rTMS for Autism

Overseen By Pushpal Desarkar, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Pregnancy, Substance use disorder, others

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

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

Compensation: Varies

Number of Visits: 11

Duration: 1 week

150 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking benzodiazepines or anticonvulsants.

What data supports the idea that rTMS for Autism is an effective treatment?

The available research shows that rTMS can be effective for people with autism. One study found that rTMS improved depression symptoms in adults with both autism and depression, and family members noticed improvements in autism symptoms. Another study showed that rTMS helped improve attention and reduce repetitive behaviors and irritability in people with autism. These findings suggest that rTMS could be a promising treatment for autism. ^{1 2 3 4 5}

What safety data exists for rTMS treatment in autism?

Safety data for rTMS, including its use in autism, has been reviewed and updated over the years. Initial safety guidelines were established in 1996, with updates in 2008 and 2021, focusing on potential adverse events, precautions, and dosing considerations. A systematic review highlights that adverse effects in autism have not been fully evaluated, but existing studies suggest rTMS is generally well tolerated. An open-label pilot study found rTMS to be well tolerated in adults with autism and comorbid depression, with mild side effects. Overall, rTMS is considered safe when following established guidelines, though further research is needed specifically for autism. ^{2 6 7 8 9}

Is rTMS a promising treatment for autism?

Yes, rTMS is a promising treatment for autism. It is a non-invasive technique that has shown potential in improving symptoms of autism, such as depression and motor function, with minimal side effects. Studies suggest it could help balance brain activity and improve behavior in individuals with autism. ^{2 3 4 8 10}

What is the purpose of this trial?

In the current project, investigators have two main goals: i) Testing whether an excessive plasticity, i.e. hyperplasticity in the motor cortex underlies motor function difficulties in autistic adults, and ii) Using repetitive Transcranial Magnetic Stimulation (rTMS) with autistic adults to examine whether resulting reduced hyperplasticity in the motor cortex will be associated with clinical improvements in the motor function.

Eligibility Criteria

This trial is for adults with autism who have difficulties with motor functions. Participants should be able to give informed consent and follow the study procedures. Specific details about inclusion or exclusion criteria are not provided, but typically these would outline health conditions or medications that might disqualify someone from participating.

Inclusion Criteria

ASD participants with DSM-5 diagnosis of ASD without intellectual disability confirmed by clinical assessment and ADOS-2

ASD or control participants agreeing to adhere to Lifestyle Considerations throughout study duration

ASD or control participants able to read, write, and communicate effectively in English

Exclusion Criteria

I have a medical condition that might need urgent care.

ASD or control participants with significant hearing or visual impairment interfering with the ability to read or hear instructions

I am currently taking benzodiazepines or anticonvulsants for ASD.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Clinical, adaptive, and motor function assessments, and pre- and post-iTBS session with EEG to assess plasticity

1 week

2 visits (in-person)

Treatment

Randomized, double-blind, sham-controlled rTMS sessions on the motor cortex

1 week

5 visits (in-person)

Immediate Post-Treatment Assessment

Assessment of motor and adaptive function, and plasticity in the motor cortex immediately after the last rTMS session

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in motor function and plasticity 1 and 4 weeks after the last rTMS session

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• rTMS

Trial Overview The study is examining if using repetitive Transcranial Magnetic Stimulation (rTMS) on the motor cortex can improve motor function in autistic adults by reducing hyperplasticity. There's a comparison between active rTMS and sham (placebo-like) treatment.

Participant Groups

Group I: Active rTMS Active Control 1 Intervention

Autistic adults receiving active rTMS to the motor cortex.

Group II: Sham rTMS Placebo Group 1 Intervention

Autistic adults receiving sham rTMS to the motor cortex.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

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

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Findings from Research

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 13 adults with autism spectrum disorder (ASD) and major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) was found to be well tolerated, with mild side effects reported.

Participants experienced a significant reduction in depressive symptoms, with an average improvement of 13.5 points on the Hamilton rating scale for depression, and 40% achieved remission, suggesting rTMS may be an effective treatment for depression in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. Gwynette, MF., Lowe, DW., Henneberry, EA., et al.[2023]

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]

In a study involving 32 autistic children with intellectual disabilities, 1 Hz repetitive transcranial magnetic stimulation (rTMS) was found to significantly improve brain activity, as indicated by changes in electroencephalogram (EEG) measures like recursive rate and deterministic features.

The experimental group receiving rTMS also showed notable improvements in behavior, as reflected in the Autism Behavior Checklist scores, suggesting that rTMS may be a beneficial intervention for enhancing both brain function and behavioral outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 1Hz repetitive transcranial magnetic stimulation on autism with intellectual disability: A pilot study. Kang, J., Zhang, Z., Wan, L., et al.[2022]

After 12 sessions of low-frequency rTMS applied to the dorsolateral prefrontal cortices, individuals with autism spectrum disorder (ASD) showed significant improvements in event-related potentials (N200 and P300) related to selective attention, indicating enhanced cognitive processing.

Participants also experienced a reduction in motor response errors, repetitive behaviors, and irritability, suggesting that rTMS may be a promising therapeutic tool for improving attention and behavioral symptoms in ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism. Casanova, MF., Baruth, JM., El-Baz, A., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a study involving 28 adults with autism spectrum disorder, deep repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex showed a significant reduction in social relating symptoms compared to a sham treatment.

Participants receiving active rTMS also experienced decreased anxiety in social situations, suggesting that this technique may improve both social functioning and emotional responses in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Enticott, PG., Fitzgibbon, BM., Kennedy, HA., et al.[2018]

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]

In a study involving 124 high-functioning children with autism spectrum disorders (ASD), repetitive transcranial magnetic stimulation (rTMS) significantly improved cognitive control and attention, particularly after 18 treatment sessions, as evidenced by enhanced accuracy and reaction times in a visual oddball task.

The treatment also led to notable reductions in aberrant behaviors and improvements in executive functions, suggesting that rTMS may effectively target core features of ASD with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory Study of rTMS Neuromodulation Effects on Electrocortical Functional Measures of Performance in an Oddball Test and Behavioral Symptoms in Autism. Sokhadze, EM., Lamina, EV., Casanova, EL., et al.[2023]

References

1. 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]

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

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. [2023]

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

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

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

Effects of 1Hz repetitive transcranial magnetic stimulation on autism with intellectual disability: A pilot study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. [2018]

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Exploratory Study of rTMS Neuromodulation Effects on Electrocortical Functional Measures of Performance in an Oddball Test and Behavioral Symptoms in Autism. [2023]