NCT06121284

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

Recruiting now Phase 2 Last updated 8 November 2024

What this trial tests

Phase 2 trial testing D-Cycloserine in Suicidal Ideation in 54 participants. Currently enrolling.

Timeline

11 March 2024

Primary endpoint
1 July 2026

1 September 2026

Quick facts

Lead sponsor	University of Calgary
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	54
Start date	11 March 2024
Primary completion	1 July 2026
Estimated completion	1 September 2026
Sites	1 location across Canada

Drugs / interventions tested

• D-Cycloserine — full drug profile →
• intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation
• Placebo oral tablet — full drug profile →

Conditions studied

• Suicidal Ideation — all drugs for Suicidal Ideation →
• Suicide, Attempted — all drugs for Suicide, Attempted →
• Depression, Anxiety — all drugs for Depression, Anxiety →

Sponsor

University of Calgary

Who can join

Adults 18 to 24, any sex, with Suicidal Ideation or Suicide, Attempted. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Performance on the Death Implicit Association Test (D-IAT) at treatment end
  Time frame: Change from baseline to end of treatment (week 2)
  The D-IAT measures reaction time in categorizing life and death-related words. Different pairings of target attributes (Life/Death) and attribute dimensions (Me/Not Me) create implicit associations between the self with life and death. The D-IAT score is interpreted as a difference in strength of implicit association of the self with life and death. Scores range from -2 (strong implicit associatio

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Emerging Medications for Treatment-Resistant Depression: A Review with Perspective on Mechanisms and Challenges.
   Lucido MJ, Dunlop BW. · · 2025 · cited 7× · PMID 40002494 · DOI 10.3390/brainsci15020161