Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Cognitive Functions and Behavior in Individuals With Autism Spectrum Disorder ( ASD)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Severity level of Autism Spectrum disorders (ASD)
研究概览
简要总结
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.
详细描述
Statement of the Problem:
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Core ASD symptoms include impairments in social communication and restricted and repetitive behaviors, interests, and activities. ASD may also present with secondary signs, including hyperactivity, self-injury, and co-occurrence of some psychiatric conditions, e.g., anxiety and major depression. The symptoms of ASD are persistent and typically appear during the first three years of life. It can be recognized and clinically evident in early childhood.
In most cases, but not all, ASD symptoms might follow a steady course without remission. However, deficits and impairment in social skills and behavioral patterns may not be noticed and diagnosed as symptoms of ASD until the child faces significant life demands such as social, educational, and occupational tasks. Moreover, this functional limitation may vary among persons with ASD and could develop over time.
In the past 50 years, ASD's description has changed from a rare disease of childhood-onset to a well-publicized, advocated, and researched lifelong condition, recognized as relatively common and very heterogeneous. Since the 1970s, several studies have reported increased ASD cases. The report documented that the male/female ratio is approximately 4 per 1. According to the Centers for Disease Control, the prevalence of ASD increased from 1 in 80 (1.25%) in 2011-2013 to 1 in 31 children (3.2%) aged 8 years, and the corresponding figure for the whole of the United States in 2022 was 8 and 9. In the Gulf countries, systematic review studies of the epidemiology of autism revealed a prevalence ranging from 1.4 to 29/10,000 persons. In a study in Taif, Saudi Arabia, the estimated prevalence of autism in primary school children aged 7-12 years was 0.035%. Reviews of the literature have revealed no recent prevalence statistics for children with autism/ASD in Saudi Arabia. The Saudi Ministry of Health has indicated that one in every 160 children has an ASD.
ASDs are a financial, emotional, and social burden. An autistic child's care causes more emotional burden to the parents than that of parents, compared to that of parents taking care of terminally ill children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 5 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Severity level of Autism Spectrum disorders (ASD)
时间窗: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
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.
Blood Biomarker ( Microtubule associated proteins (MAPs) ).
时间窗: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
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
Cognitive function
时间窗: of intervention and 2 week, 3 Months after the last session in intervention for each participant
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.
Autism Spectrum disorder (ASD) Severity level
时间窗: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
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.
Blood Biomarker ( Neuron Specific Enolase (NSE);MYO 16 (myosin XVI); kirre like nephrin family adhesion molecule 3 (KIRREL3) ).
时间窗: pre-intervention and 2 week then 3 Months after the last session in intervention for each participant
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
次要结局
- Sensory Processing(Before the beginning of intervention and 2 week, 3 Months after the last session in intervention for each participant)
- Psychology and behaviours(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)
- Language,Speech and Communication skills(pre-intervention and 2 week then 3 Months after the last session in intervention for each participant)
研究者
Hayfa Ali Alghabban
Principal Investigator
King Saud University