Clinical trial NCT02311751: rTMS for Executive Function Deficits in Autism Spectrum Disorder
Official title: Repetitive Transcranial Magnetic Stimulation (rTMS) for Executive Function Deficits in Autism Spectrum Disorder and Effects on Brain Structure: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: Autism Spectrum Disorder
Executive Function
rTMS (Repetitive Transcranial Magnetic Stimulation)
MRI (Magnetic Resonance Imaging)
Healthy Subjects
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: Academic Health Science Centres
First posted: 2014-12-08
Enrollment: 40
Sex: ALL
Minimum age (years): 16
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in accuracy on the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory Task
timeFrame: 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 outcomes:
measure: Change in scores on Behaviour Rating Inventory of Executive Functioning (A) (BRIEF) (A)
timeFrame: 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)
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addictions and Mental Health
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Stephanie H Ameis, M.D., M.S.C
role: PRINCIPAL_INVESTIGATOR
References:
citation: Moxon-Emre I, Daskalakis ZJ, Blumberger DM, Croarkin PE, Lyon RE, Forde NJ, Tani H, Truong P, Lai MC, Desarkar P, Sailasuta N, Szatmari P, Ameis SH. Modulation of Dorsolateral Prefrontal Cortex Glutamate/Glutamine Levels Following Repetitive Transcranial Magnetic Stimulation in Young Adults With Autism. Front Neurosci. 2021 Oct 6;15:711542. doi: 10.3389/fnins.2021.711542. eCollection 2021.
citation: Ameis SH, Blumberger DM, Croarkin PE, Mabbott DJ, Lai MC, Desarkar P, Szatmari P, Daskalakis ZJ. Treatment of Executive Function Deficits in autism spectrum disorder with repetitive transcranial magnetic stimulation: A double-blind, sham-controlled, pilot trial. Brain Stimul. 2020 May-Jun;13(3):539-547. doi: 10.1016/j.brs.2020.01.007. Epub 2020 Jan 15.