Clinical trial NCT05408793: Effects of Transcranial Pulse Stimulation on ASD
Official title: Evaluating the Efficacy of Transcranial Pulse Stimulation (TPS) on Individuals with Autism Spectrum Disorder (ASD)- a Double-blinded, Randomized, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autism Spectrum Disorder
High-functioning Autism
Keywords: efficacy and safety
transcranial pulse stimulation
Lead sponsor: The Hong Kong Polytechnic University
Sponsor class: OTHER
First posted: 2022-06-07
Enrollment: 32
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized, double-blinded, sham-controlled trial.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the efficacy and tolerability of TPS on young adolescents with ASD. Methods: This is a two-armed, randomized, double-blinded, sham-controlled trial. Sampling: A total number of 36 subjects, aged between 12 to 17, diagnosed with ASD, will be recruited. Individuals with a Childhood of Autism Rating Scale (CARS) score ≤ 30 (i.e., no ASD) will be excluded. Recruitment: Subjects will be recruited from the community. Block randomization will be performed to allocate subjects to either the verum TPS group or the sham TPS group on a 1: 1 ratio. Interventionists and subjects will be blinded in the randomization process. Intervention: Intervention: Six 30-minures TPS sessions will be delivered to the verum TPS group (800 pulse in each session, total: 4800 pulse) in consecutive two weeks. The treatment brain region is targeted at the right temporoparietal junction (rTPJ). The sham- controlled group will be given 6 sham TPS sessions. Data collection: All participants are required to undertake pre-and-post fMRI and resting-MRI before the TPS procedures. Outcomes: Primary outcome of this study is CARS, and secondary outcomes include Autism Spectrum Quotient (AQ), Australian scale for Asperger's syndrome (ASAS), Social Responsive Scale (SRS), Faux Pas Recognition Test (FPRT), Stroop test, working memory, Clinical global impression - severity and improvement scale (CGI-S and CGI -I) and neuroimaging. All outcome measures will be assessed at baseline, two weeks immediately after intervention and at 1-month and 3-months follow-up.

Detailed description: Primary objective:

1. Participants in the verum TPS group will have a significant reduction in CARS score at posttreatment compared with the sham TPS group.

   Secondary objectives:
2. Participants in the verum TPS group will have significant improvement in Autism Spectrum Quotient (AQ), compared with the sham TPS group.
3. Participants in the verum TPS group will have significant improvement in the Social Responsiveness Scale (SRS), compared with the sham TPS group.
4. Participants in the verum TPS group will have significant improvement in Faux Pas Recognition Test, compared with the sham TPS group.
5. Participants in the verum TPS group will have significant improvement in Stroop test, compared with the sham TPS group.
6. Participants in the verum TPS group will have significant improvement in Clinical global impression - severity and improvement scale (CGI-S and CGI -I) compared with the sham TPS group.
7. Participants in the verum TPS group will have significant brain function connectivity at posttreatment fMRI and resting-state MRI compared to the sham TPS group.

Sample size Based on an RCT with similar design, the estimated effect size of rTMS is 0.5. By adapting an ANOVA 2x2 repeated measures with 95% significance and a power of 0.8, a sample size of 36 will be required in total (18 subjects per group).

Research plan and Methodology Methods Trial Design: In this study, the investigators will use a double-blind randomized controlled trial design with two-armed repeated measures. The trial design complies with the Consolidated Standards of Reporting Trials (CONSORT) statement. In this two-armed design, investigators will use TPS as an intervention group and a waitlist control group. A sham-control group is appropriate for comparing the effect of the TPS on the intervention group to that of those not receiving the TPS treatment at the same timepoints Both groups will be measured at baseline (T1), immediately after the intervention (T2), at the 1-month (T3) and 3-month follow-up (T4). Based on the previous studies, a 3-month follow-up is sufficient to assess the long-term sustainability of the TPS intervention.

Intervention (Transcranial Pulse Stimulation) Purpose of the intervention: The key tenets of the TPS intervention is neuromodulation, i.e., using ultrasound-based brain stimulation techniques to modulate the human brain in a focal and targeted manner. Intervention dose: Each participant should have the pre-treatment MRI scan performed in the University Research Facility in Behavioural and Systems Neuroscience, PolyU prior coming to the first intervention session. All participants (both TPS group and the sham-control group) will receive six 30 minute-TPS sessions (800 pulse in each session, total: 4800 pulse) in 2 weeks' time. Participants will be followed up immediately after post-stimulation in Week 2, and at 1-month and 3- month period after the intervention. The investigators believe that a 2-week TPS intervention is sufficient enough to test the effects of TPS on autism symptoms.

Eligibility criteria: Inclusion Criteria:

1. 12 -17 years of age
2. Chinese ethnicity
3. Diagnosis of Autistic Spectrum Disorder that meets the criteria of the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
4. No change in their management including medications or non-pharmacological intervention
5. Currently taking prescribed psychotropic medications for ≥ 3 months

Exclusion Criteria:

1. A DSM-5 diagnosis other than ASD
2. Concomitant major medical or neurological conditions, such as significant global developmental delay, skull defect, abnormal mass or tumor, or epilepsy
3. A CARS score ≤ 30 (i.e., no ASD)

Primary outcomes:
measure: Autism severity
timeFrame: Changes in CARS scores from baseline at 3 months
Secondary outcomes:
measure: Autistic traits
timeFrame: Changes in AQ scores from baseline at 3 months
measure: Social deficits
timeFrame: Changes in SRS from baseline at 3 months
measure: Asperger's Syndrome
timeFrame: Changes in ASAS from baseline at 3 months
measure: Theory of Mind and Social Cognition
timeFrame: Changes in FPRT from baseline at 3 months
measure: Executive Function
timeFrame: Changes in Stroop test from baseline at 3 months
measure: Working memory
timeFrame: Changes in WMTB from baseline at 3 months
measure: Clinical Global Impression
timeFrame: Changes in WMTB from baseline at 3 months
measure: Neuroimaging
timeFrame: MRI will be assessed at baseline at immediately and 2 weeks after post-stimulation
Other outcomes:
Locations:
city: HongKong
country: Hong Kong
facility: School of Nursing HongKongPolyU
Study officials:
affiliation: The Hong Kong Polytechnic University
name: Teris Cheung, PhD
role: PRINCIPAL_INVESTIGATOR
References: