D-Cycloserine + TMS for Obsessive-Compulsive Disorder

Overseen By Alexander McGirr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: Benzodiazepines

Disqualifiers: Psychosis, Neurological disorders, Substance use, 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

Compensation: Varies

Number of Visits: 22

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining the medication D-Cycloserine (DCS) with transcranial magnetic stimulation (TMS) can improve symptoms of obsessive-compulsive disorder (OCD). TMS is already used for OCD, but the trial seeks to assess whether adding DCS enhances its effectiveness. Participants will receive either TMS with DCS, TMS with a placebo, or a sham (fake) TMS with either DCS or a placebo. Individuals with OCD who have not improved after at least two months of standard treatments, such as certain medications or therapy, might be suitable for this trial. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potentially more effective OCD treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must not have changed your dose or started any new psychotropic medications in the 8 weeks before joining. Also, you cannot be taking lorazepam or any other benzodiazepine in the last 4 weeks before the study.

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

Studies have shown that transcranial magnetic stimulation (TMS) is a safe and effective treatment for obsessive-compulsive disorder (OCD). The FDA approved TMS for OCD in 2018 after a large study showed positive results, indicating that TMS is generally well-tolerated and safe. Research on D-cycloserine (DCS) indicates it can safely enhance exposure therapy for anxiety disorders. In these studies, patients did not report significant side effects when taking low doses of DCS, suggesting it is likely safe to use with TMS.

Overall, both TMS and DCS have been studied extensively, suggesting they are safe, especially under medical supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Obsessive-Compulsive Disorder (OCD) because they combine a unique approach to brain stimulation with a potential enhancement from medication. Unlike traditional OCD treatments like SSRIs (Selective Serotonin Reuptake Inhibitors) or CBT (Cognitive Behavioral Therapy), this treatment uses repetitive Transcranial Magnetic Stimulation (rTMS) to target the brain's left medial prefrontal cortex with magnetic pulses. Additionally, some participants receive D-Cycloserine (DCS), an antibiotic that might boost the effects of rTMS by acting on the brain's learning and memory pathways. This combination could potentially accelerate and enhance treatment effectiveness, offering new hope for those who haven't responded to standard therapies.

What evidence suggests that this trial's treatments could be effective for OCD?

Research has shown that transcranial magnetic stimulation (TMS) can help reduce symptoms of obsessive-compulsive disorder (OCD). In studies, TMS proved more effective than a placebo in improving OCD symptoms. The Yale Brown Obsessive Compulsive Scale, a common tool for measuring OCD, indicated improvement with TMS treatment. In this trial, some participants will receive TMS combined with D-cycloserine (DCS), while others will receive TMS with a placebo.

The antibiotic D-cycloserine (DCS) has shown mixed results. Some studies suggest it can enhance therapy effects for anxiety disorders, but other research found no added benefit for OCD treatment. This trial will also include arms where participants receive sham TMS combined with either DCS or a placebo. Combining DCS with TMS might help improve brain changes that reduce OCD symptoms, but further research is needed to confirm this. ^{1 6 7 8 9}

Who Is on the Research Team?

Alexander McGirr, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

Adults aged 18-65 with a confirmed diagnosis of Obsessive Compulsive Disorder (OCD) who haven't responded to certain treatments and have a score ≥ 20 on the YBOCS. Participants must not have changed psychotropic medications in the last 8 weeks, be able to consent, adhere to treatment schedules, and pass TMS safety screenings. Exclusions include allergy to cycloserine, recent substance abuse, suicidal ideation, psychosis history, pregnancy or breastfeeding women, unstable medical conditions or metal implants near the head.

Inclusion Criteria

I tried an antidepressant or therapy for 2 months without improvement or couldn't tolerate the medication.

I understand and can agree to my treatment plan.

Have a score ≥ 20 on the YBOCS

Exclusion Criteria

History of psychosis

I do not have major brain or nerve conditions like epilepsy, Parkinson's, or severe head injuries.

Have an alcohol or substance use disorder within the last 3 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive daily rTMS treatment with either DCS or placebo for 4 weeks

4 weeks

20 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Open-label extension (optional)

Participants who received sham-rTMS are offered an additional 4 weeks of open-label rTMS

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• D-cycloserine
• iTBS repetitive Transcranial Magnetic Stimulation (rTMS)
• Placebo oral capsule
• Sham rTMS

Trial Overview The trial is testing if D-cycloserine (DCS), when taken with repetitive Transcranial Magnetic Stimulation (rTMS), can improve OCD symptoms compared to placebo. It's randomized: participants will either get real rTMS with DCS or sham rTMS with a placebo capsule without knowing which one they're getting.

How Is the Trial Designed?

Group I: TMS+DCS Active Control 2 Interventions

The Transcranial Magnetic Stimulation (TMS) involves magnetic stimulation of the brain to the left medial prefrontal cortex (mPFC) daily for four weeks. The stimulation is intermittent Theta-Burst (iTBS). Participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine (DCS) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Group II: TMS+Placebo Active Control 2 Interventions

The Transcranial Magnetic Stimulation (TMS) involves magnetic stimulation of the brain to the left medial prefrontal cortex (mPFC) daily for four weeks. The stimulation is intermittent Theta-Burst (iTBS). 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 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Group III: shamTMS+DCS Placebo Group 2 Interventions

Sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered to the brain. Participants will orally ingest a capsule containing 100mg of the antibiotic d-cycloserine (DCS) daily (Monday-Friday) for 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Group IV: shamTMS+placebo Placebo Group 2 Interventions

Sham rTMS treatment involves scalp stimulation with no magnetic pulse daily for four weeks (20 sessions). Sham rTMS involves only the click replicating the sound of the magnetic discharge, without any magnetic pulse being delivered to the brain. 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 4 weeks of rTMS treatment (20 sessions) one hour prior to rTMS treatment.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) and its advanced form, deep transcranial magnetic stimulation (dTMS), are promising noninvasive treatments for obsessive-compulsive disorder (OCD), targeting specific brain areas to alleviate symptoms.

dTMS, which stimulates deeper brain structures than rTMS, represents a novel approach that may enhance treatment efficacy compared to traditional methods like medication and therapy, although the exact neurobiological mechanisms are still being studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: current perspectives. Lusicic, A., Schruers, KR., Pallanti, S., et al.[2020]

In a study involving 61 treatment-refractory OCD patients, all three rTMS protocols combined with exposure and response prevention (ERP) led to significant reductions in OCD symptoms, with a response rate of 57.4%.

Both high-frequency rTMS to the left dorsolateral prefrontal cortex and the left pre-supplementary motor area resulted in decreased activation in brain areas related to planning and error processing, which correlated with symptom improvement, although no significant differences in symptom reduction were found between the different rTMS groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TMS-induced plasticity improving cognitive control in OCD I: Clinical and neuroimaging outcomes from a randomised trial of rTMS for OCD. Fitzsimmons, SMDD., Postma, T., van Campen, AD., et al.[2023]

In a double-blind study involving 18 subjects with treatment-resistant OCD, repetitive transcranial magnetic stimulation (rTMS) did not show significant efficacy compared to sham treatment after 10 sessions.

After extending to 20 sessions, rTMS resulted in a significant reduction in OCD symptoms, but this effect was not maintained when accounting for depression, indicating limited effectiveness for OCD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation. Sachdev, PS., Loo, CK., Mitchell, PB., et al.[2007]

In a study involving 18 sessions of repetitive transcranial magnetic stimulation (rTMS) on patients with obsessive-compulsive disorder (OCD), no significant improvements were observed in OCD symptoms compared to a sham treatment group.

Both the real rTMS and sham conditions showed similar outcomes, indicating that low-frequency rTMS of the right prefrontal cortex may not be an effective treatment for OCD, suggesting the need for further research to explore optimal stimulation parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study. Alonso, P., Pujol, J., Cardoner, N., et al.[2006]

Active repetitive transcranial magnetic stimulation (rTMS) significantly reduces OCD symptoms, with a moderate effect size based on a meta-analysis of 31 trials.

rTMS targeting various brain areas, including the pre-SMA, DLPFC, ACC/mPFC, and OFC, is shown to be a safe and effective treatment for OCD, although further research is needed to tailor protocols for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Will Transcranial Magnetic Stimulation Improve the Treatment of Obsessive-Compulsive Disorder? A Systematic Review and Meta-Analysis of Current Targets and Clinical Evidence. Grassi, G., Moradei, C., Cecchelli, C.[2023]

A systematic review of three randomized controlled trials on transcranial magnetic stimulation (TMS) for obsessive-compulsive disorder (OCD) found no significant difference in efficacy between active rTMS and sham TMS, based on standardized rating scales.

Due to insufficient data and variability in the trials, the review concluded that there is currently no strong evidence to support the use of TMS as an effective treatment for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder. Martin, JL., Barbanoj, MJ., Pérez, V., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35084071/

Efficacy of D-cycloserine augmented brief intensive ... Conclusions: DCS augmented intensive exposure therapy did not result in overall additional benefits relative to placebo. Intensive exposure ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2769240

Effect of D-Cycloserine on Concentrated Exposure and ... In this study, concentrated exposure and response prevention treatment was effective for patients with difficult-to-treat obsessive-compulsive disorder.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00182000

Study Details | Effectiveness of D-Cycloserine as an Aid to ... This study will assess the effectiveness of Seromycin (D-cycloserine) in enhancing the positive effects of behavior therapy for people with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3034091/

A Preliminary Study of D-Cycloserine Augmentation ... Preliminary results have supported the use of DCS to augment exposure therapy in adult anxiety disorders; however, no data have been reported in any childhood ...

5. iocdf.org iocdf.org/recipients/d-cycloserine-augmentation-of-exposure-and-response-prevention-treatment-for-obsessive-compulsive-disorder/

D-Cycloserine augmentation of exposure and response ... The results showed that for pediatric OCD, D-cycloserine was not better than placebo in increasing CBT's effectiveness (Storch et al., 2007).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00257361

D-Cycloserine Augmentation of Exposure and Response ... Also called a data safety and monitoring ... D-Cycloserine Augmentation of Exposure and Response Prevention Treatment for Obsessive-Compulsive Disorder.

7. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20240181

Intermittent Theta Burst Stimulation With Adjunctive D- ... Here, we present randomized placebo- and sham-controlled trial data testing iTBS with low-dose adjunctive d-cycloserine in OCD, with the ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322307011055

A Randomized Controlled Trial of D-Cycloserine ... The aim of this study was to determine whether 50 mg of DCS enhances ET for social anxiety disorder (SAD) according to a comprehensive set of symptom and life ...

9. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2529151

Efficacy of Augmentation of Cognitive Behavior Therapy ... This randomized clinical trial examines the relative efficacy of weight-adjusted d-cycloserine (25 or 50 mg) vs placebo augmentation of ...