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

Trial Summary

What is the purpose of this trial?

This trial tests whether combining TMS with ERP therapy can help young people with OCD better manage their compulsions. TMS uses magnetic fields to stimulate brain areas linked to compulsive behavior. The study will compare different types of TMS to see which works best. Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a therapy for severe obsessive-compulsive disorder (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.

What data supports the effectiveness of the treatment TMS + Exposure Therapy for Pediatric OCD?

Research shows that transcranial magnetic stimulation (TMS), when used for obsessive-compulsive disorder (OCD), can significantly reduce symptoms, with over half of patients experiencing a 30% or more reduction in severity. Combining TMS with exposure therapy, which involves facing fears in a controlled way, may enhance these benefits. ^{1 2 3 4 5}

Is TMS + Exposure Therapy safe for pediatric OCD?

The research does not provide specific safety data for TMS combined with Exposure Therapy for pediatric OCD, but exposure-based cognitive-behavioral therapy (CBT) is generally considered safe for treating OCD in children, with no evidence of causing negative effects compared to other treatments. ^{6 7 8 9 10}

How is the TMS + Exposure Therapy treatment for pediatric OCD different from other treatments?

TMS + Exposure Therapy is unique because it combines transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, with exposure therapy, which is the standard psychotherapeutic treatment for OCD. TMS has shown promise in reducing OCD symptoms by targeting specific brain areas, offering a novel approach compared to traditional therapies that primarily focus on behavioral interventions. ^{3 9 11 12 13}

Research Team

Christine Conelea, PhD, LP

Principal Investigator

University of Minnesota

Kristen Benito, PhD

Principal Investigator

Emma Pendleton Bradley Hospital

Eligibility Criteria

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

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

Presence of motor compulsions on CY-BOCS compulsion checklist

I am between 12 and 21 years old.

Exclusion Criteria

Left handedness

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

Inability to undergo MRI

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2022]

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

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

3. 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]

4. United States 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. [2023]

5. 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]

6. United States 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Editorial Perspective: Exposures in cognitive behavior therapy for pediatric obsessive-compulsive disorder: addressing common clinician concerns. [2019]

8. United States 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. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Metacognitive therapy versus exposure and response prevention for pediatric obsessive-compulsive disorder. A case series with randomized allocation. [2018]

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

Stepped care versus standard cognitive-behavioral therapy for obsessive-compulsive disorder: a preliminary study of efficacy and costs. [2021]

11. Switzerland 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. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in obsessive-compulsive disorder: A focus on network mechanisms and state dependence. [2021]

13. England pubmed.ncbi.nlm.nih.gov

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