Effects of Transcranial Pulse Stimulation on ASD

The Hong Kong Polytechnic University

Status: Enrolling

Conditions: Autism Spectrum Disorder; High-functioning Autism

Treatments: Device: Transcranial Pulse Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT05408793

HongKongPU_HSEARS20220228005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 36 estimated patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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36 participants in 2 patient groups

Transcranial Pulse Stimulation (TPS group)

Experimental group

Description:

Subjects in the TPS group will be given 6 verum TPS sessions (Pulse: 800 / session) across two weeks time, with 3 sessions per week.

Treatment:

Device: Transcranial Pulse Stimulation

Sham TPS Group

Sham Comparator group

Description:

Subjects in the Sham TPS group will be given 6 sham TPS sessions across two weeks time, with 3 sessions per week.

Treatment:

Device: Transcranial Pulse Stimulation