Clinical trial NCT06040775: Evaluation of Theta Burst Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorder
Official title: Evaluation of Theta Burst Transcranial Magnetic Stimulation as an Adjunct to Standard Therapy in Improving Core Function Deficits in Children 5-15 Year Age With Autism Spectrum Disorder - a Randomized, Double Blind, Sham Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Autism Spectrum Disorder
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2023-09-18
Enrollment: 82
Sex: ALL
Minimum age (years): 5
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate Theta Burst Transcranial Magnetic Stimulation as an adjunct to standard therapy in improving core function deficits in children 5-15 year age with Autism Spectrum disorder. The main question it aims to answer is whether Theta burst Transcranial Magnetic Stimulation would improve core function deficit in children age 5 - 15 years with Autism Spectrum Disorder as an adjunct to standard therapy. Participants will receive patterned transcranial magnetic stimulation- theta burst stimulation for consecutive 7 days with standard therapy and the comparison group would receive standard therapy alone. Outcome in the form of change in obsessive, repetitive behavior would be measured at 1 month from end of therapy

Detailed description: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with varying degrees of severity and symptoms with core deficits in social communication and interaction and repetitive behavior with restricted interests and activities -American Psychiatric Association, 2013. Diagnosis requires fulfilment of DSM V criterion for Autism Spectrum Disorder. ASD is a lifelong disorder with onset in early developmental period and most patients remain severely impaired in terms of psychosocial functioning throughout their adult lives.

Need for exploration of newer treatment modalities - Currently there is no definitive treatment of Autism and for now the management strategies include - Applied Behavioral Analysis (ABA), sensory integration, and structured teaching targeting core deficits which are time taking process and labor intensive from both the caregiver and the provider's perspective. Pharmacotherapy is effective for targeting associated comorbidities like irritability, aggression, destructive behavior or hyperactivity and had the added disadvantage of side effects like sedation. For Complementary and Alternative Medicine strategies, proof of efficacy has not been unestablished for many. In this context Transcranial Magnetic Stimulation, TMS may prove to be a good non-invasive neuromodulation technique and could be an effective tool in the treatment of ASD core manifestations.

Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation technique. It uses electromagnetic induction to generate transient, localized electrical fields in the brain cortex, causes depolarization and firing of local neurons. Acute effects of TMS include phasic activation of neural circuits and prolonged effects of TMS include alteration in Neuroplasticity by change in synaptic efficacy, leading to long term potentiation or long-term depression, this occurs via alteration in neurotropic factor, modulation of cortical excitability, modulation of functional connectivity. The current study aims to explore role of patterned TMS known as Theta Burst Stimulation (TBS)- in which pulses are applied in bursts of three, frequency of 50 Hz and an inter-burst interval of 200 milli seconds. TBS is a patterned form of repetitive transcranial magnetic stimulation (rTMS) modelled after endogenous hippocampal discharge patterns and has been shown to be more efficient than standard rTMS in modulating cortical excitability. The potential advantages of TBS over rTMS, particularly for children with ASD include shorter overall stimulation duration (5minutes in TBS). Also, TBS could be better tolerated overall and perhaps even safer than standard rTMS as sub threshold intensities are given for shorter periods. Effects of TBS on synaptic plasticity occur much more rapidly than with traditional repetitive TMS protocols. It is also less noisy due to lower amplitudes used which may reduce hyper sensory stimulation and may be one of the reasons why TBS could be better tolerated in children with ASD There seems to be converging in implication of role of dorsolateral prefrontal cortex in pathophysiology and aberrant neural circuitry of children with ASD. This study aims to study the effect of TBS as an adjunct to the ongoing standard therapy on core deficits in autism as measured by CY-BOCS - Children's Yale-Brown Obsessive Compulsive Scale, RBS-R - Repetitive Behavior Scale- Revised, social behavior change as measured by SRS-2 - Social Responsiveness Scale- version 2 and overall autistic traits using CARS-2 - Childhood Autism Rating Scale- version 2 at 1 month and 3 month from end of TBS sessions. It also aims to measure parent reported quality of life and adverse event rates participants. Change in cognitive function using Wisconsin card sorting and time to stroop will be used in participants with IQ\>70.

Eligibility criteria: Inclusion Criteria:

1. 5 to 15 year age.
2. Fulfills DSM-V diagnosis of autism spectrum disorder (ASD)

Exclusion Criteria:

1. Secondary causes of autism

   * Global developmental delay, hearing or vision abnormality
   * Structural brain abnormalities on imaging
   * Genetic or syndromic associations- Down's/Fragile X/Rett's syndrome
2. Children on unstable drug regimen- (antipsychotics or anti epileptics) for last 1 months will be excluded
3. Neurological or psychiatric disorder other than comorbid disorders of ASD
4. Uncontrolled epilepsy as defined by seizure frequency \>1/month for preceding 3 months (including diagnosed patients with CSWS/LKS)
5. Severe concurrent illness or disease or unstable medical conditions like pneumonia
6. Any contraindications for TMS Implanted electronic device and non-removable metallic objects near coil e.g., pacemaker, cochlear implant Presence of ferromagnetic metal in the head outside the mouth On medication lowering seizure threshold

Primary outcomes:
measure: Change in core function deficit in obsessive and repetitive behavior between intervention and control arm
timeFrame: 4 weeks +/- 3 days from end of therapy
Secondary outcomes:
measure: Change in core function deficit in social behavior and overall autism score between intervention and control arm
timeFrame: 4 weeks +/- 3 days from end of therapy
measure: Change in core function deficit in social behavior and overall autism score between intervention and control arm
timeFrame: 12 weeks +/- 7 days from end of therapy
measure: Change in parent reported quality of life as assessed by PedsQL score between intervention and control arm
timeFrame: 4 weeks +/- 3 days from end of therapy and 12 weeks +/- 7 days from end of therapy
measure: Describe Adverse events noted in intervention and control arm
timeFrame: 4 weeks +/- 3 days from end of therapy
measure: To describe effect of TBS in clinical tests for executive function using Wisconsin Card Sorting Test (in study population with IQ>70)
timeFrame: at first visit, at 4 weeks +/- 3 days from end of therapy and at 12 weeks from end of therapy
measure: To describe effect of TBS in clinical tests for executive function using Stroop test time(in study population with IQ>70)
timeFrame: at first visit, at 4 weeks +/- 3 days from end of therapy and at 12 weeks from end of therapy
Other outcomes:
Locations:
Study officials:
affiliation: All India Institute of Medical Sciences
name: Sheffali Gulati
role: PRINCIPAL_INVESTIGATOR
References: