TMS + Exposure Therapy for Pediatric OCD

(NExT Trial)

Recruiting at 1 trial location

Overseen By Christine Conelea, PhD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Bradley Hospital

Must not be taking: Seizurogenic medications

Disqualifiers: Epilepsy, Bipolar, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether transcranial magnetic stimulation (TMS) can enhance the effectiveness of exposure therapy (ERP) for young people with Obsessive-Compulsive Disorder (OCD). Researchers aim to determine if TMS can improve brain function related to compulsive behavior and reduce compulsions during therapy. Participants will be divided into three groups to receive either one of two real TMS treatments or a sham (fake) TMS treatment before ERP sessions. Individuals with moderate to severe OCD symptoms and motor compulsions might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve treatment options for OCD.

Will I have to stop taking my current medications?

The trial requires that any medication you are taking must be stable, meaning you have been on the same medication and dose for at least 6 weeks with no planned changes during the study. If your medication has a high risk of causing seizures, you may need to stop taking it.

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

Research shows that transcranial magnetic stimulation (TMS) is safe for people with obsessive-compulsive disorder (OCD). For intermittent theta burst stimulation (iTBS), studies in similar conditions suggest it is generally well-tolerated. One study found high-dose iTBS safe for children with autism, indicating potential safety for young people.

Regarding continuous theta burst stimulation (cTBS), research suggests it can help reduce OCD symptoms. In one study, cTBS targeting a specific brain area was safe and effective in reducing OCD symptoms. Another study supports its safety, showing no significant negative effects in teenagers.

Although these treatments are still under study, research suggests they are generally safe and could help with OCD. Participants have not reported serious side effects, making these treatments promising options for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pediatric OCD because they combine Transcranial Magnetic Stimulation (TMS) with Exposure Therapy, potentially offering faster and more effective relief. Unlike traditional treatments like cognitive-behavioral therapy (CBT) and medications such as SSRIs, these approaches use iTBS or cTBS, targeting specific brain regions to enhance therapy outcomes. The ERP+iTBS arm targets the dorsolateral prefrontal cortex, while the ERP+cTBS arm focuses on the presupplementary motor area, both aiming to improve response to exposure therapy. This innovative combination could lead to quicker symptom reduction, offering a promising alternative to current treatment options.

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

Research shows that transcranial magnetic stimulation (TMS) can help reduce symptoms of Obsessive-Compulsive Disorder (OCD). In this trial, participants in the ERP+iTBS arm will receive intermittent theta burst stimulation (iTBS), a specific type of TMS that significantly lowers OCD symptoms, with noticeable improvements within two weeks. Participants in the ERP+cTBS arm will receive continuous theta burst stimulation (cTBS), another TMS type that improves OCD symptoms, especially when focused on certain brain areas. Both iTBS and cTBS have shown promise in reducing compulsive behaviors in OCD patients, potentially making them effective treatment options when combined with exposure therapy. ^{5 6 7 8 9}

Who Is on the Research Team?

Kristen Benito, PhD

Principal Investigator

Emma Pendleton Bradley Hospital

Christine Conelea, PhD, LP

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for young people aged 12-21 with moderate to severe OCD, as shown by specific test scores. They must speak English and have motor compulsions. It's not for left-handed individuals, those on certain medications or with conditions that increase TMS risks (like epilepsy), pregnant girls not using contraception, anyone unable to undergo MRI, or if they've had psychosis, recent substance abuse, other OCD therapies or TMS treatments recently.

Inclusion Criteria

I have moderate or severe OCD based on a specific test score.

English fluency to ensure comprehension of informed consent and study measures and instructions

Presence of motor compulsions on CY-BOCS compulsion checklist

Exclusion Criteria

Left handedness

I am pregnant or not using effective birth control and am sexually active.

Inability to undergo MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily TMS followed by ERP for two weeks (10 sessions)

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS + Exposure Therapy

Trial Overview The study tests how different types of transcranial magnetic stimulation (TMS) can help improve Exposure with Response Prevention therapy in treating OCD. Participants will receive either active TMS targeting specific brain areas or sham TMS alongside their therapy over two weeks and will be assessed through interviews, questionnaires, tasks and MRIs.

How Is the Trial Designed?

Group I: ERP+iTBS Experimental Treatment 2 Interventions

Participants will receive two weeks (10 sessions) of intermittent theta burst stimulation (iTBS; a form of TMS) targeting the dorsolateral prefrontal cortex (dlPFC), followed immediately by Exposure Plus Response Prevention (ERP).

Group II: ERP+cTBS Experimental Treatment 2 Interventions

Participants will receive two weeks (10 sessions) of continuous theta burst stimulation (cTBS; a form of TMS) targeting the presupplementary motor area (pSMA), followed immediately by Exposure Plus Response Prevention (ERP).

Group III: ERP+Sham Active Control 2 Interventions

Participants will receive two weeks (10 sessions) of sham ("fake") TMS, followed immediately by Exposure Plus Response Prevention (ERP).

TMS + Exposure Therapy is already approved in United States for the following indications:

Approved in United States as TMS for:

• Treatment-resistant depression
• Obsessive-compulsive disorder (adults)

Who Is Running the Clinical Trial?

Bradley Hospital

Lead Sponsor

Trials

22

Recruited

1,900+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

Butler Hospital

Collaborator

Trials

133

Recruited

16,700+

Published Research Related to This Trial

Exposure with response prevention (ERP) for youth with obsessive-compulsive disorder (OCD) has a low attrition rate of 10.24%, which is significantly lower than other treatment modalities like pharmacotherapy (17.29%) and active controls (20.63%).

The study suggests that ERP is an effective first-line treatment for OCD, as attrition is primarily due to logistical issues rather than treatment distress, indicating that concerns about distress leading to dropout are unfounded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of dropout rates from exposure with response prevention and pharmacological treatment for youth with obsessive compulsive disorder. Johnco, C., McGuire, JF., Roper, T., et al.[2022]

Metacognitive therapy (MCT) for children with obsessive-compulsive disorder (OCD) showed clinically and statistically significant improvements in symptom severity after treatment, based on a study involving 10 participants.

The benefits of MCT were maintained at both the 3-month and 2-year follow-ups, suggesting it could be a promising alternative to the traditional exposure with ritual prevention (ERP) therapy for pediatric OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metacognitive therapy versus exposure and response prevention for pediatric obsessive-compulsive disorder. A case series with randomized allocation. Simons, M., Schneider, S., Herpertz-Dahlmann, B.[2018]

Transcranial magnetic stimulation (TMS) shows promise as a non-invasive treatment for Obsessive-Compulsive Disorder (OCD), but its clinical efficacy and reliability in reducing symptoms need further quantification and research.

The effectiveness of TMS may be influenced by factors such as the context of stimulation and individual brain anatomy, suggesting that a more tailored approach using neuroimaging and computational modeling could enhance treatment outcomes for OCD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence. Cocchi, L., Zalesky, A., Nott, Z., et al.[2021]

Exposure-based cognitive-behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD) does not lead to negative outcomes such as treatment attrition, poor therapeutic relationships, or low treatment satisfaction when compared to nonexposure-based treatments.

These findings support expert recommendations for using exposure-based CBT in treating pediatric OCD, helping to alleviate clinician concerns about potential adverse effects on patients and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Editorial Perspective: Exposures in cognitive behavior therapy for pediatric obsessive-compulsive disorder: addressing common clinician concerns. McGuire, JF., Wu, MS., Choy, C., et al.[2019]

Patients with obsessive-compulsive disorder (OCD) show inhibitory deficits in motor cortex excitability compared to control volunteers, as indicated by a meta-analysis of 17 studies, suggesting a potential link to GABAergic deficits in OCD.

Repetitive transcranial magnetic stimulation (rTMS) did not significantly change resting motor threshold in OCD patients, indicating that while rTMS may influence GABAergic function, it does not affect glutamatergic synaptic transmission, which is reflected in this measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor cortical inhibitory deficits in patients with obsessive-compulsive disorder-A systematic review and meta-analysis of transcranial magnetic stimulation literature. Rodrigues da Silva, D., Maia, A., Cotovio, G., et al.[2023]

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]

In a study of 26 patients with obsessive-compulsive disorder (OCD), deep repetitive transcranial magnetic stimulation (dTMS) treatment resulted in a 53.9% response rate, with significant reductions in OCD severity as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 30 treatment sessions.

The study found no significant differences in treatment response based on sex or medication status, and importantly, no adverse events were reported, suggesting that dTMS is a safe and effective option for OCD treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series of Deep Transcranial Magnetic Stimulation Treatment for Patients with Obsessive-Compulsive Disorder in the Tokyo Metropolitan Area. Ikawa, H., Osawa, R., Sato, A., et al.[2022]

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]

Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) has been shown to effectively reduce symptoms of anxiety and depression in patients with obsessive-compulsive disorder (OCD), based on a meta-analysis of 20 studies involving 688 participants.

While rTMS demonstrated a small to medium effect on reducing OCD, anxiety, and depression symptoms, the improvement in anxiety was influenced by changes in OCD severity, indicating a complex relationship between these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Repetitive Transcranial Magnetic Stimulation on Comorbid Anxiety and Depression Symptoms in Obsessive-Compulsive Disorder: A Meta-Analysis of Randomized Sham-Controlled Trials. Thatikonda, NS., Vinod, P., Balachander, S., et al.[2023]

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]

Serious negative consequences (SNC) from exposure and response prevention (ERP) therapy for obsessive-compulsive disorder (OCD) are extremely rare, occurring in only 0.05% of adult clients and 0.01% of youth clients, indicating that ERP is a safe treatment option.

Despite some therapists' concerns, the study found that most therapists are willing to treat harm-related OCD, and improving communication about the safety and rationale of ERP could enhance access to this effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious negative consequences associated with exposure and response prevention for obsessive-compulsive disorder: A survey of therapist attitudes and experiences. Schneider, SC., Knott, L., Cepeda, SL., et al.[2020]

A study involving 30 adults with OCD found that a stepped care approach to exposure and response prevention (ERP) was equally effective as standard ERP, with 67% of stepped care participants achieving significant improvement compared to 50% in the standard group.

The stepped care model significantly reduced treatment costs for patients and payers without compromising treatment efficacy or patient satisfaction, suggesting it could be a more accessible option for OCD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stepped care versus standard cognitive-behavioral therapy for obsessive-compulsive disorder: a preliminary study of efficacy and costs. Tolin, DF., Diefenbach, GJ., Gilliam, CM.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12000664/

A Case Series on the Effect of Continuous Theta Burst ... This study included patients with OCD receiving continuous theta burst stimulation over the supplementary motor area attending a tertiary care centre.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032722006310

The functional connectivity predictor of therapeutic effect of ... cTBS intervention on bilateral SMA can significantly improve the symptoms of medicated OCD patients with moderate severity.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05931913

NCT05931913 | TMS + Exposure Therapy for Pediatric OCD The goal of this clinical trial is to compare different forms of transcranial magnetic stimulation (TMS) for improving the outcomes of Exposure with ...

4. cpn.or.kr cpn.or.kr/journal/download_pdf.php?doi=10.9758/cpn.24.1220

A Case Series on the Effect of Continuous Theta Burst ... Objective: Transcranial magnetic stimulation is an effective treatment modality for obsessive-compulsive disorder (OCD).

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT07065669

Treating Adolescent Obsessive Compulsive Disorder With ... This study's primary goal is to examine whether treatment with two forms of transcranial magnetic stimulation (TMS) called theta burst stimulation (TBS) show ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10223256/

A Case Series of Continuous Theta Burst Stimulation ... The results suggest that treatment with cTBS for the bilateral supplementary motor area may reduce obsessive-compulsive symptoms in patients with OCD.

7. 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.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1876201825000632

Efficacy and safety of accelerated transcranial magnetic ... Accelerated TMS offers promising, faster treatment for OCD and significantly reduces depressive symptoms, though it has no effect on anxiety.

9. journals.sagepub.com journals.sagepub.com/doi/abs/10.1177/09731342241267114

Feasibility and Safety of Accelerated Sequential Theta ... This report details the feasibility and safety of administering sequential accelerated theta burst stimulation (sequential aTBS) in an adolescent with treatment ...