of the study). Subsequently, the study was closed to enrollment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine Infusion | Experimental | Drug: Ketamine InfusionParticipants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes. |
| Midazolam Infusion | Active comparator | Drug: Midazolam InfusionParticipants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes. |
Who may qualify
- Ages
- 13 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- Ages 13-17 years, inclusive
- Meet DSM-5 criteria for Major Depressive Disorder by structured interview (MINI-KID+)
- Children's Depression Rating Scale, Revised (CDRS-R) score ≥45 at screening
- Continued clinically significant depressive symptoms despite an SRI trial (e.g. SSRI or SNRI) of adequate dose and duration, meaning at least 6 weeks at therapeutic dosing, including at least 4 weeks of stable dosing
- Suicide event within the past 120 days (i.e. a suicide attempt (defined as an act of potentially self-injurious behavior with explicit or inferred intent to die) -OR- degree of suicidal ideation requiring an emergency evaluation or a transition to higher level of care (e.g. intensive outpatient program, partial hospital program, inpatient)
Key exclusion criteria (11 listed)
- History of psychotic disorder, manic episode, or 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 participation in a ketamine study, prior clinical psychiatric treatment with ketamine, or prior recreational use of ketamine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine InfusionParticipants will receive four Ketamine infusions over two weeks, each 0.5mg/kg over 40 minutes. | Drug | Ketamine Infusion |
| Midazolam InfusionParticipants will receive four Midazolam infusions over two weeks, each 0.045mg/kg over 40 minutes. | Drug | Midazolam Infusion |
Primary outcome
Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: Baseline and Day 3
The C-SSRS is an assessment of suicidal ideation and behavior in clinical and research settings. The C-SSRS consists of 16 questions that ask about suicidal ideation and behaviors (the first 10 questions comprise the ideation subscale and the last 6 comprise the behavior subscale). Total score ranges for suicidal ideation from a minimum of 0 (corresponding to no suicidal ideation) to a maximum of 5 (representing active suicidal ideation with plan and intent). Total score ranges for suicidal behavior from a minimum of 0 (corresponding to no suicidal behavior) to a maximum of 5 (representing active suicidal behavior).
2 secondary outcomes
Montgomery Asberg Depression Rating Scale
Time frame: Baseline and Day 3
Change in Children's Depression Rating Scale
Time frame: Baseline to Day 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Bloch, MD MS principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine Infusion and Midazolam Infusion in people with Adolescent Suicide and Adolescent Depression, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Columbia-Suicide Severity Rating Scale (C-SSRS) (time frame: Baseline and Day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2025.