Effects of rTMS on Cognitive Functions and Behavior in Individuals With Autism Spectrum Disorder

NCT06524310 | Completed DMC FDA Device

• 1 other identifier: rTMS_ASD_SA
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with core symptoms that include impairments in social communication and restricted and repetitive behaviors, interests, and activities. Social cognition is a broad term used to understand, perceive, and interpret information about others and ourselves in a social context. Impairments in social cognition are often highlighted as a potential mechanism underlying social disability in autism spectrum disorder. Repetitive transcranial magnetic stimulation is a noninvasive technique that modulates brain activity through targeted electromagnetic pulses. It's one of the methods used to deliver electrical stimuli through the scalp in conscious humans. Recently, rTMS has not only been used for the treatment of major depressive disorders, but it has also been advanced as a potential therapeutic technique to treat neurologic disorders such as Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, and many other neuropsychiatric disorders. High-order cognitive functions, such as Executive function (EF) and social cognition, rely on neural network oscillations in the gamma frequency (30-80 Hz) band. It has been proposed that GABA-inhibitory interneurons in the dorsolateral prefrontal cortex (DLPFC) contribute to the synchronization of pyramidal neurons, which is necessary for EF performance. Additionally, given the theory of abnormal synaptic plasticity and excitation/inhibition ratio in ASD, as well as the ability of TMS to modify cortical excitability and plasticity, it leads to exploring the therapeutic potential of rTMS in ASD. This study examines the effectiveness of low-frequency rTMS in improving social, cognitive, and sensory function in individuals with ASD. Further understanding of the effect of low-frequency rTMS in altering the cognitive function in ASD individuals with ASD may help to achieve some answers related to the mechanism behind ASD.

Conditions

Autism Spectrum Disorder

Keywords

ASD, Autism Spectrum Disorder; Repetitive Transcranial Magnetic Stimulation , rTMS; Cognitive function; Social cognition; autistic behaviors; social interaction; sensory problems; excitation to inhibition imbalance; glutamate excitotoxicity

Outcome Measures

Primary Outcomes (5)

• Cognitive function

  Measure the cognitive function by using Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task, looking of any Statistical significance changes in this score of cognitive testing by using CANTAB battery in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group.

  of intervention and 2 week, 3 Months after the last session in intervention for each participant

• Severity level of Autism Spectrum disorders (ASD)

  Any Statistical significance change in the severity level of Autism (ASD) , looking for any changes in the score of Childhood Autism Rating Scale,Second Edition (CARS2-ST) in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group. Score will be represented as Total row score and will be interpreted based on the following : for the age between 2-12 years old * (15-29.5) Minimal to no symptoms of autism spectrum disorder * (30 - 36.5) Mild to moderate symptoms of autism spectrum disorder * ( 37 and higher) Severe symptoms of autism spectrum disorder. CARS2-ST Score minimum= 15 and maximum= - , high CARS scores mean a worse outcome.

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

• Autism Spectrum disorder (ASD) Severity level

  Any Statistical significance change in the severity level of Autism (ASD) , looking for any changes in the score of The Social Responsiveness Scale (SRS) teste in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group. Score will be represented as Total T-score and will be interpreted based on the following: * T-score of 59T or less ; the result in the normal range. * T-score of 60T through 75T; the result in the mild to moderate range. * T-score of 76T or higher; The result in the severe range. high SRS T-scores mean a worse outcome.

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

• Blood Biomarker ( Microtubule associated proteins (MAPs) ).

  Any Statistical significance change in the plasma levels of Blood biomarkers in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group. Score will be represented as plasma concentration , Units of Measure: concentration unit pg/ml

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

• Blood Biomarker ( Neuron Specific Enolase (NSE);MYO 16 (myosin XVI); kirre like nephrin family adhesion molecule 3 (KIRREL3) ).

  Any Statistical significance change in the plasma levels of Blood biomarkers in the active rTMS group before and after completion of rTMs sessions and in comparison, with the control group. Score will be represented as plasma concentration , Units of Measure: concentration unit ng/ml

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

Secondary Outcomes (4)

• Psychology and behaviours

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

• Language,Speech and Communication skills

  pre-intervention and 2 week then 3 Months after the last session in intervention for each participant

• Sensory Processing using Sensory Processing Measure (SPM)

  Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant

• Sensory Processing

  Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant

Study Arms (2)

active rTMS group

EXPERIMENTAL

Male and female ASD individuals aged between 5 and 11 years old who have been diagnosed with ASD. They should have a confirmed clinical diagnosis according to the DSM-5. This will be verified by a diagnostic report or direct communication with the diagnosing clinician. Also, with normal hearing based on past hearing screens. Exclusion criteria to ensure participant safety for the rTMS intervention and included: (1) a history of seizures or epileptiform activity; (2) the presence of any metallic implants within the cranium; (3) a history of significant head trauma or loss of consciousness; and (4) the presence of implanted electronic medical devices (e.g., pacemakers, cochlear implants). All participants in both study groups did not stop their medical or behavioral therapy for ASD. However, participants will be instructed to have a consistent medication regimen or behavioral treatment for at least one month before enrollment and throughout the trial.

Device: Stimulation with low frequency rTMS at 1 Hz

wait-list-control group

NO INTERVENTION

Male and female ASD individuals aged between 5 and 11 years old who have been diagnosed with ASD. They should have a confirmed clinical diagnosis according to the DSM-5. This will be verified by a diagnostic report or direct communication with the diagnosing clinician. Also, with normal hearing based on past hearing screens. Exclusion criteria to ensure participant safety for the rTMS intervention and included: (1) a history of seizures or epileptiform activity; (2) the presence of any metallic implants within the cranium; (3) a history of significant head trauma or loss of consciousness; and (4) the presence of implanted electronic medical devices (e.g., pacemakers, cochlear implants). All participants in both study groups did not stop their medical or behavioral therapy for ASD. However, participants will be instructed to have a consistent medication regimen or behavioral treatment for at least one month before enrollment and throughout the trial.

Interventions

Stimulation with low frequency rTMS at 1 Hz DEVICE

Stimulation with low-frequency rTMS at 1 Hz with 90% MT will be applied with a total of 180 pulses each time, which contains 18 trains with ten pulses and an interval of 20 s between any two adjacent trains. The TMS treatment course will be administered twice per week for 9 weeks; the first six treatments will be over the left DLPFC, the second six sessions will be over the right DLPFC, and the remaining six sessions will be placed on the bilateral DLPFC stimulation.

Also known as: NeuroStar TMS Therapy System (Neuronetics, Inc; Malvern, Pennsylvania). with figure of 8- Coil and a special sensory guard ( SenStarTreatment Link).

active rTMS group

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male and female ASD individuals
• age between 5 and 11 years old
• diagnosed with ASD on prior clinical assessment using the American Psychiatric Association's DSM-V criteria and corroborated by assessment using the Autism Diagnostic Observation Schedule (ADOS).
• Normal hearing ability based on past hearing screens.
• Participation will be limited to higher functioning (intelligence quotient \[IQ\] \>70) to maximize successful completion of tested paradigms, maintain alertness/attention, furthermore, the ability to follow instructions.

You may not qualify if:

• Individuals that are known to have epilepsy ( including Hx. of febrile convulsion) or have a family history of epilepsy.
• Any individual with a previous Hx. Of head injuries
• Any individual has been diagnosed with psychiatric illness, including ADHD, depression, psychosis, bipolar disorder, anxiety disorders, or OCD.
• Individuals using a combination of Psychotropic Medications known for their significant seizure threshold lowering potential, for example, and not as a limitation: Bupropion, Citalopram, Duloxetine, Fluoxetine, Fluvoxamine, Mirtazapine, Paroxetine, Sertraline, Venlafaxine, Tricyclics, Olanzapine, Quetiapine, Aripiprazole, Ziprasidone, and Risperidone.
• The presence of metallic objects, e.g., cranium clips or implanted biomedical devices.

Sponsors & Collaborators

• King Saud University: lead

Study Sites (1)

Department of Physiology, Autism Research and Treatment Center (ARTC), King Saud University Medical City (KSUMC)/Collage of Medicine, King Saud University

Riyadh, Riyadh Region, 12372, Saudi Arabia

Location

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Related Links

• Prevalence and clinical characteristics of autism spectrum disorders in school-age children in Taif- KSA

MeSH Terms

Conditions

Autism Spectrum Disorder; Child Development Disorders, Pervasive

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders

Study Officials

• HAYFA A ALGHABBAN, MD,MSc

  Department of physiology, collage of Medicine, King Saud University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the waiting list control design, blinding of participants and their guardians to group allocation was not possible. However, the clinicians performing the outcome assessments were blinded to the participants' group assignments to minimize potential observer bias.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Randomized controlled study with a waiting list control design.

Study Record Dates

• First Submitted: June 30, 2024
• First Posted: July 29, 2024
• Study Start: July 20, 2024
• Primary Completion: April 30, 2025
• Study Completion: September 30, 2025
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)