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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand brain activity when individuals think about or attempt suicide. It gathers information through brain imaging, questionnaires, and other tests to explore how the drug ketamine (also known as Ketalar or Special K) might help. Participants include those who are currently or have been suicidal, those with depression or anxiety who haven't been suicidal, and healthy volunteers. Individuals who have recently thought about or attempted suicide and are willing to be hospitalized might be suitable for this trial. As a Phase 2 trial, this research measures ketamine's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ketamine can quickly reduce suicidal thoughts in people with depression. One study found that ketamine is safe in the short term and can help those with severe suicidal thoughts. However, some studies suggest a risk of increased suicidal behavior shortly after taking ketamine, particularly in young people aged 10-24. Prospective participants should consider these findings when thinking about joining a trial involving ketamine. Discussing any concerns with a healthcare provider can provide guidance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for suicide risk, which often include antidepressants and talk therapy, ketamine hydrochloride infusion works by rapidly targeting the brain's NMDA receptors. Researchers are excited about ketamine because it can potentially reduce suicidal thoughts within hours, compared to the weeks it might take for traditional antidepressants to show effects. This fast-acting nature, combined with a unique mechanism of action, offers a promising alternative for individuals at immediate risk of suicide.

What evidence suggests that ketamine might be an effective treatment for suicide risk?

Research has shown that ketamine, administered in this trial as a Ketamine Hydrochloride infusion, can quickly reduce suicidal thoughts in people with depression. Studies have found that a single ketamine treatment can lower these thoughts within 24 hours for more than half of the recipients. One study found ketamine particularly helpful for individuals with severe depression and suicidal thoughts. This fast-acting treatment is crucial for those at risk of suicide. Overall, ketamine holds significant promise in reducing the risk of suicide in individuals struggling with depression. ^{2 6 7 8 9}

Who Is on the Research Team?

Carlos A Zarate, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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