iTBS+D-Cycloserine for Youth Suicide

• Status: Not yet recruiting
• Trial end date: 2026-09-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Calgary
• Collaborator: University of Alberta
• Treatments: Cycloserine

Criteria

Inclusion Criteria:

1. Individuals aged 18 to 24 years

2. Any sex or gender

3. Are competent to consent to treatment

4. Have previously attempted suicide as defined by the Columbia Suicide Severity Rating Scale

5. Currently have suicidal ideation as defined by a score ≥4 on the DSI-SS. For individuals with active suicidal ideation, defined as suicidal ideation with the intention to act on a plan that might result in death, are only eligible if currently hospitalized

6. Moderate depression measured on the 17-item Hamilton Rating Scale for Depression (HAMD-17) ≥15

7. Are able to adhere to the treatment schedule

8. Pass the TMS adult safety screening (TASS) questionnaire

9. Have a normal ECG, CBC, electrolytes, BUN, creatinine, eGFR, AST, ALT, and GGT within the last month.

Exclusion Criteria:

1. Allergy to cycloserine or any excipients due to possible anaphylaxis or other reactions.

2. Current alcohol or substance misuse.

3. Current symptoms or history of psychosis, as this can be aggravated by D-Cycloserine.

4. Are currently pregnant, breast feeding or plan to become pregnant during the study, as the effects of D-Cycloserine on the fetus are unknown. Health Canada requires that women of reproductive potential utilize either highly effective birth control or double barrier method of contraception. Abstinence is only acceptable when it is the usual and preferred lifestyle of the participant.

5. Have failed a course of ECT in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.

6. Have previously failed a course of rTMS treatment

7. Have any significant neurological disorder or insult as this increased the risk of adverse events with rTMS including, but not limited to any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 15 minutes

8. Have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump

9. Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed because these can heat or move due to the rapidly alternating magnetic field generated by rTMS.

10. Are currently being treated with GABA agonists such as benzodiazepines, cyclopyrrolones, gabapentin/pregabalin, or anticonvulsant due to the potential to limit TMS efficacy

11. Those with a history of intracranial implants or metal, or with any potential metal fragments in the body (particularly in the orbits).