iTBS + D-Cycloserine for Suicidal Thoughts

Overseen By Alexander McGirr, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must be taking: D-Cycloserine

Must not be taking: GABA agonists

Disqualifiers: Psychosis, Pregnancy, Neurological disorders, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 23

Duration: 2 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether combining a brain stimulation treatment called iTBS with the medication D-Cycloserine (an antibiotic that may affect the brain) can reduce suicidal thoughts in young adults. The focus is on individuals who have previously attempted suicide and currently experience frequent suicidal thoughts. Participants will be divided into two groups: one will receive iTBS with D-Cycloserine, and the other will receive iTBS with a placebo. The goal is to determine if this combination can quickly and effectively lower suicide risk and improve depression symptoms. Young adults with moderate depression and recent suicidal thoughts may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically GABA agonists like benzodiazepines, gabapentin, or anticonvulsants, as they might affect the treatment's effectiveness.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using iTBS (a type of brain stimulation) with D-Cycloserine (a medication) may help reduce suicidal thoughts in people with depression. Studies have found that this combination lowers suicidal thoughts more quickly and effectively than iTBS with a placebo.

The FDA has already approved D-Cycloserine for other uses, indicating it is likely well-tolerated. However, like any treatment, side effects may occur. Current evidence suggests this combination is generally safe, but more research is needed to fully understand its safety in young adults with suicidal thoughts. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for suicidal thoughts?

Researchers are excited about iTBS combined with D-Cycloserine for treating suicidal thoughts because it offers a new approach compared to traditional interventions like antidepressants and psychotherapy. Most treatments for suicidal thoughts can take weeks to show effectiveness, but this combination has the potential to deliver faster results. D-Cycloserine, originally used as an antibiotic, is being repurposed to enhance the effects of brain stimulation therapy (iTBS), which targets specific brain areas more rapidly. This innovative pairing could significantly shorten the time required to reduce suicidal thoughts, providing a crucial lifeline for those in need.

What evidence suggests that iTBS+D-Cycloserine might be an effective treatment for suicidal thoughts?

Research shows that using intermittent theta-burst stimulation (iTBS) with D-Cycloserine may help reduce suicidal thoughts in people with depression. In this trial, participants will receive either D-Cycloserine or a placebo alongside iTBS. Studies have found that combining iTBS and D-Cycloserine can improve depression symptoms and lower suicidal thoughts. D-Cycloserine enhances brain cell connectivity and communication, potentially boosting the effects of iTBS. This approach has shown quicker results in reducing both suicidal thoughts and depression, offering hope for those struggling with these issues. While more research is needed, early evidence suggests this combination could be very helpful for people at risk. ^{1 2 3 6 7}

Who Is on the Research Team?

Alexander McGirr, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for young adults aged 18-24 with moderate depression and suicidal thoughts or a history of suicide attempts. They must be able to consent, pass safety screenings including an ECG and blood tests, and commit to the treatment schedule. Hospitalized individuals with active suicidal plans can also join.

Inclusion Criteria

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

Are able to adhere to the treatment schedule

Pass the TMS adult safety screening (TASS) questionnaire

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive accelerated iTBS+D-Cycloserine or iTBS+placebo treatments, with two sessions per day over 2 weeks

2 weeks

20 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1-month and 6-months post-treatment

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• iTBS+D-Cycloserine

Trial Overview The study is testing whether D-Cycloserine medication enhances the effects of iTBS (a type of brain stimulation therapy) in reducing depressive symptoms and suicidal thoughts over two weeks. Participants will either receive iTBS+D-Cycloserine or iTBS+placebo randomly.

How Is the Trial Designed?

Group I: D-Cycloserine Experimental Treatment 2 Interventions

Participants will orally ingest a standard 100mg dose of D-Cycloserine daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). D-Cycloserine will be ingested 60-120 minutes prior to the first rTMS treatment of the day.

Group II: Placebo Placebo Group 2 Interventions

Participants will orally ingest a standard 100mg dose of a microcrystalline placebo capsule daily (Monday-Friday) during 2 weeks of accelerated rTMS treatments (20 sessions; 2 sessions/day separated by 1 hour). The Placebo will be ingested 60-120 minutes prior to the first rTMS treatment of the day.

iTBS+D-Cycloserine is already approved in United States, Canada for the following indications:

Approved in United States as D-Cycloserine for:

• Tuberculosis

Approved in United States as Seromycin for:

• Tuberculosis

Approved in Canada as D-Cycloserine for:

• Tuberculosis

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

University of Alberta

Collaborator

Trials

957

Recruited

437,000+

Published Research Related to This Trial

Intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex significantly reduced suicidal ideation and depressive symptoms in adolescents with major depressive disorder over a 2-week treatment period involving 10 sessions.

The study involved 45 participants, and those with higher initial depression and suicidal ideation scores experienced greater improvements, suggesting that iTBS is particularly effective for more severely affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent theta burst stimulation on suicidal ideation and depressive symptoms in adolescent depression with suicide attempt: A randomized sham-controlled study. Zhao, Y., He, Z., Luo, W., et al.[2023]

In a study involving 81 participants with major depressive disorder, accelerated intermittent theta burst stimulation (iTBS) significantly reduced suicidality and depressive symptoms over a 6-week period, indicating its potential as an effective treatment.

The intervention was found to be safe, with no serious adverse events reported, and showed particularly pronounced anti-suicidal effects in individuals with higher risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidality and relief of depressive symptoms with intermittent theta burst stimulation in a sham-controlled randomized clinical trial. Wilkening, J., Witteler, F., Goya-Maldonado, R.[2023]

Accelerated intermittent Theta Burst Stimulation (iTBS) was found to be safe and well tolerated in a study of 50 treatment-resistant depressed patients, with no worsening of suicidal ideation observed during the treatment.

The study showed a significant decrease in suicide risk, as measured by the Beck Scale of Suicide Ideation, lasting up to one month after treatment, regardless of whether patients received active or sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. Desmyter, S., Duprat, R., Baeken, C., et al.[2020]

In a study of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

Accelerated intermittent theta burst stimulation (TBS) was found to be safe and well tolerated in 12 suicidal therapy-resistant depressed patients, showing a significant decrease in suicidal ideation over time.

However, the reduction in suicidal thoughts was not definitively linked to the active TBS treatment compared to sham stimulation, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Desmyter, S., Duprat, R., Baeken, C., et al.[2022]

In a study involving 45 patients with major depressive disorder, both active and placebo intermittent theta burst stimulation (aiTBS) led to rapid decreases in suicidal thoughts, indicating a potential for quick intervention.

The reduction in suicidal ideation after placebo aiTBS was linked to significant decreases in brain perfusion in the frontopolar prefrontal cortex, suggesting that even placebo treatments can influence brain activity related to cognitive processes and suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo aiTBS attenuates suicidal ideation and frontopolar cortical perfusion in major depression. Baeken, C., Wu, GR., van Heeringen, K.[2020]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39905763/

Intermittent theta-burst stimulation with adjunctive D ... Conclusions: Adjunctive D-cycloserine with iTBS is a promising strategy to reduce suicidal ideation and implicit suicide risk in depression.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06121284

NCT06121284 | iTBS+D-Cycloserine for Youth Suicide A Randomized Placebo-controlled Trial of Adjunctive D-Cycloserine and Accelerated Intermittent Theta Burst Stimulation for Emerging Adults With Suicidal ...

3. researchgate.net researchgate.net/publication/388716878_Intermittent_theta-burst_stimulation_with_adjunctive_D-cycloserine_rapidly_resolves_suicidal_ideation_and_decreases_implicit_association_with_deathsuicide

(PDF) Intermittent theta-burst stimulation with adjunctive D- ... Conclusions Adjunctive D-cycloserine with iTBS is a promising strategy to reduce suicidal ideation and implicit suicide risk in depression.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11968122/

Intermittent theta-burst stimulation with adjunctive D- ... Adjunctive D-cycloserine with iTBS is a promising strategy to reduce suicidal ideation and implicit suicide risk in depression.

5. researchgate.net researchgate.net/publication/364372620_Efficacy_of_Adjunctive_D-Cycloserine_to_Intermittent_Theta-Burst_Stimulation_for_Major_Depressive_Disorder_A_Randomized_Clinical_Trial

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta- ... Findings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06121284/itbsd-cycloserine-for-youth-suicide

iTBS+D-Cycloserine for Youth Suicide D-Cycloserine. intermittent Theta-Burst-repetitive Transcranial Magnetic Stimulation ... augmented with D-Cycloserine to reduce suicide risk ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36223114/

Efficacy of Adjunctive D-Cycloserine to Intermittent Theta- ... Findings from this clinical trial indicate that adjunctive D-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment ...