Enhancement of Behavioral and Cognitive Outcomes in Autism Spectrum Disorder Via Neurostimulation

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05371912

Enrollment

Registered

2022-05-12

Start date

2022-03-15

Completion date

2024-02-01

Last updated

2025-11-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autism Spectrum Disorder

Brief summary

Autism spectrum disorder (ASD) encompasses a range of limitations in reciprocal social and communicative milestones, as well as restrictive and/or repetitive patterns of behavior which lead to significant functional challenges impacting individuals throughout their lifespan. There are major shortcomings in the existing pharmacological interventions; they are of limited efficacy, target a subset of problematic behaviors, and fail to improve social cognition. To overcome these limitations and improve outcomes, the investigators study the use of neurostimulation to mitigate the social and cognitive manifestations of ASD.

Detailed description

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique that alters cortical excitability by repeated induction of electromagnetic activity. FDA approved for depression, rTMS is a promising tool in the field of neuropsychiatry with an excellent safety profile. A prevailing hypothesis in ASD proposes that mirror neuron dysfunction in the inferior parietal lobule (IPL) contributes to the core deficits. The left and right IPL regions support different social and cognitive functions and moreover, are differentially impacted in ASD. Therefore, it can be expected that enhancing function of the IPL may produce positive but hemispheric-dependent effects on social cognition. The investigators long-term goal in this pilot proposal is to understand whether stimulating IPL with rTMS improves social and cognitive outcomes in ASD. This research, which builds upon our proof-of-concept testing of 4 patients, proposes 10 sessions of rTMS stimulation of the IPL. Participants will be randomized to receive active stimulation to either the left or right-IPL (with sham stimulation to the contralateral side) in a prospective, double-blind protocol during which neither the subject nor the neuropsychologist obtaining and interpreting the outcome measures will have awareness of the rTMS group. For targeting the IPL, which correlates with the Brodmann areas 40/7 on the cortex, the investigators use disposable mapping caps, and for the purpose of blinding, the investigators use a standard shamming technique. Outcome measures include neuropsychological testing administered at baseline, after completion of TMS regime, and three months later. Within this design, the investigators have three aims: Aim 1: Assess the differential effects of rTMS of the left versus right IPL on linguistic abilities and executive function in ASD. Hypothesis: rTMS stimulation of the IPL leads to long term potentiation and hence enhances cognitive performance in a hemispheric dependent manner with left-IPL stimulation enhancing linguistic ability and right-IPL stimulation enhancing executive function. To measure the effects, the investigators will use the Delis-Kaplan Executive Function System Verbal Fluency task (D-KEFS) and two elements of the NIH toolbox: Flanker: a test to measure the inhibitory and attentional facets of Executive Functioning. Dimensional Change Card Sort (DCCS): a task designed to assess cognitive flexibility. The investigators expect improvement in the Flanker and DCCS scores with right IPL stimulation and D-KEFS score improvement with left IPL stimulation. Aim 2: Determine the effects of unilateral rTMS of the IPL on social/behavioral deficits in children and young adults with ASD. Hypothesis: rTMS simulation of the mirror neuron system potentiates similar improvements in social cognition despite hemispheric laterality via separate but related mechanisms. To measure the outcomes of right v/s left unilateral IPL stimulation, the investigators will use two standard scales and compare the numerical values before and after the intervention. The Social Responsiveness Scale - 2nd Edition (SRS2) and the Repetitive Behavior Scale-Revised (RRBs) are validated parent/caregiver-rated scale of social/communication deficits and restricted/repetitive behaviors respectively.

Interventions

DEVICETrans Cranial Magnetic Stimulation

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Masking description

The TMS coil will be placed on the scalp at a 90 degree angle and will be turned on to create the perception of delivering the stimulation to the brain.

Intervention model description

The patients will be randomized at the time of recruitment to either receiving left or right IPL stimulation. A shamming technique will be applied to the opposite hemisphere. Both the patient and the neuropsychologist obtaining and interpreting the outcome measures will be blinded regarding the hemispheric side of rTMS intervention. Only the clinician delivering the rTMS treatment will have a knowledge about the treatment targeting.

Eligibility

Sex/Gender

ALL

Age

5 Years to 25 Years

Healthy volunteers

Inclusion criteria

* Fulfilling the Diagnostic and Statistical Manual for Mental Disorders 5th edition (DSM-V) criteria for ASD and confirmed by Gilliam Asperger Disorder Scale (GADS) * The patient exhibiting adequate understanding and cooperation for the procedure

Exclusion criteria

* Patients with ASD exhibiting significant anxiety or contact avoidance, precluding them from cooperating with the procedure * Children with a known diagnosis of seizures * Presence of any metallic implants or devices in the head or neck area * Pregnant women

Design outcomes

Primary

Measure	Time frame	Description
The Effects of rTMS on Reciprocal Social Awareness	at baseline and 5 weeks of rTMS	Social Responsiveness Scale, Second Edition (SRS-2), Parent/Caregiver form; 65 items scored 0-3; total raw score range 0-195. Higher scores = greater social impairment. This study reports raw totals (not T-scores). Instrument: SRS-2
The Effects of rTMS on Reciprocal Rigid Patterns of Behavior	at baseline and 5 weeks of rTMS	Repetitive Behavior Scale-Revised (RBS-R); 43 items scored 0-3; total raw score range 0-129. Higher scores = more severe restricted/repetitive behaviors. We report total raw scores.

Secondary

Measure	Time frame	Description
The Effect of rTMS on Verbal Fluency	at baseline and 5 weeks of rTMS	Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency; scores converted to age-normed scaled scores (mean 10, SD 3). Higher scores = better verbal fluency/executive function. We report the Total Correct scaled score per the manual.
The Effects of rTMS on Executive Function Using Flanker Task	at baseline and 5 weeks of rTMS	NIH Toolbox Flanker Inhibitory Control and Attention; Age-Adjusted Standard Scores (mean 100, SD 15) reported. Higher scores = better inhibitory control/attention.
The Effects of rTMS on Executive Function	at baseline and 5 weeks of rTMS	NIH Toolbox Dimensional Change Card Sort (DCCS); Age-Adjusted Standard Scores (mean 100, SD 15) reported. Higher scores = better cognitive flexibility.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from outpatient clinics and community referrals. Eligible participants were randomized 1:1 to left-IPL or right-IPL rTMS.

Pre-assignment details

All patients met the diagnostic criteria for autism spectrum disorder. We excluded all patients with history of seizures or metallic devices in the hedonic area.

Participants by arm

Arm	Count
Left IPL Stimulation 8 subjects received TMS on the left inferior parietal lobule(IPL). The average age was 13.3 years. Gender: The participants were all male Race: black, white and Asian	8
Right IPL Stimulation 8 subjects received TMS on the right inferior parietal lobule(IPL). The average age was 13.3 years. Gender: 7 male and 1 female Race: black, white and Asian	8
Total	16

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	3	2

Baseline characteristics

Characteristic	Right IPL Stimulation	Total	Left IPL Stimulation
Age, Categorical <=18 years	7 Participants	13 Participants	6 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	1 Participants	3 Participants	2 Participants
Executive function	86 standard score (higher =better) STANDARD_DEVIATION 22.996	77.273 standard score (higher =better) STANDARD_DEVIATION 21.062	66.8 standard score (higher =better) STANDARD_DEVIATION 14.025
Executive Function	76.8 standard score ( higher=better) STANDARD_DEVIATION 23.784	77.1 standard score ( higher=better) STANDARD_DEVIATION 22.253	77.4 standard score ( higher=better) STANDARD_DEVIATION 23.416
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	2 Participants	4 Participants	2 Participants
Race (NIH/OMB) Black or African American	1 Participants	2 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	5 Participants	10 Participants	5 Participants
reciprocal rigid patterns of behavior	86.667 total raw score (0-129; higher = worse) STANDARD_DEVIATION 14.334	81.727 total raw score (0-129; higher = worse) STANDARD_DEVIATION 13.609	75.8 total raw score (0-129; higher = worse) STANDARD_DEVIATION 11.212
Sex: Female, Male Female	1 Participants	1 Participants	0 Participants
Sex: Female, Male Male	7 Participants	15 Participants	8 Participants
Social Awareness	79.667 total raw score (0-195; higher = worse) STANDARD_DEVIATION 14.624	74.364 total raw score (0-195; higher = worse) STANDARD_DEVIATION 13.515	68 total raw score (0-195; higher = worse) STANDARD_DEVIATION 9.823
verbal fluency	8.5 scaled score ( higher = better) STANDARD_DEVIATION 7.778	6.571 scaled score ( higher = better) STANDARD_DEVIATION 4.65	5.8 scaled score ( higher = better) STANDARD_DEVIATION 3.384

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8
other Total, other adverse events	0 / 8	0 / 8
serious Total, serious adverse events	0 / 8	0 / 8

Outcome results

Primary

The Effects of rTMS on Reciprocal Rigid Patterns of Behavior

Repetitive Behavior Scale-Revised (RBS-R); 43 items scored 0-3; total raw score range 0-129. Higher scores = more severe restricted/repetitive behaviors. We report total raw scores.

Time frame: at baseline and 5 weeks of rTMS