Understanding and Treating Suicidal Ideation With Ketamine: A Diffusion Magnetic Resonance Imaging Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Change in white matter microstructure from pre-treatment to post-treatment, assessed via MRI.
Study Overview
Brief 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 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
- •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
Arms & Interventions
Ketamine
Participants will undergo a total of four IV ketamine infusions (0.5 mg/kg infused over 40 minutes), administered twice weekly for two weeks.
Intervention: ketamine hydrochloride (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Change in extracellular free water from pre-treatment to post-treatment, assessed via MRI.(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.(Pre-treatment (up to -48 hours) to post-treatment (24+/-6 hours))
Investigators
Jennifer Phillips
Interim Scientific Director and Scientist
The Royal's Institute of Mental Health Research