Accelerated Theta-Burst Stimulation for Obsessive-Compulsive Disorder

Overseen By Nick Bassano, MSW

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Serotonin reuptake inhibitors

Disqualifiers: Psychosis, Bipolar, Severe depression, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with Obsessive Compulsive Disorder (OCD) who haven't responded to standard treatments. It uses Transcranial Magnetic Stimulation (TMS), a device that sends magnetic pulses to specific brain areas involved in OCD. Participants will receive stimulation to either the dorsomedial prefrontal cortex (DMPFC) or the right orbitofrontal cortex (rOFC). Suitable candidates have moderate OCD symptoms, have not found success with standard OCD treatments, and are stable on certain medications. As an unphased trial, this study provides a unique opportunity to explore a novel treatment approach for OCD.

Will I have to stop taking my current medications?

The trial requires participants to be stable on Serotonin Re-uptake Inhibitor (SRI) medication for at least 8 weeks before and throughout the study. Other medications may be allowed after review by a TMS specialist.

What prior data suggests that this TMS device is safe for treating OCD?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe for treating Obsessive-Compulsive Disorder (OCD). TMS is a non-invasive treatment, meaning it doesn't involve surgery or entering the body. Studies have found that TMS does not pose major safety concerns for participants.

For the bilateral DMPFC treatment, various trials have tested TMS, and results suggest it is well-tolerated with no major side effects reported. Similarly, for the right-sided OFC treatment, deep TMS has received positive safety reviews. Regulators have even approved this method for OCD, highlighting its safety.

Overall, current research considers both treatments under study to be safe. Side effects are rare, and when they occur, they are usually mild, such as headaches or scalp discomfort. This makes TMS a promising option for those seeking new ways to manage treatment-resistant OCD. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the theta-burst stimulation treatments for Obsessive-Compulsive Disorder (OCD) because they offer a novel, non-invasive approach that targets specific brain areas. Unlike traditional options like SSRIs and CBT, these treatments use either continuous or intermittent theta-burst stimulation to activate the orbitofrontal cortex (OFC) or dorsomedial prefrontal cortex (DMPFC). This targeted brain stimulation could potentially provide faster relief from OCD symptoms compared to the weeks or months needed for standard therapies to take effect. Additionally, these treatments might work for patients who haven't responded well to existing medications or therapy, offering new hope for those struggling with this condition.

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). One study found that TMS led to a 22.7% improvement in OCD symptoms. In this trial, participants will receive TMS targeting different brain areas. One group will receive stimulation on both sides of the dorsomedial prefrontal cortex (DMPFC), which has shown promise in reducing symptoms. Another group will receive stimulation targeting the right orbitofrontal cortex (OFC), which studies indicate can significantly improve obsessions and compulsions. Overall, these findings suggest that TMS, when focused on certain brain areas, might help people with OCD. ^{1 3 4 5 6}

Who Is on the Research Team?

Ian Kratter, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults with moderate to severe OCD who haven't responded well to standard treatments like SRIs or cognitive behavioral therapy. Participants must be stable on SRI medication for at least 8 weeks and able to undergo study procedures. Excluded are those with substance abuse issues, severe depression, bipolar disorder, eating disorders, certain medical conditions like seizures or brain injuries, pregnant or nursing women, and anyone planning CBT during the study.

Inclusion Criteria

I have been taking the same SRI medication for at least 8 weeks and plan to continue during the study.

I understand and can agree to the study's procedures and risks.

Successfully complete the screening forms at the Stanford Center for Cognitive and Neurobiological Imaging (CNI) without any contraindications

Exclusion Criteria

Current moderate or severe Alcohol Usage Disorder or Substance Usage Disorder (except nicotine and caffeine) according to the DSM-5 criteria (assessed only if screening appointment was more than 12 months ago - SCID-5 Module E)

Pregnant or nursing females (assessed via urine dipstick if screening appointment was more than 30 days ago)

I do not have an eating disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated theta-burst stimulation using a TMS device targeting either the DMPFC or rOFC site

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Immediate post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Active bilateral DMPFC
• Active right-sided OFC

Trial Overview The trial tests an accelerated form of Transcranial Magnetic Stimulation (TMS) called theta-burst stimulation in two different brain areas: the dorsomedial prefrontal cortex (DMPFC) and the right orbitofrontal cortex (rOFC). Participants will be randomly assigned to receive treatment at one of these sites.

How Is the Trial Designed?

Group I: right OFC Active Control 1 Intervention

This arm will receive continuous theta-burst stimulation to the right OFC site.

Group II: bilateral DMPFC Active Control 1 Intervention

This arm will receive intermittent theta-burst stimulation to bilateral DMPFC site.

Active bilateral DMPFC is already approved in United States for the following indications:

Approved in United States as BrainsWay Deep TMS for:

• Obsessive Compulsive Disorder (OCD)

Approved in United States as MagVenture TMS for:

• Obsessive Compulsive Disorder (OCD)

Approved in United States as NeuroStar TMS for:

• Obsessive Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

A retrospective analysis of six patients with treatment-resistant OCD showed that continuous theta burst stimulation (cTBS) targeting the supplementary motor cortex may help reduce obsessive-compulsive symptoms, suggesting a potential new treatment avenue.

Despite the promising results, the study highlights the need for further research through randomized, sham-controlled trials with larger participant groups to validate the efficacy of cTBS for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series of Continuous Theta Burst Stimulation Treatment for the Supplementary Motor Area Twice a Day in Patients with Obsessive-Compulsive Disorder: A Real World TMS Registry Study in Japan. Noda, Y., Fujii, K., Tokura, F., et al.[2023]

Intermittent theta burst stimulation (iTBS) of the prefrontal cortex has shown effects on reducing cocaine craving and consumption that are comparable to traditional high-frequency rTMS (15 Hz) in a study of 25 treatment-seeking cocaine addicts.

Both iTBS and 15 Hz rTMS demonstrated similar safety and tolerability profiles, with low dropout rates, suggesting that iTBS could be a more efficient treatment option due to its shorter duration (3 minutes) compared to the 15-minute standard protocol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Theta Burst Stimulation of the Prefrontal Cortex in Cocaine Use Disorder: A Pilot Study. Sanna, A., Fattore, L., Badas, P., et al.[2020]

In a study involving 28 treatment-resistant OCD patients, continuous theta-burst stimulation (cTBS) of the right orbitofrontal cortex did not significantly reduce OCD symptoms after two weeks, indicating that this treatment may not be effective in the short term.

While cTBS was found to be safe and led to a temporary improvement in depressive symptoms in the active group, this effect diminished after six weeks, suggesting that longer treatment durations or different stimulation parameters may be necessary for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous Theta-Burst Stimulation Over the Right Orbitofrontal Cortex in Treatment-Resistant Obsessive-Compulsive Disorder Treatment: A Randomized Sham-Controlled Trial. Liu, W., Shao, H., Liao, J., et al.[2022]

Theta burst stimulation (TBS) has been shown to affect brain connectivity, with continuous TBS (cTBS) generally decreasing functional connectivity and intermittent TBS (iTBS) increasing it, aligning with the expected neuroplasticity effects of long-term depression (LTD) and long-term potentiation (LTP).

Task-related outcomes from TBS are more inconsistent, particularly when applied to the prefrontal cortex, suggesting that individual differences and methodological factors significantly influence the effectiveness and variability of TBS responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the neurobiological effects of theta-burst stimulation (TBS) as measured using functional magnetic resonance imaging (fMRI). Kirkovski, M., Donaldson, PH., Do, M., et al.[2023]

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

Theta-burst stimulation (TBS) shows promise as a rapid and effective treatment for psychiatric disorders, particularly treatment-resistant depression and auditory hallucinations, with studies indicating mild adverse effects but no severe complications like seizures or mania.

The current research on TBS is varied in design and outcomes, highlighting the need for more rigorous sham-controlled studies to better assess its long-term safety and efficacy in treating various psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. Rachid, F.[2019]

In a study involving 30 treatment-resistant OCD patients, continuous theta burst transcranial magnetic stimulation (cTBS) over the supplementary motor area was found to be safe but did not significantly improve OCD symptoms compared to sham treatment.

Both active and sham cTBS groups showed similar responder rates (28% for cTBS vs. 36% for sham) at both the end of treatment and follow-up, indicating that cTBS may not be an effective intervention for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial. Harika-Germaneau, G., Rachid, F., Chatard, A., et al.[2020]

In a pilot study involving 29 OCD patients, continuous theta burst stimulation (cTBS) targeting the bilateral supplementary motor area significantly relieved OCD symptoms in 37.93% of participants, indicating its potential efficacy as a treatment.

The study found that functional connectivity between specific brain regions could predict the effectiveness of cTBS, with a high area under the curve (AUC) of 0.85, suggesting that neuroimaging may help identify which patients are more likely to benefit from this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The functional connectivity predictor of therapeutic effect of continuous theta burst stimulation on obsessive-compulsive disorder: A preliminary study. Li, P., Cheng, J., Fan, Q., et al.[2022]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

In a study involving 33 OCD patients, continuous Theta Burst Stimulation (cTBS) targeting the orbitofrontal cortex (OFC) was found to be well tolerated and led to significant improvements in anxiety symptoms and overall severity of OCD after 10 treatment sessions.

While the treatment showed a notable effect on anxiety and global severity scores, the improvements in obsessive and compulsive symptoms were not statistically significant when controlling for other variables, suggesting that the primary benefit of cTBS may be in reducing anxiety associated with OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study. Dutta, P., Dhyani, M., Garg, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6029675/

Transcranial magnetic stimulation in the treatment of ... Published systematic reviews and meta-analyses– have focused on the overall effectiveness of neurostimulation in OCD, with mixed conclusions. Such reviews have ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S027858462400215X

Transcranial magnetic stimulation for obsessive ... We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6047114/

Transcranial magnetic stimulation in obsessive-compulsive ... TMS is a non-invasive brain stimulation technique that has shown promise as an adjunct treatment for the symptoms of Obsessive-Compulsive Disorder (OCD).

4. nature.com nature.com/articles/s41398-024-03041-4

Continuous theta burst stimulation to relieve symptoms in ... This is the first study with an external validation design across two centers to identify OCD symptoms as playing an important role in cTBS treatment effects.

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.focus.20103

Efficacy and Safety of Deep Transcranial Magnetic ... The primary outcome measure was the change in OCD symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) (20). METHODS. Study ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04286126

Study Details | NCT04286126 | Neuroimaging Biomarkers ... This study evaluates an accelerated schedule of theta-burst stimulation using a Transcranial Magnetic Stimulation (TMS) device for treatment-resistant ...