Therapeutic Use of rTMS in Pediatric ASD and ADHD Cohorts

NCT06069323 | Recruiting

• 1 other identifier: 50/CE/2023
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

In this interventional, pilot clinical trial investigators will stimulate the dorsolateral prefrontal cortex (DLPFC) in patients with Autism and ADHD. The goal of the study is to improve Cognition and Executive Functions associated with this brain region and, consequently, ameliorate the core symptoms of the disorders. Specifically, the primary purpose is to establish the efficacy, safety, and tolerability of TMS in pediatric patients with ASD and ADHD. Concurrently, the research aims to uncover the impact of TMS on particular biomarkers associated with the development of these disorders and validate the hypothesis suggesting that the BDNF gene polymorphism (Val66Met) could influence an individual's susceptibility to TMS. Participants will be randomized into the active group and placebo group, to guarantee a real assessment of the impact of neurostimulation on the cognitive, behavioral, and biochemical parameters. Participants will be asked to complete a neuropsychological evaluation and a biological sample collection before and after TMS treatment, and 1-month post-treatment completion.

Conditions

Autism Spectrum Disorder; ADHD; Neurodevelopmental Disorders

Keywords

TMS; NEUROMODULATION; ASD; ADHD; NEUROSTIMULATION; COGNITION; EXECUTIVE FUNCTIONS; DLPFC

Outcome Measures

Primary Outcomes (7)

• Determining the impact of rTMS on Cognitive Functioning in Real Groups versus Sham Groups, through changes in scores of NEPSY-II sub-scales

  The NEPSY-II is a comprehensive neuropsychological battery for children and adolescents ages 3-16. It contains 32 subtests, which are divided into six domains of cognitive functioning: Attention and Executive Functioning; Language; Memory and Learning; Sensorimotor; Social Perception; and Visuospatial Processing. Scores are categorized into standard scores (which usually range from 1 to 19 for each subtest), percentile ranks, and age-equivalent scores. Results are compared to a normative sample to assess a child's performance. Higher scores generally indicate better performance, while lower scores may suggest areas of concern or developmental delay.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Depression in Real Groups vs. Sham Groups, through changes in CDI and MASC scores

  The CDI is a self-report questionnaire designed to assess depressive symptoms in children and adolescents. Each item is rated on a scale, often from 0 to 2 or 0 to 3, with higher scores indicating more severe depressive symptoms. The total score is calculated by summing the individual item scores. Cutoff scores are used to categorize depression severity (e.g., mild, moderate, severe).

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Motor Skills and Coordination in Real Groups vs. Sham Groups, through changes in M-ABC scores

  The Movement Assessment Battery for Children (M-ABC) is a motor assessment tool for children aged 3 to 16. The test includes various motor tasks grouped into three categories: manual dexterity, aiming and catching, and balance. Trained examiners administer the tasks and assign scores based on the child's performance. Scores are typically assigned on a scale of 0 to 5 for each task, with higher scores indicating better motor performance. The overall score is calculated by summing the individual task scores within each category. Lower overall scores may suggest motor skill difficulties or delays. The M-ABC results are often interpreted in conjunction with the child's age and gender, as motor development can vary among children.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Emotional and Behavioral Problems in Real Groups vs. Sham Groups, through changes in CBCL scores

  The Child Behavior Checklist (CBCL) is a questionnaire completed by parents or caregivers to assess a child's behavioral and emotional problems. Parents or caregivers provide responses to a series of questions about the child's behavior and emotions. Each item is assigned a numerical value based on the caregiver's responses. These values are summed to create raw scores for different scales and subscales within the CBCL. The raw scores are then converted into T-scores. T-scores are standardized scores with a mean (average) of 50 and a standard deviation of 10. These scores allow for comparisons with a normative sample of children of the same age and gender. Typically, scores falling within the range of 30 to 70 are considered within the average range. Scores below 30 may indicate below-average functioning, while scores above 70 suggest above-average or potentially concerning behavior.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Adaptive Behaviors in Real Groups vs. Sham Groups, through changes in Vineland Scale scores

  The Vineland is a structured interview with a parent or caregiver, which assesses adaptive behaviors in four main domains: Communication, Daily Living Skills, Socialization, and Motor Skills (optional). The Vineland uses standard scores percentile ranks, and age-equivalent scores to quantify an individual's level of adaptive functioning. Ratings are typically on a scale with options like "unable," "sometimes," "usually," and "always. These scores are based on the person's performance relative to a normative sample of individuals of the same age. The Vineland provides an overall summary score known as the Adaptive Behavior Composite (ABC) score. It represents an individual's general adaptive functioning across all domains. In addition to the ABC score, the Vineland provides subdomain scores for each of the four main domains, allowing for a more detailed assessment of specific areas.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on ADHD symptoms in Real Groups vs. Sham Groups, through changes in Conners scores

  The Conners-3 (Conners 3rd Edition) is a widely used questionnaire for evaluating and measuring ADHD symptoms in children and adolescents. It may be administered to parents, teachers, and sometimes the child or adolescent themselves, depending on their age. The Conners-3 generates standard scores for various scales and indices. These scores are typically presented as T-scores, with a mean of 50 and a standard deviation of 10. T-scores help compare the child's behavior to a normative sample of children of the same age and gender. Higher T-scores indicate more severe symptoms or concerns.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Anxiety in Real Groups vs. Sham

  MASC is a self-report questionnaire designed to assess anxiety symptoms in children and adolescents. Patients rate the frequency of their experiences on a 4-point scale, with higher scores indicating greater anxiety. MASC provides a total anxiety score, reflecting the overall level of anxiety symptoms. Subscale scores may also be considered to examine specific domains of anxiety ( including physical symptoms, harm avoidance, social anxiety, and separation/panic). Higher total scores on MASC indicate more significant anxiety symptoms.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

Secondary Outcomes (11)

• Determining the impact of rTMS on BDNF in Real Groups vs. Sham Groups, through changes in BDNF serum concentration.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on GABA in Real Groups vs. Sham Groups, through changes in serum concentration.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on glutamate in Real Groups vs. Sham Groups, through changes in serum concentration.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on dopamine in Real Groups vs. Sham Groups, through changes in serum concentration.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on serotonin in Real Groups vs. Sham Groups, through changes in serum concentration.

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

Other Outcomes (2)

• Determining the impact of rTMS on Event-related potentials (ERPs) in Real Groups vs. Sham Groups, and intra-groups

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

• Determining the impact of rTMS on Resting State-EEG in Real Groups vs. Sham Groups, and intra-groups

  Baseline; Post rTMS (9 weeks after baseline); One month follow-up (4 weeks after rTMS)

Study Arms (4)

Active ASD group

ACTIVE COMPARATOR

The rTMS will be administered 18 times, twice per week, with the following stimulation parameters: 1.0 Hz frequency, 90% MT, 180 pulses per session with 9 trains of 20 pulses each with 20-30s intervals between the trains.

Device: repetitive Transcranial Magnetic Stimulation

Sham ASD group

SHAM COMPARATOR

18 rTMS sessions will be administered, placing the coil perpendicular to the scalp of the stimulation site, to avoid stimulation.

Device: repetitive Transcranial Magnetic Stimulation

Active ADHD group

ACTIVE COMPARATOR

The rTMS will be administered 18 times, twice per week, with the following parameters: 5-10 Hz frequency, 90% MT, 180 pulses per session with 9 trains of 20 pulses each with 20-30 s intervals between the trains.

Device: repetitive Transcranial Magnetic Stimulation

Sham ADHD group

SHAM COMPARATOR

18 rTMS sessions will be administered, placing the coil perpendicular to the scalp of the stimulation site, to avoid stimulation.

Device: repetitive Transcranial Magnetic Stimulation

Interventions

repetitive Transcranial Magnetic Stimulation DEVICE

Pediatric patients with ASD and ADHD will be randomized both in active and sham groups.

Also known as: rTMS, Neurostimulation, Neuromodulation

Active ADHD group; Active ASD group; Sham ADHD group; Sham ASD group

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have received a diagnosis of "ASD" or "ADHD" according to the Diagnostic and Statistical Manual of Mental Disorder-Fifth edition.
• Patients must be older than 6-7 years of age, to obtain their collaboration easily

You may not qualify if:

• presence of known neurological or genetic conditions that are known to affect brain function and structure (i.e. brain tumors, X-fragile, tuberous sclerosis, etc.).
• prescription of psychoactive medication(s) less than 4 weeks prior to joining the study.
• medical history of head trauma associated with prolonged loss of consciousness.
• presence of epilepsy, or history of previous epilepsy, seizures, and repeated febrile seizures.
• presence of comorbidity with psychosis disorder.
• presence of known endocrine, cardiovascular, pulmonary, liver, kidney, or other medical diseases.
• vision and auditory impairment.
• presence of diagnosed chronic or acute inflammation and/or infection.
• lack of consent.

Sponsors & Collaborators

• Ospedali Riuniti di Foggia: lead

Study Sites (1)

Neuropsychiatric Unit for Child and Adolescent, at General Hospital "Riuniti" of Foggia, University of Foggia

Foggia, 71122, Italy

RECRUITING

Related Publications (29)

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MeSH Terms

Conditions

Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Neurodevelopmental Disorders

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Anna N Polito, MD

  Neuropsychiatric Unit for Child and Adolescent, at General Hospital "Riuniti" of Foggia

  STUDY CHAIR

Central Study Contacts

Rosa Savino, MD

CONTACT

+ 39 0881732363; rosa.savino@unifg.it

Giuseppe Cibelli, Prof

CONTACT

+ 39 0881588034; giuseppe.cibelli@unifg.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A double-blind randomized, placebo-controlled study

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: October 5, 2023
• Study Start: June 1, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 5, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

IT (1)