pBFS Guided rTMS Over Cognitive Control Network for ASD

Official title

Repetitive Transcranial Magnetic Stimulation Guided by Personalized Brain Functional Sectors (pBFS) for Low-Functioning Autism Spectrum Disorder: a Multi-center, Randomized, Sham-controlled Trial

Overview

The aim of this trial is to assess the efficacy and safety of precision neuromodulation for alleviating core symptoms in patients with autism spectrum disorder (ASD) who also have intellectual or developmental delay. The neuromodulation will be administered using intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC), guided by personalized Brain Functional Sector (pBFS) technology.

Detailed description

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impaired social communication and repetitive behaviors. Unfortunately, evidence-based treatments have not proven effective for older individuals with low-functioning ASD, despite their significant need for intensive support. However, emerging evidence suggests that Transcranial Magnetic Stimulation (TMS) has been successful in treating various psychiatric and neurological disorders.

Given the broad cognitive control dysfunction observed in ASD, targeting cognitive control function may offer a promising treatment approach. Leveraging the personalized Brain Functional Sector (pBFS) technique and task-free functional MRI scans, we can precisely locate the cognitive control function region within the left DLPFC, and follow-up at 24-week after initiation of treatment.

In this study, participants who meet the inclusion and exclusion criteria will be randomly assigned to either active or sham iTBS (intermittent theta burst stimulation) groups at a ratio of 2:1. The treatment protocol consists of a 12-week duration, with sessions conducted 5 days per week and 3 sessions iTBS over DLPFC per day. The inter-session interval is set at 30 minutes. Clinical evaluations focusing on ASD core symptoms and related behavioral profiles will be conducted at baseline and after the 12-week treatment period.

Interventions

• Device active iTBS treatment
  Participants will undergo three iTBS sessions per day, with 1800 pulses per session, over a 12-week period. Individualized targets will be generated using the pBFS technique.
• Device sham iTBS treatment
  Participants will undergo three iTBS sessions per day, with 1800 pulses per session, over a 12-week period. Sham stimulation will be delivered through a sham coil with the identical appearance as real coil. Individualized targets will be generated using the pBFS technique.

Primary outcome measures

• ADOS-2 SA CSS score change after treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week)]

Secondary outcome measures (8)

• ADOS-2 SA CSS score change from baseline to follow-up [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]
• Response rate in social ability after 12-week iTBS treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week)]
• Response rate in social ability at 24-week follow-up [Time frame: Pre-treatment (baseline), follow-up (24-week)]
• ADOS-2 total CSS change with treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]
• SCQ score change with treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]
• CBCL score change with treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]
• QoL score change with treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]
• AIM score change with treatment [Time frame: Pre-treatment (baseline), post-treatment (12-week), follow-up (24-week)]

Eligibility criteria

Inclusion criteria

• 6-30 years old
• Have the diagnosis of autism spectrum disorder
• ADOS-2 score is higher than the ASD cut-offs
• Comorbid with intelligent disorder, IQ/DQ < 70
• Primary environmental language is Chinese
• Participant's parents or other legal guardians give informed consent

Exclusion criteria

• Genetic Disorders, such as (e.g., Down syndrome, Fragile X syndrome, Rett syndorme), Current or history of severe ADHD, tourette syndrome, psychotic disorders (e.g., schizophrenia, schizoaffective disorder, bipolar disorder)
• Severe self-injury or suicidal behavior exhibited within the past year
• Significant visual, auditory, deafness or motor disability that prevent them from following study procedures
• Current or history diagnosis of epilepsy
• Known severe physical diseases, particularly those affecting the brain
• Metal implantation contradicted by MRI or TMS, such as artificial cardiac pacemakers, stents, cochlear implants
• Respiratory or circulatory conditions increasing sedation risk, such as Apnea syndrome, severe snoring, or other relevant diseases
• All legal guardians are illiterate, unable to read informed documents or complete questionnaires independently
• Received transcranial magnetic stimulation (TMS), transcranial current stimulation (tCS), focused ultrasound (FUS), or other neuromodulation treatment in the last 3 months
• Current participation in other clinical trials

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 6 centers

• Fujian Children's Hospital — Fuzhou
• Fujian Maternity and Child Health Hospital — Fuzhou
• Hebei Provincial Mental Health Center — Baoding
• Xi'an TCM Hospital of Encephalopathy — Xi'an
• Jining Medical University — Jining
• Linyi Hedong Rehabilitation Hospital — Linyi

Identifiers

NCT: NCT06255535 · CPASD05DL_Multicenter

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗