Autism Spectrum Disorder (ASD)NCT07182331
Brain Stimulation and Sensory Integration in Children With ASD
A study testing Continuous Theta Burst Stimulation to Bilateral DLPFC in people with Autism Spectrum Disorder (ASD), run by Neurolab Plus at 2 sites in Kazakhstan.
Trial summary
The goal of this clinical trial is to find out if brain stimulation can help improve sensory integration in children ages 6 to 12 with autism spectrum disorder (ASD). The main questions it aims to answer are: Does brain stimulation using continuous theta-burst stimulation (cTBS) on bilateral dorsolateral prefrontal… Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Autism Spectrum Disorder (ASD)
- What is being tested?
- Continuous Theta Burst Stimulation to Bilateral DLPFC
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesKazakhstan
- Study dates
- 25 Aug 2025to Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged 6-12 years at the time of enrollment.
- Clinical diagnosis of Autism Spectrum Disorder (ASD) confirmed using the Autism Diagnostic Interview-Revised (ADI-R).
- Intelligence quotient (IQ) ≥ 70 as measured by the General Ability Index (GAI) from the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V).
- Ability to understand and follow simple instructions for behavioral tasks and stimulation procedures.
- Stable medication regimen (if any) for at least 4 weeks before the start of the study.
- Written informed consent from a parent or legal guardian, and assent from the child when appropriate.
Who cannot join
- History of epilepsy, seizures, or abnormal EEG suggestive of seizure risk.
- Presence of metal implants, devices, or foreign bodies in or near the head (except dental fillings) that are contraindicated for TMS or MRI.
- Serious neurological disorders other than ASD (e.g., cerebral palsy, brain injury, neurodegenerative disease).
- Severe psychiatric disorders requiring hospitalization or urgent intervention.
- Current or past history of significant head trauma with loss of consciousness > 5 minutes.
- Uncorrected hearing or vision problems that could interfere with task performance.
- Inability to tolerate sitting still for 15-20 minutes.
- Participation in another interventional clinical trial within the past 3 months.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Kazakhstan2 sites
Neurolab Plus
Almaty, 050000
Non-profit joint-stock company "Al-Farabi Kazakh National University"
Almaty, 050040
About this study
Official title: Effects of cTBS on Sensory Integration in Children With Autism Spectrum Disorder: A Randomized, Sham-Controlled Study Integrating Genetic Markers, MRI, fNIRS, and Temporal Binding Tasks
The goal of this clinical trial is to find out if brain stimulation can help improve sensory integration in children ages 6 to 12 with autism spectrum disorder (ASD). The main questions it aims to answer are:
Does brain stimulation using continuous theta-burst stimulation (cTBS) on bilateral dorsolateral prefrontal cortex (DLPFC) improve how children process sights and sounds together? Can brain functioning, structure, and genetics help predict who responds best to this treatment?
Read more
Researchers will compare the results of the randomly assigned active brain stimulation to sham (inactive) stimulation groups to see if the treatment works.
Participants will:
Receive 10 sessions of either active or sham cTBS over 2 weeks Complete a sensory task involving flashes and beeps before and after stimulation Take part in brain scans, namely magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), and provide a saliva sample for genetic testing
Read the detailed description
This study explores how noninvasive brain stimulation may support children with Autism Spectrum Disorder (ASD) by improving how their brains process and combine sounds and images. It also investigates whether changes in brain function, brain structure, and specific genes can help predict how well a child might respond to this type of stimulation. The study is focused on a core challenge in ASD: differences in how children experience sensory input-especially how their brains process what they see and hear together.
The central concept in this research is something called the Temporal Binding Window (TBW). TBW refers to the brief time window in which the brain naturally fuses sensory information from different senses-like sight and sound-into a single event. For most people, this window is quite narrow: sounds and images that are even slightly out of sync are perceived as separate. But in many children with ASD, this window is wider. That means they may confuse the order or timing of sensory inputs, which can affect communication, behavior, and learning.
To address this, the study uses a method called transcranial magnetic stimulation (TMS). This technique delivers brief, painless pulses of magnetic energy to the surface of the brain using a special coil held against the scalp. The type of TMS used here is called continuous theta burst stimulation (cTBS), which delivers rapid bursts of magnetic pulses designed to gently decrease the excitability of targeted brain areas. In this study, cTBS is used to modulate activity in a region called the dorsolateral prefrontal cortex (DLPFC), which is important for regulating attention, working memory, and sensory control.
A total of 40 children between the ages of 6 and 12 will take part. All participants must have a formal diagnosis of ASD, confirmed using a structured caregiver interview known as the Autism Diagnostic Interview - Revised (ADI-R). They must also demonstrate average or above-average cognitive ability, based on a two-subscale IQ measure from the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V). This ensures that all children can understand the tasks and safely undergo the procedures.
Participants are randomly assigned to one of two groups: an active TMS group or a sham TMS group. In the sham group, the same equipment is used, but no actual magnetic stimulation reaches the brain. This allows researchers to compare outcomes while keeping the children, their families, and the staff unaware of group assignments.
Each child completes ten sessions of either active or sham TMS, over approximately two weeks. The stimulation is applied alternately to the left and right sides of the forehead area, corresponding to the DLPFC. Each session lasts only a few minutes. The stimulation is calibrated individually using a simple test to determine the strength needed to trigger a small movement in the child's hand. All children wear ear protection and are supervised closely by trained staff.
The main outcome of the study is a measure of how well children can process timing between visual and auditory signals. This is assessed using a behavioral task known as the Sound-Induced Flash Illusion (SIFI). In this task, the child looks at a screen and hears beeps while seeing flashes of light. Sometimes there is only one flash, but if it is paired with two quick beeps, some children perceive two flashes instead of one. By changing the timing between the flash and the beeps, researchers can measure the range of delays where the child still experiences the illusion. This range is called the Temporal Binding Window. The wider the window, the more likely the child's brain is to "fuse" signals that actually happened at different times. This task is performed before and after the TMS intervention.
In addition to this behavioral task, the study uses two caregiver questionnaires to track any changes in symptoms:
The Autism Treatment Evaluation Checklist (ATEC) is a brief form filled out by parents. It includes four sections: communication skills, social behavior, sensory awareness, and physical health. It is used to detect broad changes in behavior and well-being.
The Short Sensory Profile (SSP) is another caregiver questionnaire that focuses on how children respond to sensory experiences. It includes questions about sensitivity to touch, sound, movement, and visual stimuli.
These tools are chosen because they are simple, validated, and commonly used in ASD research. They are also sensitive to changes in daily functioning and sensory behavior.
To explore how brain function might change as a result of stimulation, the study uses a technique called functional near-infrared spectroscopy (fNIRS). This is a safe, quiet, and noninvasive method that measures how much oxygen is in the blood within specific brain regions. The child wears a soft cap with small sensors that shine near-infrared light into the scalp. This light reflects back differently depending on how much oxygen is being used in the brain underneath. The sensors are placed over the same area that receives the stimulation (the prefrontal cortex), and the recording is done while the child sits quietly with eyes open. There is no task or performance required-this is simply a measurement of the brain's resting state. Recordings are done once before the stimulation begins and again after the final session.
The study also includes a one-time brain scan using magnetic resonance imaging (MRI). MRI provides a detailed image of the structure of the brain, including its size, shape, and thickness in different regions. This helps researchers look for any physical brain characteristics that might explain differences in sensory processing or predict whether a child will respond to the stimulation. The scan is done in a hospital or imaging center using standard pediatric procedures. Children are given headphones, padding, and visual aids to help them feel comfortable and reduce movement. They do not receive any injections or medications.
Finally, the study includes a one-time saliva collection to analyze DNA. This is done using a small sterile tube into which the child spits or where saliva is collected using a swab. The sample is stored and later processed in a genetics lab. Researchers analyze specific single-nucleotide polymorphisms in genes known to be involved in brain development and sensory processing. These include genes such as SHANK3, CNTNAP2, NRXN1, and SCN2A. The goal is to determine whether certain gene variants are associated with differences in how children respond to the stimulation or process multisensory information. This part of the study is exploratory and does not involve returning results to families.
All procedures are conducted in compliance with safety guidelines for pediatric brain stimulation and neuroimaging. Children are monitored throughout the study, and staff are trained to recognize and manage any discomfort or side effects. The TMS procedures are designed to be brief, well-tolerated, and minimally invasive. Participation is voluntary, and families can withdraw at any time.
This research is part of a broader effort to develop personalized approaches to brain stimulation in children with developmental conditions. By combining behavioral tasks, brain imaging, and genetics, the study aims to understand which children are most likely to benefit from neuromodulation and how their sensory systems can be supported. The long-term goal is to inform clinical interventions that are evidence-based, child-centered, and tailored to individual needs.
This study is conducted at a research site in Almaty, Kazakhstan and is funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan under grant number IRN BR27198099. Ethical approval was obtained from the Local Ethical Committee of Al-Farabi Kazakh National University (Protocol No. IRB-A843). The study does not involve U.S. FDA-regulated products and is not conducted under an IND or IDE.
- Conditions
- Autism Spectrum Disorder (ASD)
- Being tested
- Continuous Theta Burst Stimulation to Bilateral DLPFC, Sham Continuous Theta Burst Stimulation
- Keywords
- Transcranial Magnetic Stimulation, Theta Burst Stimulation, Pediatric Neurostimulation, Neurodevelopmental Disorders, Multimodal Biomarkers, Electrophysiology, Functional Near-Infrared Spectroscopy, Magnetic Resonance Imaging, Genetic Markers, Randomized Controlled Trial, Sham-Controlled Trial, Child Neuropsychology, Autism Spectrum Disorder, Sensory Processing, Audiovisual Integration, Temporal Binding Window, Sound-Induced Flash Illusion, Temporal Perception
- Medical subject headings
- Autism Spectrum Disorder, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Theta Burst Stimulation to Bilateral DLPFCDevice
Also called cTBS
Participants receive continuous theta burst stimulation (cTBS) targeting both the left and right dorsolateral prefrontal cortex (DLPFC) during each session. Each hemisphere is stimulated with 600 pulses (triplets at 50 Hz repeated at 5 Hz) over ~40 seconds, at 80% of the individual's active motor threshold. Sessions are administered once daily over 10 treatment days.
Sham Continuous Theta Burst StimulationDevice
Also called Sham cTBS
Participants receive sham continuous theta burst stimulation (cTBS) to both the left and right dorsolateral prefrontal cortex (DLPFC) using a placebo coil that mimics the auditory and tactile sensations of real stimulation but does not produce a magnetic field capable of affecting brain activity. Coil positioning, session timing, and procedure match the active cTBS protocol, including consecutive stimulation to both hemispheres. Both participants and TMS technicians wear earplugs to mask subtle sound differences between active and sham coils. This setup maintains participant and operator blinding and controls for placebo-related effects.
| Study group | Role | What they receive |
|---|---|---|
| Active cTBS to Bilateral DLPFC | Experimental | Participants receive active continuous theta burst stimulation (cTBS) targeting both the left and right dorsolateral prefrontal cortex (DLPFC) during each session. Stimulation is delivered consecutively to both hemispheres using a standard cTBS protocol: 600 pulses per side (triplet bursts at 50 Hz, repeated at 5 Hz), with each hemisphere receiving stimulation over approximately 40 seconds, at 80% of the individual's active motor threshold. A total of 10 bilateral sessions are delivered over two weeks. Receives: Device: Continuous Theta Burst Stimulation to Bilateral DLPFC |
| Sham cTBS to Bilateral DLPFC | Sham comparator | Participants receive sham stimulation to both the left and right DLPFC during each session. Procedures mimic the active condition, including coil placement, session duration, and auditory cues, but no effective magnetic pulses are delivered. Each participant completes 10 bilateral sham sessions over two weeks. The protocol maintains blinding to control for placebo effects and procedural expectations. Receives: Device: Sham Continuous Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Temporal Binding Window (TBW) Width Measured Using the Sound-Induced Flash Illusion (SIFI) Task
The TBW reflects the time interval within which auditory and visual stimuli are integrated as a single percept. It is assessed by computing the proportion of illusion-consistent responses across varying stimulus onset asynchronies in the SIFI task. A reduction in TBW width, measured in milliseconds (ms) following stimulation indicates improved multisensory temporal precision.
Measured: Baseline and up to 7 days after the final TMS session.
Secondary outcomes (4)
Change in Sensory Processing Profile (Short Sensory Profile, SSP)
Parent-reported Short Sensory Profile (SSP; total score range: 38-190). Lower scores indicate greater difficulties with sensory processing. Changes in total and subscale scores will be reported.
Measured: Baseline and up to 7 days after the final TMS session.
Change in Autism Symptom Severity (Autism Treatment Evaluation Checklist, ATEC)
Parent-reported Autism Treatment Evaluation Checklist (ATEC; total score range: 0-179). Higher scores indicate greater severity. Subscales include communication, sociability, sensory/cognitive awareness, and health/physical behavior.
Measured: Baseline and up to 7 days after the final TMS session.
Change in Resting-State Prefrontal Activity - Mean Oxygenation (fNIRS)
Description: Resting-state functional near-infrared spectroscopy (fNIRS) measurement of mean oxygenated hemoglobin (HbO, µM) in the dorsolateral prefrontal cortex (DLPFC).
Measured: Baseline and up to 7 days after the final TMS session.
Change in Resting-State Prefrontal Activity - Functional Connectivity (fNIRS)
Resting-state fNIRS measurement of connectivity indices across DLPFC channels (e.g., correlation coefficients between HbO time series).
Measured: Baseline and up to 7 days after the final TMS session.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2025
- Study start25 Aug 2025
- Primary completionMar 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum Disorder (ASD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Neurolab Plus
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Al-Farabi Kazakh National University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07182331
- Sponsor's protocol ID
- 2.2.6.1
- Other IDs
- BR27198099
- Status last verified
- Aug 2025
- First submitted
- 20 Aug 2025
- Last updated
- 19 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD), including demographics, baseline and outcome measures from the Sound-Induced Flash Illusion (SIFI) task, Autism Treatment Evaluation Checklist (ATEC), Short Sensory Profile (SSP), genetic markers (saliva DNA sequencing results limited to specified polymorphisms), structural MRI volumetric data, fNIRS prefrontal oxygenation measures, and TMS stimulation parameters, will be shared.
Publications
Siemann JK, Veenstra-VanderWeele J, Wallace MT. Approaches to Understanding Multisensory Dysfunction in Autism Spectrum Disorder. Autism Res. 2020 Sep;13(9):1430-1449. doi: 10.1002/aur.2375. Epub 2020 Sep 1.
PubMed 32869933Wallace MT, Stevenson RA. The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities. Neuropsychologia. 2014 Nov;64:105-23. doi: 10.1016/j.neuropsychologia.2014.08.005. Epub 2014 Aug 13.
PubMed 25128432Qiu S, Qiu Y, Li Y, Cong X. Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses. Transl Psychiatry. 2022 Jun 15;12(1):249. doi: 10.1038/s41398-022-02009-6.
PubMed 35705542Camasio A, Panzeri E, Mancuso L, Costa T, Manuello J, Ferraro M, Duca S, Cauda F, Liloia D. Linking neuroanatomical abnormalities in autism spectrum disorder with gene expression of candidate ASD genes: A meta-analytic and network-oriented approach. PLoS One. 2022 Nov 28;17(11):e0277466. doi: 10.1371/journal.pone.0277466. eCollection 2022.
PubMed 36441779Wang H, Ma ZH, Xu LZ, Yang L, Ji ZZ, Tang XZ, Liu JR, Li X, Cao QJ, Liu J. Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis. Child Adolesc Psychiatry Ment Health. 2022 Jan 31;16(1):7. doi: 10.1186/s13034-022-00443-4.
PubMed 35101065Sokhadze EM, Lamina EV, Casanova EL, Kelly DP, Opris I, Tasman A, Casanova MF. Exploratory Study of rTMS Neuromodulation Effects on Electrocortical Functional Measures of Performance in an Oddball Test and Behavioral Symptoms in Autism. Front Syst Neurosci. 2018 May 28;12:20. doi: 10.3389/fnsys.2018.00020. eCollection 2018.
PubMed 29892214Casanova MF, Sokhadze EM, Casanova EL, Opris I, Abujadi C, Marcolin MA, Li X. Translational Neuroscience in Autism: From Neuropathology to Transcranial Magnetic Stimulation Therapies. Psychiatr Clin North Am. 2020 Jun;43(2):229-248. doi: 10.1016/j.psc.2020.02.004. Epub 2020 Apr 8.
PubMed 32439019Foss-Feig JH, Kwakye LD, Cascio CJ, Burnette CP, Kadivar H, Stone WL, Wallace MT. An extended multisensory temporal binding window in autism spectrum disorders. Exp Brain Res. 2010 Jun;203(2):381-9. doi: 10.1007/s00221-010-2240-4.
PubMed 20390256Hardan AY, Libove RA, Keshavan MS, Melhem NM, Minshew NJ. A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biol Psychiatry. 2009 Aug 15;66(4):320-6. doi: 10.1016/j.biopsych.2009.04.024. Epub 2009 Jun 11.
PubMed 19520362Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Baekvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Naerland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnstrom K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Davey Smith G, Stefansson H, Steinberg S, Stevens CR, Sullivan PF, Turley P, Walters GB, Xu X; Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium; BUPGEN; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 23andMe Research Team; Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Borglum AD. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019 Mar;51(3):431-444. doi: 10.1038/s41588-019-0344-8. Epub 2019 Feb 25.
PubMed 30804558Gavin N, Hirst RJ, McGovern DP. The magnitude of the sound-induced flash illusion does not increase monotonically as a function of visual stimulus eccentricity. Atten Percept Psychophys. 2022 Jul;84(5):1689-1698. doi: 10.3758/s13414-022-02493-4. Epub 2022 May 13.
PubMed 35562629De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimaki T, Lin CF, Ma'ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnstrom K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Ruther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK; DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium; Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 Nov 13;515(7526):209-15. doi: 10.1038/nature13772. Epub 2014 Oct 29.
PubMed 25363760Casanova MF, Sokhadze EM, Casanova EL, Li X. Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Neuropathological Underpinnings and Clinical Correlations. Semin Pediatr Neurol. 2020 Oct;35:100832. doi: 10.1016/j.spen.2020.100832. Epub 2020 Jun 24.
PubMed 32892959Barth B, Rohe T, Deppermann S, Fallgatter AJ, Ehlis AC. Neural oscillatory responses to performance monitoring differ between high- and low-impulsive individuals, but are unaffected by TMS. Hum Brain Mapp. 2021 Jun 1;42(8):2416-2433. doi: 10.1002/hbm.25376. Epub 2021 Feb 19.
PubMed 33605509
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of cTBS on Sensory Integration in Children With Autism Spectrum Disorder: A Randomized, Sham-Controlled Study Integrating Genetic Markers, MRI, fNIRS, and Temporal Binding Tasks
- ClinicalTrials.gov ID
- NCT07182331
- Acronym / sponsor ID
- 2.2.6.1
- Conditions
- Autism Spectrum Disorder (ASD)
- Keywords
- Transcranial Magnetic Stimulation, Theta Burst Stimulation, Pediatric Neurostimulation, Neurodevelopmental Disorders, Multimodal Biomarkers, Electrophysiology, Functional Near-Infrared Spectroscopy, Magnetic Resonance Imaging
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Neurolab PlusIndustry (pharma, biotech, devices)
- Collaborators
- Al-Farabi Kazakh National University
- Study start
- 25 Aug 2025 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 19 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to find out if brain stimulation can help improve sensory integration in children ages 6 to 12 with autism spectrum disorder (ASD). The main questions it aims to answer are:
Does brain stimulation using continuous theta-burst stimulation (cTBS) on bilateral dorsolateral prefrontal cortex (DLPFC) improve how children process sights and sounds together? Can brain functioning, structure, and genetics help predict who responds best to this treatment?
Researchers will compare the results of the randomly assigned active brain stimulation to sham (inactive) stimulation groups to see if the treatment works.
Participants will:
Receive 10 sessions of either active or sham cTBS over 2 weeks Complete a sensory task involving flashes and beeps before and after stimulation Take part in brain scans, namely magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), and provide a saliva sample for genetic testing
Detailed description
This study explores how noninvasive brain stimulation may support children with Autism Spectrum Disorder (ASD) by improving how their brains process and combine sounds and images. It also investigates whether changes in brain function, brain structure, and specific genes can help predict how well a child might respond to this type of stimulation. The study is focused on a core challenge in ASD: differences in how children experience sensory input-especially how their brains process what they see and hear together.
The central concept in this research is something called the Temporal Binding Window (TBW). TBW refers to the brief time window in which the brain naturally fuses sensory information from different senses-like sight and sound-into a single event. For most people, this window is quite narrow: sounds and images that are even slightly out of sync are perceived as separate. But in many children with ASD, this window is wider. That means they may confuse the order or timing of sensory inputs, which can affect communication, behavior, and learning.
To address this, the study uses a method called transcranial magnetic stimulation (TMS). This technique delivers brief, painless pulses of magnetic energy to the surface of the brain using a special coil held against the scalp. The type of TMS used here is called continuous theta burst stimulation (cTBS), which delivers rapid bursts of magnetic pulses designed to gently decrease the excitability of targeted brain areas. In this study, cTBS is used to modulate activity in a region called the dorsolateral prefrontal cortex (DLPFC), which is important for regulating attention, working memory, and sensory control.
A total of 40 children between the ages of 6 and 12 will take part. All participants must have a formal diagnosis of ASD, confirmed using a structured caregiver interview known as the Autism Diagnostic Interview - Revised (ADI-R). They must also demonstrate average or above-average cognitive ability, based on a two-subscale IQ measure from the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V). This ensures that all children can understand the tasks and safely undergo the procedures.
Participants are randomly assigned to one of two groups: an active TMS group or a sham TMS group. In the sham group, the same equipment is used, but no actual magnetic stimulation reaches the brain. This allows researchers to compare outcomes while keeping the children, their families, and the staff unaware of group assignments.
Each child completes ten sessions of either active or sham TMS, over approximately two weeks. The stimulation is applied alternately to the left and right sides of the forehead area, corresponding to the DLPFC. Each session lasts only a few minutes. The stimulation is calibrated individually using a simple test to determine the strength needed to trigger a small movement in the child's hand. All children wear ear protection and are supervised closely by trained staff.
The main outcome of the study is a measure of how well children can process timing between visual and auditory signals. This is assessed using a behavioral task known as the Sound-Induced Flash Illusion (SIFI). In this task, the child looks at a screen and hears beeps while seeing flashes of light. Sometimes there is only one flash, but if it is paired with two quick beeps, some children perceive two flashes instead of one. By changing the timing between the flash and the beeps, researchers can measure the range of delays where the child still experiences the illusion. This range is called the Temporal Binding Window. The wider the window, the more likely the child's brain is to "fuse" signals that actually happened at different times. This task is performed before and after the TMS intervention.
In addition to this behavioral task, the study uses two caregiver questionnaires to track any changes in symptoms:
The Autism Treatment Evaluation Checklist (ATEC) is a brief form filled out by parents. It includes four sections: communication skills, social behavior, sensory awareness, and physical health. It is used to detect broad changes in behavior and well-being.
The Short Sensory Profile (SSP) is another caregiver questionnaire that focuses on how children respond to sensory experiences. It includes questions about sensitivity to touch, sound, movement, and visual stimuli.
These tools are chosen because they are simple, validated, and commonly used in ASD research. They are also sensitive to changes in daily functioning and sensory behavior.
To explore how brain function might change as a result of stimulation, the study uses a technique called functional near-infrared spectroscopy (fNIRS). This is a safe, quiet, and noninvasive method that measures how much oxygen is in the blood within specific brain regions. The child wears a soft cap with small sensors that shine near-infrared light into the scalp. This light reflects back differently depending on how much oxygen is being used in the brain underneath. The sensors are placed over the same area that receives the stimulation (the prefrontal cortex), and the recording is done while the child sits quietly with eyes open. There is no task or performance required-this is simply a measurement of the brain's resting state. Recordings are done once before the stimulation begins and again after the final session.
The study also includes a one-time brain scan using magnetic resonance imaging (MRI). MRI provides a detailed image of the structure of the brain, including its size, shape, and thickness in different regions. This helps researchers look for any physical brain characteristics that might explain differences in sensory processing or predict whether a child will respond to the stimulation. The scan is done in a hospital or imaging center using standard pediatric procedures. Children are given headphones, padding, and visual aids to help them feel comfortable and reduce movement. They do not receive any injections or medications.
Finally, the study includes a one-time saliva collection to analyze DNA. This is done using a small sterile tube into which the child spits or where saliva is collected using a swab. The sample is stored and later processed in a genetics lab. Researchers analyze specific single-nucleotide polymorphisms in genes known to be involved in brain development and sensory processing. These include genes such as SHANK3, CNTNAP2, NRXN1, and SCN2A. The goal is to determine whether certain gene variants are associated with differences in how children respond to the stimulation or process multisensory information. This part of the study is exploratory and does not involve returning results to families.
All procedures are conducted in compliance with safety guidelines for pediatric brain stimulation and neuroimaging. Children are monitored throughout the study, and staff are trained to recognize and manage any discomfort or side effects. The TMS procedures are designed to be brief, well-tolerated, and minimally invasive. Participation is voluntary, and families can withdraw at any time.
This research is part of a broader effort to develop personalized approaches to brain stimulation in children with developmental conditions. By combining behavioral tasks, brain imaging, and genetics, the study aims to understand which children are most likely to benefit from neuromodulation and how their sensory systems can be supported. The long-term goal is to inform clinical interventions that are evidence-based, child-centered, and tailored to individual needs.
This study is conducted at a research site in Almaty, Kazakhstan and is funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan under grant number IRN BR27198099. Ethical approval was obtained from the Local Ethical Committee of Al-Farabi Kazakh National University (Protocol No. IRB-A843). The study does not involve U.S. FDA-regulated products and is not conducted under an IND or IDE.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active cTBS to Bilateral DLPFC | Experimental | Device: Continuous Theta Burst Stimulation to Bilateral DLPFCParticipants receive active continuous theta burst stimulation (cTBS) targeting both the left and right dorsolateral prefrontal cortex (DLPFC) during each session. Stimulation is delivered consecutively to both hemispheres using a standard cTBS protocol: 600 pulses per side (triplet bursts at 50 Hz, repeated at 5 Hz), with each hemisphere receiving stimulation over approximately 40 seconds, at 80% of the individual's active motor threshold. A total of 10 bilateral sessions are delivered over two weeks. |
| Sham cTBS to Bilateral DLPFC | Sham comparator | Device: Sham Continuous Theta Burst StimulationParticipants receive sham stimulation to both the left and right DLPFC during each session. Procedures mimic the active condition, including coil placement, session duration, and auditory cues, but no effective magnetic pulses are delivered. Each participant completes 10 bilateral sham sessions over two weeks. The protocol maintains blinding to control for placebo effects and procedural expectations. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Children aged 6-12 years at the time of enrollment.
- Clinical diagnosis of Autism Spectrum Disorder (ASD) confirmed using the Autism Diagnostic Interview-Revised (ADI-R).
- Intelligence quotient (IQ) ≥ 70 as measured by the General Ability Index (GAI) from the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V).
- Ability to understand and follow simple instructions for behavioral tasks and stimulation procedures.
- Stable medication regimen (if any) for at least 4 weeks before the start of the study.
Key exclusion criteria (8 listed)
- History of epilepsy, seizures, or abnormal EEG suggestive of seizure risk.
- Presence of metal implants, devices, or foreign bodies in or near the head (except dental fillings) that are contraindicated for TMS or MRI.
- Serious neurological disorders other than ASD (e.g., cerebral palsy, brain injury, neurodegenerative disease).
- Severe psychiatric disorders requiring hospitalization or urgent intervention.
- Current or past history of significant head trauma with loss of consciousness > 5 minutes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous Theta Burst Stimulation to Bilateral DLPFCAlso: cTBSParticipants receive continuous theta burst stimulation (cTBS) targeting both the left and right dorsolateral prefrontal cortex (DLPFC) during each session. Each hemisphere is stimulated with 600 pulses (triplets at 50 Hz repeated at 5 Hz) over ~40 seconds, at 80% of the individual's active motor threshold. Sessions are administered once daily over 10 treatment days. | Device | Active cTBS to Bilateral DLPFC |
| Sham Continuous Theta Burst StimulationAlso: Sham cTBSParticipants receive sham continuous theta burst stimulation (cTBS) to both the left and right dorsolateral prefrontal cortex (DLPFC) using a placebo coil that mimics the auditory and tactile sensations of real stimulation but does not produce a magnetic field capable of affecting brain activity. Coil positioning, session timing, and procedure match the active cTBS protocol, including consecutive stimulation to both hemispheres. Both participants and TMS technicians wear earplugs to mask subtle sound differences between active and sham coils. This setup maintains participant and operator blinding and controls for placebo-related effects. | Device | Sham cTBS to Bilateral DLPFC |
Primary outcome
Change in Temporal Binding Window (TBW) Width Measured Using the Sound-Induced Flash Illusion (SIFI) Task
Time frame: Baseline and up to 7 days after the final TMS session.
The TBW reflects the time interval within which auditory and visual stimuli are integrated as a single percept. It is assessed by computing the proportion of illusion-consistent responses across varying stimulus onset asynchronies in the SIFI task. A reduction in TBW width, measured in milliseconds (ms) following stimulation indicates improved multisensory temporal precision.
4 secondary outcomes
Change in Sensory Processing Profile (Short Sensory Profile, SSP)
Time frame: Baseline and up to 7 days after the final TMS session.
Change in Autism Symptom Severity (Autism Treatment Evaluation Checklist, ATEC)
Time frame: Baseline and up to 7 days after the final TMS session.
Change in Resting-State Prefrontal Activity - Mean Oxygenation (fNIRS)
Time frame: Baseline and up to 7 days after the final TMS session.
Change in Resting-State Prefrontal Activity - Functional Connectivity (fNIRS)
Time frame: Baseline and up to 7 days after the final TMS session.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2025.
- Background: PubMed 32869933Siemann JK, Veenstra-VanderWeele J, Wallace MT. Approaches to Understanding Multisensory Dysfunction in Autism Spectrum Disorder. Autism Res. 2020 Sep;13(9):1430-1449. doi: 10.1002/aur.2375. Epub 2020 Sep 1.
- Background: PubMed 25128432Wallace MT, Stevenson RA. The construct of the multisensory temporal binding window and its dysregulation in developmental disabilities. Neuropsychologia. 2014 Nov;64:105-23. doi: 10.1016/j.neuropsychologia.2014.08.005. Epub 2014 Aug 13.
- Background: PubMed 35705542Qiu S, Qiu Y, Li Y, Cong X. Genetics of autism spectrum disorder: an umbrella review of systematic reviews and meta-analyses. Transl Psychiatry. 2022 Jun 15;12(1):249. doi: 10.1038/s41398-022-02009-6.
- Background: PubMed 36441779Camasio A, Panzeri E, Mancuso L, Costa T, Manuello J, Ferraro M, Duca S, Cauda F, Liloia D. Linking neuroanatomical abnormalities in autism spectrum disorder with gene expression of candidate ASD genes: A meta-analytic and network-oriented approach. PLoS One. 2022 Nov 28;17(11):e0277466. doi: 10.1371/journal.pone.0277466. eCollection 2022.
- Background: PubMed 35101065Wang H, Ma ZH, Xu LZ, Yang L, Ji ZZ, Tang XZ, Liu JR, Li X, Cao QJ, Liu J. Developmental brain structural atypicalities in autism: a voxel-based morphometry analysis. Child Adolesc Psychiatry Ment Health. 2022 Jan 31;16(1):7. doi: 10.1186/s13034-022-00443-4.
- Background: PubMed 29892214Sokhadze EM, Lamina EV, Casanova EL, Kelly DP, Opris I, Tasman A, Casanova MF. Exploratory Study of rTMS Neuromodulation Effects on Electrocortical Functional Measures of Performance in an Oddball Test and Behavioral Symptoms in Autism. Front Syst Neurosci. 2018 May 28;12:20. doi: 10.3389/fnsys.2018.00020. eCollection 2018.
- Background: PubMed 32439019Casanova MF, Sokhadze EM, Casanova EL, Opris I, Abujadi C, Marcolin MA, Li X. Translational Neuroscience in Autism: From Neuropathology to Transcranial Magnetic Stimulation Therapies. Psychiatr Clin North Am. 2020 Jun;43(2):229-248. doi: 10.1016/j.psc.2020.02.004. Epub 2020 Apr 8.
- Background: PubMed 20390256Foss-Feig JH, Kwakye LD, Cascio CJ, Burnette CP, Kadivar H, Stone WL, Wallace MT. An extended multisensory temporal binding window in autism spectrum disorders. Exp Brain Res. 2010 Jun;203(2):381-9. doi: 10.1007/s00221-010-2240-4.
- Background: PubMed 19520362Hardan AY, Libove RA, Keshavan MS, Melhem NM, Minshew NJ. A preliminary longitudinal magnetic resonance imaging study of brain volume and cortical thickness in autism. Biol Psychiatry. 2009 Aug 15;66(4):320-6. doi: 10.1016/j.biopsych.2009.04.024. Epub 2009 Jun 11.
- Background: PubMed 30804558Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Baekvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Naerland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnstrom K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Davey Smith G, Stefansson H, Steinberg S, Stevens CR, Sullivan PF, Turley P, Walters GB, Xu X; Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium; BUPGEN; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; 23andMe Research Team; Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Borglum AD. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019 Mar;51(3):431-444. doi: 10.1038/s41588-019-0344-8. Epub 2019 Feb 25.
- Background: PubMed 35562629Gavin N, Hirst RJ, McGovern DP. The magnitude of the sound-induced flash illusion does not increase monotonically as a function of visual stimulus eccentricity. Atten Percept Psychophys. 2022 Jul;84(5):1689-1698. doi: 10.3758/s13414-022-02493-4. Epub 2022 May 13.
- Background: PubMed 25363760De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimaki T, Lin CF, Ma'ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnstrom K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Ruther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK; DDD Study; Homozygosity Mapping Collaborative for Autism; UK10K Consortium; Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 Nov 13;515(7526):209-15. doi: 10.1038/nature13772. Epub 2014 Oct 29.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (IPD), including demographics, baseline and outcome measures from the Sound-Induced Flash Illusion (SIFI) task, Autism Treatment Evaluation Checklist (ATEC), Short Sensory Profile (SSP), genetic markers (saliva DNA sequencing results limited to specified polymorphisms), structural MRI volumetric data, fNIRS prefrontal oxygenation measures, and TMS stimulation parameters, will be shared.
Related trials for Autism Spectrum Disorder (ASD)
Not yet recruiting
"Family Resilience And Mind-body Enhancement" (FRAME): A Randomised Controlled Trial
Autism
Recruiting
Trial of Center-Based vs. In-Home Pivotal Response Treatment (PRT) in Autism
Autism, Autism Spectrum Disorder
Recruiting
Neuroimaging Predictors of Improvement to Pivotal Response Treatment (PRT) in Young Children With Autism
Autism Spectrum Disorder, Autism
RecruitingPhase 2
A Study of Esomeprazole in Children With Autism
Autism, Autism Spectrum Disorder
Recruiting
Transcranial Magnetic Stimulation for Restricted and Repetitive Behavior in ASD
Autism Spectrum Disorder, Autism
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Continuous Theta Burst Stimulation to Bilateral DLPFC in people with Autism Spectrum Disorder (ASD), run by Neurolab Plus at 2 sites in Kazakhstan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 19 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Kazakhstan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Temporal Binding Window (TBW) Width Measured Using the Sound-Induced Flash Illusion (SIFI) Task (time frame: Baseline and up to 7 days after the final TMS session.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07182331, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2025.