iTBS+D-Cycloserine for Youth Suicide

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 both implicit and explicit measures of suicide risk.

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 and both implicit and explicit suicide risk. Implicit suicide risk is measured with a computerized test, called the death/suicide implicit association test (Death/Suicide IAT), and explicit suicide risk is defined as suicidal thoughts reported by the individual.

In the current study, we aim to determine whether the effects of iTBS can be augmented with D-Cycloserine to reduce suicide risk in the EA population. Typical courses of iTBS involve daily treatments over 6 weeks, a timeframe that is not acceptable in individuals experiencing suicidal ideation. For this reason, we will build on data indicating that treatment courses can be condensed by delivering multiple treatments in a single day to accelerate symptomatic improvements. Specifically, our data suggests that (1) 4-weeks of daily iTBS+D-Cycloserine significantly improves implicit and explicit suicide risk and (2) a single-dose of D-Cycloserine paired with two iTBS treatments separated by one hour, enhances the physiological effects of iTBS. As such, in this study, participants will receive two treatments per day, separated by an hour, thereby accelerating a typical 4-week course to 2 weeks.

Research Question and Objectives: To conduct a 2-week double-blind placebo-controlled randomized clinical trial where 54 participants will be randomly assigned to one of two groups: 1) accelerated iTBS+D-Cycloserine, and 2) accelerated iTBS+placebo. The primary outcome of the study is performance on the Death/Suicide-IAT, a measure of suicide risk; however, we will also determine whether pairing stimulation with D-Cycloserine enhances the antidepressant effects of iTBS, reduces suicidal ideation in this population, and reduces the likelihood of engaging in suicidal behavior or having suicidal crises over the following six months.

Conditions

• Suicidal Ideation
• Suicide, Attempted
• Depression, Anxiety

Interventions

DRUG

D-Cycloserine

Participants will orally ingest a capsule containing a 100mg dose of the antibiotic d-cycloserine daily (Monday-Friday) during 2 weeks of twice daily rTMS treatment (20 sessions) 60-120 minutes prior to the first rTMS treatment of the day.

DEVICE

intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation

Repetitive Transcranial magnetic stimulation (rTMS) will be delivered using a MagPro X100 device with B70 coil and the intermittent theta burst (iTBS) protocol to the left dorsolateral prefrontal cortex. Participants will receive twice daily treatments (Monday-Friday) over two weeks (20-sessions).

DRUG

Placebo oral tablet

Participants will orally ingest a capsule identical to that containing the study medication, however, this capsule will contain a placebo. They will ingest this capsule daily (Monday-Friday) for 2 weeks of twice-daily rTMS treatment (20 sessions) 60 - 120 minutes prior to the first rTMS treatment of the day.

Sponsors & Collaborators

• University of Alberta

  collaborator OTHER

• University of Calgary

  lead OTHER

Principal Investigators

• Alexander McGirr, MD PhD · University of Calgary

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

24 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-11

Primary Completion

2026-07-31

Completion

2026-09-30

Countries

• Canada

Study Locations