rTMS for Executive Function Deficits in Autism Spectrum Disorder

Study Overview
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Brief Summary
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In this study, the investigators will be examining the effects of repetitive transcranial magnetic stimulation (rTMS) on executive function deficits in individuals with autism spectrum disorder. Half of the participants will be chosen by chance to receive active rTMS stimulation while half will be chosen by chance to receive sham rTMS. Sham rTMS will feel the same as active rTMS only there will be no direct brain stimulation. This is necessary to ensure that active rTMS is efficacious in the enhancement of executive function in individuals with autism spectrum disorder. Based on results from a recently published pilot study, the investigators propose that active rTMS treatment will result in a significant improvement in working memory performance compared to sham rTMS treatment.

Detailed Description
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This study is a randomized, double blind, sham controlled study to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for executive function deficits in individuals with autism spectrum disorder between 16 and 25 years of age. The study duration is approximately 3 months, with the rTMS sessions lasting for 4 weeks, 5 times a week, for about 1 hour each. Several scales will be used to assess for symptom severity and adaptive functioning. Cognition will be assessed using a validated battery. This study also involves a type of brain imaging known as magnetic resonance imaging (MRI) at the beginning and at the end of the 4 weeks of daily rTMS to better understand the effects of rTMS on brain structure and function. Investigators will measure the size and connections of different parts of the brain to assess brain structure and blood flow while participants are completing some basic tasks to asses brain function.

Official Title
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Repetitive Transcranial Magnetic Stimulation (rTMS) for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure: A Pilot Study

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Autism Spectrum Disorder (ASD): Are fluent in the English language Have a diagnosis of high functioning ASD (HF-ASD) (i.e., are verbal with an Intelligence Quotient (IQ) ≥ 70) Are competent to consent based on the subjects' ability to provide a spontaneous narrative description of the key elements of the study Are clinically stable as determined by their treating physician, with no medication changes over the past 4 weeks Exclusion Criteria (ASD): Have a history of substance abuse or dependence in the last 6 months or have a positive urine toxicology screen Have a concomitant major medical or neurologic illness Have had a seizure in the past, or have a first-degree relative with epilepsy Have an abnormal clinical EEG Are pregnant or likely to get pregnant during the next 4 weeks Are clinically unstable Are on benzodiazepines or anticonvulsant medication Have a history of rTMS treatment. Inclusion Criteria (Healthy Controls): Are fluent in the English language Competent to consent Exclusion Criteria (Healthy Controls): Have a history of substance abuse or dependence in the last 6 months or have a positive urine toxicology screen Have a major medical or neurologic illness Have a diagnosed learning disorder or impaired academic or adaptive functioning on history Are pregnant Have an IQ < 80 Have a psychiatric diagnosis on diagnostic interview assessments.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active rTMS<br>Active treatment will be delivered at an intensity that is 90% of the resting motor threshold (RMT). Stimulation will be delivered at 20 Hz with 25 simulation trains of 30 stimuli each (i.e., 750 stimuli) and an intertrain interval of 30 sec. Treatment will be applied in sequential order bilaterally to the left and right dorsolateral prefrontal cortex (DLPFC). The order of bilateral stimulation (i.e. right then left or left than right) will be held constant for all 20 treatments. Intervention: Device: Repetitive Transcranial Magnetic Stimulation | Device: Repetitive Transcranial Magnetic Stimulation<br>* rTMS is a non-invasive procedure involving the use of magnetic fields to stimulate nerve cells.<br>* Other names: MagPro x100 series (Medtronic A/S, Copenhagen, Denmark);|
| Sham Comparator: Sham rTMS<br>Sham stimulation will be delivered using the same stimulation parameters and at the site of active treatment, but with only the side-edge resting on the scalp. The coil will be angled 45 degrees way from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g. contraction of scalp muscles) similar to those of active stimulation, but with minimal direct brain effects. Intervention: Device: Repetitive Transcranial Magnetic Stimulation | Device: Repetitive Transcranial Magnetic Stimulation<br>* rTMS is a non-invasive procedure involving the use of magnetic fields to stimulate nerve cells.<br>* Other names: MagPro x100 series (Medtronic A/S, Copenhagen, Denmark);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in accuracy on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory Task | Specifically the investigators will evaluate the changes in spatial working memory scores before and after rTMS treatment. | Baseline; Post rTMS (4 weeks after baseline); One month follow up ( 4 weeks after post rTMS); 6 month follow up (post rTMS); One year follow up (post rTMS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in scores on Behaviour Rating Inventory of Executive Functioning (A) (BRIEF) (A) | Specifically the investigators will evaluate the changes in executive function (EF) scores before and after rTMS treatment. | Baseline; Post rTMS (4 weeks after baseline); One month follow up ( 4 weeks after post rTMS); 6 month follow up (post rTMS); One year follow up (post rTMS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Executive Function, rTMS (Repetitive Transcranial Magnetic Stimulation), MRI (Magnetic Resonance Imaging), Healthy Subjects, Autism Spectrum Disorder