Suicidal IdeationPhase 2/3NCT06891300
Understanding and Treating Suicidal Ideation With Ketamine
A Phase 2/3 study testing ketamine hydrochloride in people with Suicidal Ideation and Major Depressive Disorder (MDD), run by The Royal's Institute of Mental Health Research at 1 site in Canada.
Trial summary
The goal of this clinical trial is to treat active suicidal ideation in individuals with Major Depressive Disorder (MDD) using ketamine and to understand suicidal ideation by examining biological mechanisms using magnetic resonance imaging (MRI), and psychological mechanisms through validated clinical scales and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Suicidal Ideation, Major Depressive Disorder (MDD)
- What is being tested?
- ketamine hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- 8 Apr 2025to Oct 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- English speaking
- Ages 18-65 years old
- Suicidal ideation severity score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSRS) (Baseline/Screening version) at Screening Visit ("active suicidal ideation with any methods")
- Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5)
- Willing to maintain stable doses of concomitant medications throughout the study
- Be under the care of a designated health care provider (i.e., family physician or psychiatrist) to follow their care after the completion of the study.
Who cannot join
- Participants not medically cleared to receive ketamine treatment due to presence of clinically relevant disease (e.g., uncontrolled hypertension, renal or hepatic impairment, significant coronary artery disease, diabetes mellitus, seizure disorder).
- Known or suspected hypersensitivity or intolerance to ketamine
- Body mass index (BMI) ≥35
- History of a primary psychotic disorder (e.g., schizophrenia), or current or recent (<2 years) acute episode of psychosis
- Current and/or recent history (<12 months) of substance use/dependence (except for caffeine or nicotine) or problematic current alcohol use or dependence as defined by DSM-5 criteria
- Pregnant, breastfeeding or of childbearing potential and unwilling to use an approved method of contraception during the study
Show all 10Show fewer
- History of significant head injury including loss of consciousness >5 minutes
- Any MRI contraindications
- Concurrent use of ketamine in any form
- Concurrent active ECT or repetitive transcranial magnetic stimulation (rTMS) therapy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Royal Ottawa Mental Health Centre
Ottawa, Ontario, K1Z7K4
Research Coordinator, 613-722-6521 ext. 6934, suzannah.wojcik@theroyal.ca
Jennifer Phillips, PhD
About this study
Official title: Understanding and Treating Suicidal Ideation With Ketamine: A Diffusion Magnetic Resonance Imaging Study
The goal of this clinical trial is to treat active suicidal ideation in individuals with Major Depressive Disorder (MDD) using ketamine and to understand suicidal ideation by examining biological mechanisms using magnetic resonance imaging (MRI), and psychological mechanisms through validated clinical scales and qualitative interviews. The main questions it aims to answer are:
- Will ketamine will reduce suicidal ideation in a significant proportion of study participants?
- Will reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers?
Participants will receive four intravenous (IV) ketamine infusions administered twice weekly for two weeks. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting ketamine treatment, and 2) 24 hours after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. Qualitative interviews will occur within 72 hours after the fourth ketamine treatment.
Read the detailed description
This innovative, mixed-method study will combine treatment, neuroimaging, and qualitative interview approaches in a clinical sample enriched for suicide-related outcomes and selected for the presence of active suicidal thoughts. For study participants, ketamine may offer a rapid strategy to alleviate suicidal ideation and provide a window of opportunity to engage in other, longer-term strategies to decrease suicide risk. Collecting longitudinal diffusion MRI data while patients undergo ketamine treatment will further the understanding of the key brain circuitry involved in suicidal ideation, and the mechanisms underlying ketamine's antisuicidal effects. This work may identify new targets for intervention and suicide prevention. Finally, seeking patient perspectives on their change in suicidal thinking with ketamine may allow them to gain insight into their own thought patterns and how they change with lessening of suicidal ideation. These unique findings have the potential to inform future research directions, provide support for existing theories of suicide, and may even lead to new theories.
The overarching goal of this project is to treat active suicidal ideation in patients with MDD using ketamine and to harness ketamine's rapid antisuicidal effects to understand suicidal ideation by examining biological mechanisms using MRI, and psychological mechanisms through validated clinical scales and qualitative interviews.
The central hypothesis is that ketamine will reduce suicidal ideation in a significant proportion of study participants and that reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers assessed using advanced diffusion MRI.
The specific aims of the study are to:
- Measure changes in advanced diffusion MRI biomarkers (white matter microstructure, extracellular free water, and neurite density index) pre-post repeated ketamine treatment in association with changes in suicidal ideation.
- Link changes in suicidal ideation pre-post ketamine treatment with changes in suicide-related psychological features including hopelessness, psychological pain, and perceived burdensomeness.
- Explore patient perceptions of change in suicidal ideation while undergoing ketamine treatment through qualitative interviews.
This phase III, prospective, longitudinal study involves clinical assessment, neuroimaging, and qualitative interviews in participants undergoing repeated IV ketamine treatment for active suicidal ideation. The study is open-label and non-randomized. There is no use of a comparative agent. Participants will receive four IV ketamine infusions administered twice weekly for two weeks. Ketamine infusions will be administered at the BMO Innovative Clinic for Depression, a facility within the Royal Ottawa Mental Health Centre (ROMHC) that has safely administered over 500 intranasal esketamine treatments. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting treatment, and 2) 24 hours (+/-6 hours) after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. A short qualitative interview will occur within 72 hours after the fourth ketamine treatment. Each participants study duration is expected to be approximately 3 weeks total. The entire study will enroll participants over an 18 month period. Anticipated start date is MAR 2025 and anticipated end date is JAN 2026.
Thirty-six (36) participants will be recruited into the study. Systematic reviews and meta-analyses of the acute antisuicidal effects of ketamine report medium-large and large effect sizes. Despite calls for the reporting of standardized effect sizes in neuroimaging studies, existing preliminary diffusion MRI studies failed to report effect sizes for changes observed post-ketamine treatment. Nevertheless, assuming a medium effect size (Cohen's d=0.5), 80% power, a p value of 0.05, a power calculation shows a total sample size of 34 will allow detection of the primary outcome, pre-post treatment change in free water corrected fractional anisotropy. This sample size will inform future work. Early withdrawals will be replaced with new enrollments to allow 36 participants to complete the study.
The study team has extensive experience with longitudinal trials, and minimal attrition rate of participants is anticipated as the provision of treatment is expected to increase retention. Allowances have been made for participant withdrawal, incidental findings, or incomplete data by targeting a large enough sample size to inform future trials.
- Conditions
- Suicidal Ideation, Major Depressive Disorder (MDD)
- Being tested
- ketamine hydrochloride
- Keywords
- Major Depressive Disorder, Suicidal Ideation, Ketamine, Neuroimaging
- Medical subject headings
- Suicidal Ideation, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ketamine hydrochlorideDrug
Participants will undergo intravenous (IV) ketamine infusions (0.5 mg/kg infused over 40 minutes) under medical supervision. Treatments will be administered twice weekly for two weeks, for a total of four infusions.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants will undergo a total of four IV ketamine infusions (0.5 mg/kg infused over 40 minutes), administered twice weekly for two weeks. Receives: Drug: ketamine hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in white matter microstructure from pre-treatment to post-treatment, assessed via MRI.
Change in white matter microstructure (free water corrected fractional anisotropy) from pre-treatment to 24 hours post-treatment.
Measured: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Secondary outcomes (2)
Change in extracellular free water from pre-treatment to post-treatment, assessed via MRI.
Change in extracellular free water pre-post repeated ketamine infusions.
Measured: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Change in neurite density index from pre-treatment to post-treatment, assessed via MRI.
Change in neurite density index pre-post repeated ketamine infusions.
Measured: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start8 Apr 2025
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Royal's Institute of Mental Health Research
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Phillips, The Royal's Institute of Mental Health Research
- Investigators
- Jennifer Phillips, PhD, Principal investigator, University of Ottawa Institute for Mental Health Research at The Royal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06891300
- Sponsor's protocol ID
- REB 0216
- Other IDs
- ECR-1-119-23
- Status last verified
- Apr 2026
- First submitted
- 12 Mar 2025
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD collected and stored within the Cardio-Neuro-Mind Data Platform (CNMDP) to which data sharing consent has been provided by the individual participant.
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding and Treating Suicidal Ideation With Ketamine: A Diffusion Magnetic Resonance Imaging Study
- ClinicalTrials.gov ID
- NCT06891300
- Acronym / sponsor ID
- REB 0216
- Conditions
- Suicidal Ideation, Major Depressive Disorder (MDD)
- Keywords
- Major Depressive Disorder, Suicidal Ideation, Ketamine, Neuroimaging
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- The Royal's Institute of Mental Health ResearchUniversity, hospital or other
- Study start
- 8 Apr 2025 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 24 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to treat active suicidal ideation in individuals with Major Depressive Disorder (MDD) using ketamine and to understand suicidal ideation by examining biological mechanisms using magnetic resonance imaging (MRI), and psychological mechanisms through validated clinical scales and qualitative interviews. The main questions it aims to answer are:
- Will ketamine will reduce suicidal ideation in a significant proportion of study participants?
- Will reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers?
Participants will receive four intravenous (IV) ketamine infusions administered twice weekly for two weeks. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting ketamine treatment, and 2) 24 hours after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. Qualitative interviews will occur within 72 hours after the fourth ketamine treatment.
Detailed description
This innovative, mixed-method study will combine treatment, neuroimaging, and qualitative interview approaches in a clinical sample enriched for suicide-related outcomes and selected for the presence of active suicidal thoughts. For study participants, ketamine may offer a rapid strategy to alleviate suicidal ideation and provide a window of opportunity to engage in other, longer-term strategies to decrease suicide risk. Collecting longitudinal diffusion MRI data while patients undergo ketamine treatment will further the understanding of the key brain circuitry involved in suicidal ideation, and the mechanisms underlying ketamine's antisuicidal effects. This work may identify new targets for intervention and suicide prevention. Finally, seeking patient perspectives on their change in suicidal thinking with ketamine may allow them to gain insight into their own thought patterns and how they change with lessening of suicidal ideation. These unique findings have the potential to inform future research directions, provide support for existing theories of suicide, and may even lead to new theories.
The overarching goal of this project is to treat active suicidal ideation in patients with MDD using ketamine and to harness ketamine's rapid antisuicidal effects to understand suicidal ideation by examining biological mechanisms using MRI, and psychological mechanisms through validated clinical scales and qualitative interviews.
The central hypothesis is that ketamine will reduce suicidal ideation in a significant proportion of study participants and that reduction in suicidal ideation will be accompanied by rapid changes in neuroimaging biomarkers assessed using advanced diffusion MRI.
The specific aims of the study are to:
- Measure changes in advanced diffusion MRI biomarkers (white matter microstructure, extracellular free water, and neurite density index) pre-post repeated ketamine treatment in association with changes in suicidal ideation.
- Link changes in suicidal ideation pre-post ketamine treatment with changes in suicide-related psychological features including hopelessness, psychological pain, and perceived burdensomeness.
- Explore patient perceptions of change in suicidal ideation while undergoing ketamine treatment through qualitative interviews.
This phase III, prospective, longitudinal study involves clinical assessment, neuroimaging, and qualitative interviews in participants undergoing repeated IV ketamine treatment for active suicidal ideation. The study is open-label and non-randomized. There is no use of a comparative agent. Participants will receive four IV ketamine infusions administered twice weekly for two weeks. Ketamine infusions will be administered at the BMO Innovative Clinic for Depression, a facility within the Royal Ottawa Mental Health Centre (ROMHC) that has safely administered over 500 intranasal esketamine treatments. Participants will undergo two identical MRI scans: 1) within 48 hours prior to starting treatment, and 2) 24 hours (+/-6 hours) after the fourth ketamine infusion. Suicidal ideation and depressive symptoms will be assessed prior to each imaging session alongside additional self-report measures. A short qualitative interview will occur within 72 hours after the fourth ketamine treatment. Each participants study duration is expected to be approximately 3 weeks total. The entire study will enroll participants over an 18 month period. Anticipated start date is MAR 2025 and anticipated end date is JAN 2026.
Thirty-six (36) participants will be recruited into the study. Systematic reviews and meta-analyses of the acute antisuicidal effects of ketamine report medium-large and large effect sizes. Despite calls for the reporting of standardized effect sizes in neuroimaging studies, existing preliminary diffusion MRI studies failed to report effect sizes for changes observed post-ketamine treatment. Nevertheless, assuming a medium effect size (Cohen's d=0.5), 80% power, a p value of 0.05, a power calculation shows a total sample size of 34 will allow detection of the primary outcome, pre-post treatment change in free water corrected fractional anisotropy. This sample size will inform future work. Early withdrawals will be replaced with new enrollments to allow 36 participants to complete the study.
The study team has extensive experience with longitudinal trials, and minimal attrition rate of participants is anticipated as the provision of treatment is expected to increase retention. Allowances have been made for participant withdrawal, incidental findings, or incomplete data by targeting a large enough sample size to inform future trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: ketamine hydrochlorideParticipants will undergo a total of four IV ketamine infusions (0.5 mg/kg infused over 40 minutes), administered twice weekly for two weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- English speaking
- Ages 18-65 years old
- Suicidal ideation severity score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSRS) (Baseline/Screening version) at Screening Visit ("active suicidal ideation with any methods")
- Diagnosis of Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5)
- Willing to maintain stable doses of concomitant medications throughout the study
Key exclusion criteria (10 listed)
- Participants not medically cleared to receive ketamine treatment due to presence of clinically relevant disease (e.g., uncontrolled hypertension, renal or hepatic impairment, significant coronary artery disease, diabetes mellitus, seizure disorder).
- Known or suspected hypersensitivity or intolerance to ketamine
- Body mass index (BMI) ≥35
- History of a primary psychotic disorder (e.g., schizophrenia), or current or recent (<2 years) acute episode of psychosis
- Current and/or recent history (<12 months) of substance use/dependence (except for caffeine or nicotine) or problematic current alcohol use or dependence as defined by DSM-5 criteria
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 hydrochlorideParticipants will undergo intravenous (IV) ketamine infusions (0.5 mg/kg infused over 40 minutes) under medical supervision. Treatments will be administered twice weekly for two weeks, for a total of four infusions. | Drug | Ketamine |
Primary outcome
Change in white matter microstructure from pre-treatment to post-treatment, assessed via MRI.
Time frame: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Change in white matter microstructure (free water corrected fractional anisotropy) from pre-treatment to 24 hours post-treatment.
2 secondary outcomes
Change in extracellular free water from pre-treatment to post-treatment, assessed via MRI.
Time frame: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Change in neurite density index from pre-treatment to post-treatment, assessed via MRI.
Time frame: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
- Individual participant dataSharing planned: Yes. IPD collected and stored within the Cardio-Neuro-Mind Data Platform (CNMDP) to which data sharing consent has been provided by the individual participant.
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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.
Jennifer Phillips, PhD principal investigator
University of Ottawa Institute for Mental Health Research at The Royal
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing ketamine hydrochloride in people with Suicidal Ideation and Major Depressive Disorder (MDD), run by The Royal's Institute of Mental Health Research at 1 site in Canada.
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 6 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 19 May 2026. 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 Canada. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Coordinator (613-722-6521 ext. 6934, suzannah.wojcik@theroyal.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in white matter microstructure from pre-treatment to post-treatment, assessed via MRI. (time frame: Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours)). 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 19 May 2026.