iTBS+D-Cycloserine for Youth Suicide

Phase

Condition

Suicide

Depression

Treatment

Placebo oral tablet

D-Cycloserine

intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation

Clinical Study ID

NCT06121284

REB22-1115

Ages 18-24
All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

Individuals aged 18 to 24 years
Any sex or gender
Are competent to consent to treatment
Have previously attempted suicide as defined by the Columbia Suicide Severity RatingScale
Currently have suicidal ideation as defined by a score ≥4 on item 10 of the MADRS inthe past week. Individuals with active suicidal ideation, defined as suicidalideation with the intention to act on a plan that might result in death, are onlyeligible if currently hospitalized
Moderate depression measured on the 17-item Hamilton Rating Scale for Depression (HAMD-17) ≥15
Are able to adhere to the treatment schedule
Pass the TMS adult safety screening (TASS) questionnaire
Have a normal ECG, CBC, electrolytes, BUN, creatinine, eGFR, AST, ALT, and GGTwithin the last month.

Exclusion

Exclusion Criteria:

Allergy to cycloserine or any excipients due to possible anaphylaxis or otherreactions.
Current alcohol or substance misuse.
Current symptoms or history of psychosis, as this can be aggravated byD-Cycloserine.
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 requiresthat women of reproductive potential utilize either highly effective birth controlor double barrier method of contraception. Abstinence is only acceptable when it isthe usual and preferred lifestyle of the participant.
Have failed a course of ECT in the current episode. Previous ECT treatment outsideof the current episode does not influence inclusion.
Have previously failed a course of rTMS treatment
Have any significant neurological disorder or insult as this increased the risk ofadverse events with rTMS including, but not limited to any condition likely to beassociated with increased intracranial pressure, space occupying brain lesion, anyhistory of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea,multiple sclerosis, significant head trauma with loss of consciousness for greaterthan or equal to 15 minutes
Have concomitant major unstable medical illness, cardiac pacemaker or implantedmedication pump
Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlearimplants, 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 movedue to the rapidly alternating magnetic field generated by rTMS.
Are currently being treated with GABA agonists such as benzodiazepines,cyclopyrrolones, gabapentin/pregabalin, or anticonvulsant due to the potential tolimit TMS efficacy
Those with a history of intracranial implants or metal, or with any potential metalfragments in the body (particularly in the orbits).

Study Design

Placebo oral tablet

March 11, 2024

September 30, 2026

Study Description

Methods: 54 participants between 18-24 years old with clinically significant past week suicidal ideation, defined as a score ≥4 on item 10 of the Montgomery Asberg Depression Rating Scale (MADRS), at least moderate depressive symptoms (≥15 Hamilton Depression Rating Scale-17 [HAMD-17]), and a history of at least one suicide attempt will be recruited. It is important to note that suicidal ideation occurs on a spectrum and that scores on the MADRS item 10 range from 0-6. A score of 4 = "Probably better off dead. Suicidal thoughts are common, and suicide is considered as a possible solution, but without specific plans or intention." A score of 6 = "Explicit plans for suicide when there is an opportunity. Active preparations for suicide." Within this range, an individual may have active or passive suicidal ideation with or without intent or a plan. Individuals 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 6, and allocation concealment.

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.

The primary outcome of interest is change in performance on the Death/Suicide-IAT from baseline to treatment end. Performance on this measure and other cognitive tasks will also be assessed at 1-month and 6-month follow-ups.

Clinical outcomes will be quantified using change on the clinician-rated Scale for Suicidal Ideation (SSI) and MADRS and self-reported measures of depression and anxiety. These symptoms will be assessed at baseline, week-1 (halfway), week-2 (end of treatment), one month, and 6-months post-treatment. Change in suicidal behaviors over the 6-months prior and following treatment will also be assessed using the Columbia Suicide Severity Rating Scale (CSSRS) and medical record review.

Connect with a study center

University of Calgary
Calgary, Alberta T2N 1N4
Canada
Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.