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

81 Participants Needed

Trial Summary

What is the purpose of this trial?

Obsessive Compulsive Disorder (OCD)is a common and debilitating illness. For an unacceptable proportion of patients, depressive symptoms remain impairing despite multiple treatments. In August 2018, the FDA approved transcranial magnetic stimulation (TMS) for the treatment of OCD based on a large study demonstrating efficacy. Our neurophysiological data and clinical data in depression suggests that we can enhance the effects of TMS by using an adjunctive medication called D-Cyloserine (DCS, 100mg) in conjunction with stimulation. The mechanism by which this is achieved is called synaptic plasticity, or the activity dependent changes that occur with brain stimulation. Research Question and Objectives: To conduct a randomized sham- and placebo-controlled trial of DCS in adjunct with rTMS in OCD. Participants will be randomized to receive 100mg of DCS or placebo together with TMS.

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.

What data supports the effectiveness of the treatment D-Cycloserine + TMS for Obsessive-Compulsive Disorder?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) can improve symptoms and reduce illness severity in patients with OCD, suggesting potential benefits when combined with other treatments like D-Cycloserine. ^{1 2 3 4 5}

Is D-Cycloserine safe for use in humans?

D-Cycloserine, when used in low doses, is generally considered safe for humans. It has been studied in various psychiatric and neurological conditions, and while it shows potential benefits, its safety in low-dose therapy is supported by research. ^{6 7 8 9 10}

How is the treatment D-Cycloserine + TMS for OCD different from other treatments?

This treatment combines D-Cycloserine, a drug that may enhance learning, with iTBS repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive method that uses magnetic fields to stimulate specific brain areas. This combination aims to improve the effectiveness of rTMS by potentially enhancing the brain's response to the magnetic stimulation, offering a novel approach compared to traditional medication or therapy alone. ^{1 2 11 12 13}

Research Team

Alexander McGirr, MD

Principal Investigator

University of Calgary

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) improves symptoms and reduces clinical illness in patients suffering from OCD--Results from a single-blind, randomized clinical trial with sham cross-over condition. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Comparing the effectiveness of CBT and low-frequency rTMS in reducing symptom severity and depression and improving working memory in adults with OCD: a clinical trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Difficult-to-treat pediatric obsessive-compulsive disorder: feasibility and preliminary results of a randomized pilot trial of D-cycloserine-augmented behavior therapy. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

D-cycloserine augmentation of behavior therapy for anxiety and obsessive-compulsive disorders: A meta-analysis. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. [2021]

9. England pubmed.ncbi.nlm.nih.gov

D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: current perspectives. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of obsessive-compulsive disorder. [2020]

13. United States 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. [2023]