Brain Imaging + Ketamine for Suicide Risk

Recruiting at 1 trial location

Overseen By Carlos A Zarate, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Reversible MAOIs, others

Disqualifiers: Psychotic features, Drug dependence, Serious medical conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

325 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: There are no good treatments for people considering suicide. Researchers want to study suicide with questions, blood tests, brain imaging, and sleep studies. They hope to better understand suicide, so they can help suicidal people. Objective: To understand what happens in the brain when someone has thought about or attempted suicide. Eligibility: Group 1: Adults ages 18 70 who have thought about or attempted suicide recently Group 2: Adults ages 18 70 who have thought about or attempted suicide in the past Group 3: Adults ages 18 70 who have depression or anxiety, but have never thought about suicide Group 4: Healthy volunteers the same ages. Design: Participants will be screened in another protocol. Adults who have recently thought about or attempted suicide must be referred by a doctor. They may do up to 3 phases of this study. Groups 2, 3 and 4 will do only Phase 1 and will not get ketamine. Phase 1: 1 week in hospital. Participants will have: Physical exam. Questions about thoughts and feelings. Thinking and memory tests and simple tasks. Blood and urine tests. Two MRI scans. Participants will lie on a table that slides into a metal cylinder that takes pictures. They will have a coil over their head and earplugs and do a computer task. Sleep test. Disks and bands will be placed on the body to monitor it during sleep. Magnetic detectors on their head while they perform tasks. A wrist monitor for activity and sleep. Lumbar puncture (optional). A needle will collect fluid from the back. Shock experiments (optional). Participants will observe pictures and sounds and feel a small shock on the hand. Phase 2: 4 days in hospital. A thin plastic tube will be placed in each arm, one for blood draws, the other to get the drug ketamine once. Participants will repeat most of the Phase 1 tests. Phase 3: up to 4 more ketamine doses over 2 weeks. Participants will have follow-up calls or visits at 6 months and then maybe yearly for 5 years. ...

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. Specifically, you must not have taken a reversible MAOI (a type of antidepressant) within 2 weeks before Phase II or III, and any other disallowed medications must be stopped within a period based on their half-lives (time it takes for the drug's active substance to reduce by half in the body) before these phases.

What data supports the effectiveness of the drug Ketalar (ketamine) for reducing suicide risk?

Research shows that ketamine can quickly reduce suicidal thoughts in people with depression, often within 24 to 72 hours after treatment. It works by affecting brain chemicals and structures, which may help improve mood and reduce the desire to harm oneself. ^{1 2 3 4 5}

Is ketamine safe for use in humans, particularly for reducing suicide risk?

Research shows that ketamine, when used in controlled medical settings, can rapidly reduce suicidal thoughts and is generally considered safe for short-term use. Studies have reported significant decreases in suicidality and depression with ketamine treatment, and it has been used safely in both infusion and oral forms in clinical trials. ^{1 3 4 6 7}

How does the drug ketamine differ from other treatments for suicide risk?

Ketamine is unique because it works rapidly to reduce suicidal thoughts by affecting brain chemistry, specifically through its action on NMDA receptors, which are involved in glutamate transmission. Unlike traditional antidepressants that may take weeks to show effects, ketamine can quickly enhance brain plasticity and increase grey matter volume, offering a novel approach for those at high risk of suicide. ^{1 2 3 4 7}

Research Team

Carlos A Zarate, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Eligibility Criteria

This trial is for adults aged 18-70 who have recently considered or attempted suicide, those with past suicidal thoughts or attempts, individuals with depression or anxiety but no suicidal ideation, and healthy volunteers. Participants must understand the study well enough to consent and agree to use effective birth control if they can get pregnant.

Inclusion Criteria

Phase I: Group 4 (Healthy Volunteers) - A level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document

Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators) - Participants must verify understanding of the protocol by a score greater than or equal to 80% on the Ketamine Response consent quiz

Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators) - MADRS score of over 10, HAMA score of over 7, or SSI score of 2 or more

Exclusion Criteria

Phase I: Group 4 (Healthy Volunteers) - Current or past Axis I diagnosis

Phase I: Groups 1-3 and 5 (Patients) - Current psychotic features or cognitive impairment that would preclude understanding of the consenting process or tests/examinations

Phase I: Group 4 (Healthy Volunteers) - Current or past alcohol or substance abuse or dependence diagnosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Baseline

Participants undergo multimodal assessment including blood draw, lumbar puncture, neuroimaging, polysomnography, clinical ratings, and experimental paradigms.

1 week

In-hospital stay

Ketamine Response

Participants receive a single open-label trial of ketamine to identify potential biomarkers of antisuicidal response.

4 days

In-hospital stay

Repeated Ketamine Infusions

Participants receive up to 4 additional ketamine doses over 2 weeks.

2 weeks

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up evaluations at six months and possibly yearly for 5 years.

6 months to 5 years

Treatment Details

Interventions

• Neurobiology of Suicide

Trial Overview The study aims to understand brain activity related to suicide through interviews, tests, MRI scans using different strength scanners (3T and 7T), sleep studies, blood tests, and optional tasks like a lumbar puncture. Some participants may receive ketamine infusions in later phases of the trial.

Participant Groups

Group I: 1 Experimental Treatment 5 Interventions

Ketamine Hydrochloride infusion

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Findings from Research

A 6-week treatment with low-dose oral ketamine significantly increased grey matter in key brain regions associated with mood regulation, such as the nucleus accumbens and thalamus, in adults experiencing chronic suicidality.

These findings suggest that ketamine may promote neurogenesis and enhance synaptic plasticity, potentially offering a rapid therapeutic effect for individuals at risk of suicide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-week oral ketamine treatment for chronic suicidality is associated with increased grey matter volume. Gallay, CC., Forsyth, G., Can, AT., et al.[2022]

Ketamine has emerged as a promising treatment for major depressive disorder, especially for patients who are resistant to other therapies, showing rapid reductions in depressive symptoms and suicidal thoughts at subanesthetic doses.

Research indicates that ketamine may promote neuroplasticity in brain networks associated with depression, although the exact mechanisms of its antidepressant effects are still not fully understood, as evidenced by a review of 51 studies using various neuroimaging techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine. Zavaliangos-Petropulu, A., Al-Sharif, NB., Taraku, B., et al.[2023]

Ketamine, when administered at subanaesthetic doses, has shown rapid antidepressant effects and significant suppression of suicidal thoughts in depressed patients, highlighting its potential as a treatment for suicidal ideation.

The review emphasizes the need for further neuroimaging studies to explore how ketamine affects specific brain regions in suicidal patients, which could enhance our understanding of its mechanisms and improve treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and suicidal ideation in depression: Jumping the gun? Rajkumar, R., Fam, J., Yeo, EY., et al.[2015]

In a study of 10 patients with major depressive disorder, those who responded to ketamine treatment showed higher fractional anisotropy (FA) in specific brain regions compared to non-responders, suggesting that white matter microstructure may influence treatment outcomes.

Non-responders exhibited distinct changes in white matter metrics, such as decreased FA and increased radial diffusivity (RD) in certain pathways, indicating that structural differences in the brain could potentially predict who will benefit from ketamine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural connectivity and response to ketamine therapy in major depression: A preliminary study. Vasavada, MM., Leaver, AM., Espinoza, RT., et al.[2018]

Ketamine has shown significant and rapid efficacy in reducing suicidal ideation in depressed patients, with effects observable within the first 72 hours after administration.

The mechanisms behind ketamine's effectiveness include reducing anhedonia, activating neuroplasticity, lowering inflammation, and involving the opioidergic system, although its long-term impact on preventing suicidal behaviors remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How can ketamine be used to manage suicidal risk?] Olié, E., Lengvenyte, A., Courtet, P.[2023]

In a study involving 16 recent suicide attempters, a single intravenous dose of ketamine (0.5 mg/kg) led to rapid and significant reductions in suicidal thoughts within 24 hours, with effects lasting up to 6 months post-infusion.

The results indicate that ketamine is a safe and effective treatment for reducing suicidality in high-risk patients, suggesting it could be integrated into existing healthcare settings for those in acute psychiatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. Shivanekar, S., Gopalan, P., Pizon, A., et al.[2023]

In a study of 28 participants with chronic suicidality and major depressive disorder, oral ketamine treatment led to increased hippocampal grey matter volumes in responders compared to non-responders after 6 weeks, suggesting its potential to promote neuroplasticity.

The findings indicate that larger hippocampal volumes, particularly in the left hemisphere, may serve as predictive biomarkers for individuals who are likely to respond positively to ketamine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal subfield volumes predict treatment response to oral ketamine in people with suicidality. Dutton, M., Boyes, A., Can, AT., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Six-week oral ketamine treatment for chronic suicidality is associated with increased grey matter volume. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Neuroimaging-Derived Biomarkers of the Antidepressant Effects of Ketamine. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Ketamine and suicidal ideation in depression: Jumping the gun? [2015]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Structural connectivity and response to ketamine therapy in major depression: A preliminary study. [2018]

5. France pubmed.ncbi.nlm.nih.gov

[How can ketamine be used to manage suicidal risk?] [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A Pilot Study of Ketamine Infusion after Suicide Attempt: New Frontiers in Treating Acute Suicidality in a Real-World Medical Setting. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Hippocampal subfield volumes predict treatment response to oral ketamine in people with suicidality. [2023]