TMS for Autism

Overseen By James McPartland, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Cognitive-affecting drugs

Disqualifiers: Head trauma, Psychiatric illness, Seizures, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized interventional study designed to evaluate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) on neural and behavioral facets of social cognition in adults with autism spectrum disorder (ASD).

Will I have to stop taking my current medications?

Yes, if you are taking prescription medications that may affect cognitive processes, you will need to stop taking them to participate in this trial.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for autism?

Research shows that TMS can improve cognitive outcomes and reduce certain symptoms in people with autism. Studies also suggest that TMS may help with motor function and behavioral improvements, making it a promising treatment option for autism. ^{1 2 3 4 5}

Is TMS safe for use in humans?

TMS, including its variations like theta burst stimulation (TBS), is generally considered safe for humans, with most adverse events being mild. However, there is a slight risk of seizures, and caution is advised, especially with newer protocols like TBS. ^{2 6 7 8 9}

How is the treatment TMS for autism different from other treatments?

TMS (Transcranial Magnetic Stimulation) is unique because it is a non-invasive brain stimulation technique that uses magnetic fields to improve brain function, unlike traditional drug treatments. It specifically targets areas of the brain associated with autism symptoms, potentially improving social communication and cognitive outcomes without the need for medication. ^{1 2 5 10 11}

Research Team

James McPartland, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults aged 18-40 with autism spectrum disorder (ASD) or typical development, able to undergo EEG and eye-tracking tests. It excludes those with major psychiatric illnesses, pregnant women, individuals with an IQ below 80, history of seizures or serious medical conditions, recent drug/alcohol use, prior TMS therapy or investigational drug use within the last 12 weeks.

Inclusion Criteria

Individuals able to participate in an EEG and eye-tracking experiment

I am between 18 and 40 years old, with or without autism.

Exclusion Criteria

Participants who have taken alcohol or recreational drugs within the preceding 24 hours

Participants reporting significant head trauma or serious brain illness

Participants with an IQ (intelligence quotient) below 80

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment of neuropsychological, cognitive, and behavioral function

1 day

1 visit (in-person)

Treatment

Participants receive either real or sham rTMS and undergo EEG and eye-tracking to measure neural and visual attentional social response

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study is testing repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. The goal is to see how rTMS affects social cognition in adults with ASD.

Participant Groups

Group I: Transcranial Magnetic Stimulation - real Active Control 1 Intervention

Participants will receive active TMS during their study visit

Group II: Transcranial Magnetic Stimulation - sham Placebo Group 1 Intervention

Participants will receive sham stimulation during their study visit simulating TMS

Transcranial Magnetic Stimulation (TMS) is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraine Headache Symptoms

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Transcranial magnetic stimulation (TMS) shows promise as a safe treatment for cognitive and behavioral symptoms in intellectually capable individuals with autism spectrum disorder (IC-ASD), with a meta-analysis of 12 studies indicating significant improvements in cognitive outcomes and specific symptoms.

The study highlights the need for improved research methodologies, such as using neuronavigation and targeting different brain regions, to enhance the efficacy of TMS treatments in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Smith, JR., DiSalvo, M., Green, A., et al.[2023]

In a pilot study involving 13 adults with autism spectrum disorder (ASD), intermittent theta burst stimulation (iTBS) applied over the bilateral posterior superior temporal sulcus (pSTS) showed significant immediate improvements in parent-rated autistic symptoms after 5 days of treatment.

The effectiveness of iTBS on cognitive flexibility and clinical symptoms was influenced by individual factors such as baseline social-communicative impairment, cognitive performance, and concurrent psychotropic medication use, highlighting the need for personalized approaches in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. Ni, HC., Lin, HY., Chen, YL., et al.[2022]

Transcranial magnetic stimulation (TMS) targets a core feature of autism spectrum disorder (ASD) by addressing cortical inhibitory imbalances, leading to improved executive function and reduced stimulus-bound behaviors in individuals with ASD.

TMS has been shown to be safe and effective, with benefits increasing with the number of sessions, and it may work even better when combined with neurofeedback, highlighting the need for further research in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Neuropathological Underpinnings and Clinical Correlations. Casanova, MF., Sokhadze, EM., Casanova, EL., et al.[2021]

In a study involving 13 patients with autism and 13 controls, low frequency repetitive transcranial magnetic stimulation (rTMS) was applied twice a week for 3 weeks, leading to significant improvements in event-related potentials and behavioral measures.

The findings suggest that rTMS may enhance the inhibitory function of minicolumns in the brain, indicating its potential as a therapeutic intervention for autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on gamma frequency oscillations and event-related potentials during processing of illusory figures in autism. Sokhadze, EM., El-Baz, A., Baruth, J., et al.[2022]

In a study involving 11 participants with autism spectrum disorders (ASD), repetitive transcranial magnetic stimulation (rTMS) was found to enhance movement-related cortical potentials (MRCPs), indicating improved motor function.

Specifically, rTMS applied to the supplementary motor area (SMA) increased early MRCP components, while stimulation of the left primary motor cortex (M1) affected later components, suggesting that rTMS may influence cortical inhibitory processes to enhance motor activity in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. Enticott, PG., Rinehart, NJ., Tonge, BJ., et al.[2022]

Transcranial magnetic stimulation (TMS) has a reported overall adverse effect (AE) prevalence of 25% in individuals with autism spectrum disorder (ASD), with most AEs being mild and transient, such as headache (10%) and irritability (21%).

No specific risk factors related to ASD were identified that influenced the prevalence of AEs from TMS, suggesting that TMS may be a safe therapeutic option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Huashuang, Z., Yang, L., Chensheng, H., et al.[2022]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

Postmortem studies have found abnormalities in the peripheral neuropil space of cortical minicolumns in individuals with autism spectrum disorder (ASD), suggesting a potential target for treatment.

Repetitive transcranial magnetic stimulation (rTMS) has shown promise in improving motor symptoms, attention, and perceptual binding in ASD, marking it as the first therapeutic approach aimed at addressing core pathologies of the disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autism spectrum disorders: linking neuropathological findings to treatment with transcranial magnetic stimulation. Casanova, MF., Sokhadze, E., Opris, I., et al.[2015]

A multicenter randomized controlled trial is being conducted to evaluate the safety and efficacy of intermittent theta burst stimulation (iTBS) using rTMS on the right temporoparietal junction in 150 adolescents and young adults with autism spectrum disorder (ASD).

The study aims to improve social communication in participants over a 4-week treatment period, with assessments conducted before treatment and at multiple time points up to 6 months post-treatment, ensuring rigorous safety monitoring and ethical compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial. Enticott, PG., Barlow, K., Guastella, AJ., et al.[2021]

References

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

Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. [2023]

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

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. [2022]

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

Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Neuropathological Underpinnings and Clinical Correlations. [2021]

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

Effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on gamma frequency oscillations and event-related potentials during processing of illusory figures in autism. [2022]

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

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. [2022]

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]

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

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

10. Norway pubmed.ncbi.nlm.nih.gov

Autism spectrum disorders: linking neuropathological findings to treatment with transcranial magnetic stimulation. [2015]

11. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial. [2021]