About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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.
Trial design
Parallel
Treatments tested in this trial
repetitive Transcranial Magnetic Stimulation
DevicePediatric patients with ASD and ADHD will be randomized both in active and sham groups.
Treatment groups
Trial outcomes
Primary outcomes
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.
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).
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.
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.
Secondary outcomes
Determining the impact of rTMS on BDNF in Real Groups vs. Sham Groups, through changes in BDNF serum concentration.
BDNF levels in the plasma will be measured using laboratory techniques such as enzyme-linked immunosorbent assay (ELISA) or immunoassay. These assays use antibodies that specifically bind to BDNF, allowing for quantification. The results of the assay will be analyzed to determine the concentration of BDNF in the plasma sample. This concentration will be reported in picograms per milliliter (pg/mL).
Determining the impact of rTMS on GABA in Real Groups vs. Sham Groups, through changes in serum concentration.
Neurotransmitter GABA will be dosed in serum at three different points in time (baseline, post-treatment, and 1 month later), to evaluate the effect of rTMS in modulating its concentration. This neurotransmitter will be quantified by HPLC and mass spectrometry. Concentrations will be reported in nanograms per milliliter (ng/mL) or picomoles per milliliter (pmol/mL), depending on the assay's sensitivity.
Determining the impact of rTMS on glutamate in Real Groups vs. Sham Groups, through changes in serum concentration.
Glutamate will be dosed in serum at three different points in time (baseline, post-treatment, and 1 month later), to evaluate the effect of rTMS in modulating its concentration. This neurotransmitter will be quantified by HPLC and mass spectrometry. Concentrations will be reported in nanograms per milliliter (ng/mL) or picomoles per milliliter (pmol/mL), depending on the assay's sensitivity.
Determining the impact of rTMS on dopamine in Real Groups vs. Sham Groups, through changes in serum concentration.
Dopamine will be dosed in serum at three different points in time (baseline, post-treatment, and 1 month later), to evaluate the effect of rTMS in modulating its concentration. This neurotransmitter will be quantified by HPLC and mass spectrometry. Concentrations will be reported in nanograms per milliliter (ng/mL) or picomoles per milliliter (pmol/mL), depending on the assay's sensitivity.
Other outcomes
Determining the impact of rTMS on Event-related potentials (ERPs) in Real Groups vs. Sham Groups, and intra-groups
ERPs elicited by TMS will be scored by analyzing their latency and amplitude from EEG data collected.
Determining the impact of rTMS on Resting State-EEG in Real Groups vs. Sham Groups, and intra-groups
Fifteen minutes of resting state will be performed. Free epochs will be finally analyzed in terms of Power Spectral Density and Connectivity.
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