iTBS+D-Cycloserine for Youth Suicide

Suicidal Ideation Clinical Trial

Official title: A Randomized Placebo-controlled Trial of Adjunctive D-Cycloserine and Accelerated Intermittent Theta Burst Stimulation for Emerging Adults With Suicidal Ideation

Status Recruiting

Clinical Trial Summary

Background and Rationale: Suicide is the second leading cause of death in Canadian Emerging Adults (EAs; 18-24yrs). Current treatments for suicidal thoughts and behaviors are limited and novel treatments are required to save lives. Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulation treatment for major depressive disorder, a mental health condition at high risk for suicide. It is well tolerated and effective. However, in the child and youth population, it does not appear to be superior to sham-TMS. Therefore, strategies for enhancing TMS outcomes are required.

Over time, TMS can change the function of brain regions important in depression to reduce the symptoms of depression, including suicidal ideation. The investigators believe this occurs through a process called 'synaptic plasticity', or the process by which neurons change their connectivity with other neurons in an activity-dependent manner. Using an adjunct to facilitate these changes in the EA population may improve TMS outcomes, including its effect on suicidal ideation.

The investigators' previous data indicates that, in adults, the effects of a TMS protocol called intermittent theta-burst stimulation (iTBS) can be enhanced by pairing stimulation with a medication called D-Cycloserine. This FDA-approved medication leads to enhanced synaptic plasticity with iTBS. In adults, this combination led to greater improvements in depression symptoms, with a notable rapid resolution of suicidal thoughts as well as improvements on a computerized test that is associated with future suicidal behavior.

Research Question and Objectives: To conduct a 2-week double-blind placebo-controlled randomized clinical trial where 60 participants will be randomly assigned to one of two groups: 1) accelerated iTBS+D-Cycloserine, and 2) accelerated iTBS+placebo. Participants will receive a weight-based dose of D-Cycloserine or placebo as an adjunct to iTBS (25mg/17.5kg of body weight).

Clinical Trial Description

Methods: 60 participants between 18-24 years old with suicidal ideation, defined as a score ≥4 on the Depression Symptom Inventory-Suicidality Subscale (DSI-SS), will be recruited. It is important to note that suicidal ideation occurs on a spectrum and that scores on the DSI-SS range from 0-12. A score of 4 on the DSI-SS is considered high enough to warrant additional screening but does not indicate active suicidal ideation, intent, or plan. However, those with active suicidal ideation, intent, or plan will be eligible to participate in the study if they are currently admitted as an inpatient.

Participants will complete a screening visit to determine eligibility based on the inclusion/exclusion criteria. If the participants are not eligible, no further study procedures will be conducted. Eligible subjects will be randomized in a 1:1 ratio to receive either accelerated iTBS+placebo or accelerated iTBS+D-Cycloserine. The randomization sequence will be generated with random number generation, a block size of 10, and allocation concealment, and the investigators will stratify blocks based on whether the participant is a psychiatric inpatient or outpatient.

Double-blind assignment and allocation concealment will be maintained by sequential numbering. Patients will be randomly assigned to receive either accelerated iTBS+D-Cycloserine or accelerated iTBS+placebo treatments. Patients without blood work within the past month will have laboratory tests done to rule out hematological, hepatic, and renal disease.

Clinical outcomes will be quantified using change on the Scale for Suicidal Ideation (SSI) and self-reported measures of depression and anxiety. These symptoms will be assessed at baseline, week-1 (halfway), week-2 (end of treatment), and one month. Suicidal behaviors over a 6-month follow-up period will also be assessed using the Columbia Suicide Severity Rating Scale (CSSRS) and medical records. Cognition will be assessed at baseline and end of treatment (week 2). ;

Related Conditions & MeSH terms

• Depression
• Depression, Anxiety
• Suicidal Ideation
• Suicide
• Suicide, Attempted

• NCT number: NCT06121284
• Study type: Interventional
• Source: University of Calgary
• Contact: Alexander McGirr, MD PhD
• Phone: 403 210 6410
• Email: alexander.mcgirr@ucalgary.ca
• Status: Recruiting
• Phase: Phase 2
• Start date: March 11, 2024
• Completion date: September 2026