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Cumulative and Booster Effects of Multisession Prefrontal Transcranial Direct Current Stimulation in Adolescents with ASD

Not Applicable
Recruiting
Conditions
Transcranial Direct Current Stimulation
Autistic Spectrum Disorder
Electroencephalography
Booster Effects
Interventions
Device: Active-tDCS
Device: Sham-tDCS
Behavioral: Cognitive training
Registration Number
NCT05492032
Lead Sponsor
The Hong Kong Polytechnic University
Brief Summary

Autism spectrum disorder (ASD) is a pervasive and lifelong developmental disorder that currently affects 1 in 54 children. Individuals with autism are often severely impaired in communication, social skills, and cognitive functions. Particularly detrimental characteristics typical of ASD include the inability to relate to people and the display of repetitive stereotyped behaviors and uncontrollable temper outbursts over trivial changes in the environment, which often cause emotional stress for the children, their families, schools and neighborhood communities. To date, there is no cure for ASD, and the disorder remains a highly disabling condition. Recently, transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique, has shown great promise as an effective and cost-effective tool for reducing core symptoms, such as anxiety, aggression, impulsivity, and poor social communication, in patients with autism. Although the empirical findings in patients with ASD are encouraging, it remains to be determined whether these experimental data can be translated into real-world benefits. An important next step is to better understand the factors affecting the long-term efficacy of tDCS treatment - in particular, the possible risk factors associated with relapse in patients with ASD and the role of booster session tDCS as an add-on treatment to induce long-lasting neuroplastic effects in ASD.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
150
Inclusion Criteria
  • Individuals who are confirmed by a clinical psychologist based on the Diagnostic and Statistical Manual of Mental Disorders-5th Ed (DSM-V) criteria of Autism spectrum disorder and structured interview with their parents or primary caregivers on their developmental history using the Autism Diagnostic Interview-Revised (ADI-R).
  • Individuals with ASD who are comorbid with ADHD symptoms will be included if they were willing to abstain from the use of these medications at least 96 hours before the commencement, until the completion, of the treatment.
  • In view of the fact that neuroadaptation to antipsychotics typically occurs within six months, potential participants who are prescribed antipsychotic medications will only be included if the dosage of the medication remained unchanged for six months or more before the experimental period.
Exclusion Criteria
  • Individuals without a confirmed diagnosis from the clinical psychologist, with a history of other neurological and psychiatric disorders and head trauma, or on psychiatric medication will be excluded from the study.
  • In view of the possibility of seizure induction by tDCS, potential ASD participants comorbid with epilepsy will be excluded.
  • Potential participants comorbid with mood or anxiety disorders will also be excluded.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active booster tDCS treatment vs. Sham booster tDCS treatmentCognitive trainingExperimental group: active multisession tDCS + active booster tDCS vs Active control group: active multisession tDCS + sham booster tDCS To test whether booster treatment cycles of tDCS will prolong the cognitive benefits in individuals with ASD), the primary outcome, the total SRS-2 score, and the secondary outcomes, the E/I ratio and the cognitive composite score at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4), will be compared.
Active cathodal (inhibitory) tDCS vs. Sham-tDCS conditionSham-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether active cathodal \[inhibitory\] tDCS over the left dlPRC will facilitate learning through stimulation and thus improve cognitive function in patients with ASD, the primary outcomes (SRS-2 scores) of the two groups at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4) will be compared.
Active cathodal (inhibitory) tDCS vs. Sham-tDCS conditionCognitive trainingExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether active cathodal \[inhibitory\] tDCS over the left dlPRC will facilitate learning through stimulation and thus improve cognitive function in patients with ASD, the primary outcomes (SRS-2 scores) of the two groups at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4) will be compared.
Active booster tDCS treatment vs. Sham booster tDCS treatmentActive-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: active multisession tDCS + sham booster tDCS To test whether booster treatment cycles of tDCS will prolong the cognitive benefits in individuals with ASD), the primary outcome, the total SRS-2 score, and the secondary outcomes, the E/I ratio and the cognitive composite score at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4), will be compared.
Active booster tDCS treatment vs. Sham booster tDCS treatmentSham-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: active multisession tDCS + sham booster tDCS To test whether booster treatment cycles of tDCS will prolong the cognitive benefits in individuals with ASD), the primary outcome, the total SRS-2 score, and the secondary outcomes, the E/I ratio and the cognitive composite score at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4), will be compared.
Change in EEG E/I ratios in the active tDCS vs. sham tDCS groupsSham-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether enhanced neuronal network organization, as indicated by EEG E/I ratios, in patients with ASD will mediate the beneficial effects of tDCS in terms of improvements in cognitive function, measurements taken at baseline, 1-day and 1-month after tDCS treatment will be compared. The change in EEG E/I ratios in patients in the active tDCS and sham tDCS groups will be compared using E/I ratios averaged from channels Fp1, F3, and F7 to increase the signal-to-noise ratio of the EEG data and to represent the left frontal E/I ratio.
Change in EEG E/I ratios in the active tDCS vs. sham tDCS groupsActive-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether enhanced neuronal network organization, as indicated by EEG E/I ratios, in patients with ASD will mediate the beneficial effects of tDCS in terms of improvements in cognitive function, measurements taken at baseline, 1-day and 1-month after tDCS treatment will be compared. The change in EEG E/I ratios in patients in the active tDCS and sham tDCS groups will be compared using E/I ratios averaged from channels Fp1, F3, and F7 to increase the signal-to-noise ratio of the EEG data and to represent the left frontal E/I ratio.
Active cathodal (inhibitory) tDCS vs. Sham-tDCS conditionActive-tDCSExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether active cathodal \[inhibitory\] tDCS over the left dlPRC will facilitate learning through stimulation and thus improve cognitive function in patients with ASD, the primary outcomes (SRS-2 scores) of the two groups at the start (T0), 1-month (T1), 3-month (T2), 6-month (T3), and at the end of study i.e. 12-months (T4) will be compared.
Change in EEG E/I ratios in the active tDCS vs. sham tDCS groupsCognitive trainingExperimental group: active multisession tDCS + active booster tDCS vs Active control group: sham multisession tDCS + sham booster tDCS To test whether enhanced neuronal network organization, as indicated by EEG E/I ratios, in patients with ASD will mediate the beneficial effects of tDCS in terms of improvements in cognitive function, measurements taken at baseline, 1-day and 1-month after tDCS treatment will be compared. The change in EEG E/I ratios in patients in the active tDCS and sham tDCS groups will be compared using E/I ratios averaged from channels Fp1, F3, and F7 to increase the signal-to-noise ratio of the EEG data and to represent the left frontal E/I ratio.
Primary Outcome Measures
NameTimeMethod
Change in social responsiveness - Social Responsiveness Scale-2nd edition (SRS-2)First day of intervention, 1-month, 3-month, 6-month and 12-months after treatment (5 time points)

SRS-2 is a sensitive measure of social functioning in children that detects even subtle symptoms that are highly related to ASD. It uses a four-point scale and focuses on different aspects of socialization. The total score reflects the clinical effectiveness of tDCS, and higher scores indicate greater symptom severity. It has been shown that SRS-2 is sensitive to detect changes in social communication improvement related to improved cognitive functioning after treatment. SRS-2 assessments will be conducted before and immediately after tDCS treatment.

Secondary Outcome Measures
NameTimeMethod
tDCS safety and clinical response in tDCS outcomeFirst day of intervention, 1-month, 3-month, 6-month and 12-months after treatment (5 time points)

To assess tDCS safety, participants will be asked to complete an adverse effects questionnaire (AEQ) which charts the presence of uncomfortable sensations and changes emotions, cognition and perceptions.

Based on the tDCS outcome recorded immediately after tDCS treatment, participants will be categorized into responders and non-responders based on the percentage of change in the total SRS score. Participants who show reductions of at least 10% in total SRS scores as compared to baseline scores will be considered responders. This percentage reduction benchmark was set with reference to the minimal clinically important difference (MCID) and calculated using the standard error measurement method from an ASD sample in a previous randomized controlled trial.

Change in neuropsychological measures - CANTAB® cognitive testsFirst day of intervention, 1-month, 3-month, 6-month and 12-months after treatment (5 time points)

Cambridge Neuropsychological Test Automated Battery (CANTAB®) includes computerized tests that are correlated to neural networks and have demonstrated high sensitivity in detecting changes in neuropsychological performance. The tests in this battery-the Reaction Time (RTI), Spatial Working Memory (SWM), and Multitasking Tests (MTT)-are well validated and are highly sensitive to the core domains impaired in patients with ASD, including to response/reaction time, working memory, attention, inhibition, and cognitive flexibility.

Change in EEG E/I ratio measurementFirst day of intervention, 1-month, 3-month, 6-month and 12-months after treatment (5 time points)

Each participant will be tested individually using the Starstim 32 hybrid EEG/tCS device (Neuroelectrics®) to collect EEG data. EEG measurements will be taken in the resting state before and immediately after the 10-session intervention program. Participants will be instructed to sit still and focus their attention on a "+" displayed on a computer monitor during eyes-open resting conditions for 5 minutes. Raw data will be processed with the EEGLAB Toolbox using MATLAB® R2019a (The MathWorks Inc., Natick, Massachusetts, USA). Data from 19 electrode positions (Fp1, Fp2, F3, F4, F7, F8, Fz, T3, T4, T5, T6, C3, C4, Cz, P3, P4, Pz, O1, and O2) will be used for analysis.

Trial Locations

Locations (1)

The Hong Kong Polytechnic University

🇭🇰

Hung Hom, Kowloon, Hong Kong

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