Investigation of Brain Plasticity in Autism Spectrum Disorders

NCT ID: NCT04706364

Last Updated: 2021-11-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-10

Study Completion Date

2022-05-31

Brief Summary

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Individuals with autism spectrum disorders (ASD) commonly experience variances in tactile behaviors, such as hypersensitivity to light touch stimuli, altered texture discrimination, and hyporesponsivity to pain. Researchers aim to investigate the somatosensory sensitivity and sensorimotor integration utilizing novel, objective behavioral assays and TMS. The main purpose is to study brain plasticity (the changes that occur in the brain through experience) in individuals with autism spectrum disorders.

Detailed Description

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Individuals with autism spectrum disorders (ASD) commonly experience variances in tactile behaviors, such as hypersensitivity to light touch stimuli, altered texture discrimination and hyporesponsivity to pain. The degree of this somatosensory impairment correlates with increased anxiety behaviors as well as impairments in social behavior among ASD patients.

There remains an unmet need for suppressing the tactile hypersensitivity, which may improve anxiety and other core symptoms of ASD; however, methodologies for measuring tactile sensitivity vary widely across clinical and basic research fields. There is an urgent need for direct and objective sensory reactivity metrics in clinical studies to assess deficits in specific patient populations and for designing effective therapeutic strategies. As compared with traditional behavioral methods, the investigators propose to test novel, objective and quantitative metrics of somatosensory sensitivity in individuals with ASD.

In addition, transcranial magnetic stimulation (TMS) provides a method of measuring cortical reactivity offering the advantage of providing behaviorally independent results that are largely unaffected by attention or cognitive ability. Therefore, a TMS-based physiologic biomarker may be applicable to all individuals across the autism spectrum. A form of TMS known as paired associative stimulation (PAS) can be used to study the suggested impairment in integration of sensory input into cortical function that underlies tactile hypersensitivity in ASD. Thus, the investigators aim to investigate somatosensory sensitivity and sensorimotor integration utilizing novel, objective behavioral assays and TMS.

Participation in the study will consist of up to seven visits: one screening visit, two sensory testing visits, and two - four TMS sessions. The screening visit is expected to last between 2-3 hours, during which participants will first provide informed consent. Participants will then receive a thorough medical examination by a neurologist, and a neuropsychological evaluation (including IQ measures and ASD specific evaluations). If eligible to continue, participants will then come back for two sensory visits and two - four TMS visits that are spaced a minimum of 1 week apart.

Conditions

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Autism Spectrum Disorder

Study Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Autism Spectrum Disorder (ASD)

Individuals diagnosed with an Autism Spectrum Disorder

Neuropsychological Testing

Intervention Type BEHAVIORAL

Includes an IQ test, Autism Diagnostic Observation Schedule-2 (ADOS-2), and Autism Diagnostic Interview-Revised (ADI-R) assessments.

(Optional) Saliva Collection

Intervention Type GENETIC

The sample is to test for genes (BDNF/APOE/COMT) that everyone has, but people have different varieties of these genes.

Genetic testing is funded by Boston Children's Hospital.

Sensory Testing

Intervention Type DEVICE

Three different tests will be completed:

the tactile prepulse inhibition test (PPI) texture perception indentation testing (Mechanical Detection Threshold).

Investigators will also apply mild electrical stimulation to the median nerve of the hand (on the wrist).

The second sensory visit will be another version of the PPI testing involving hearing and sound.

Electroencephalogram (EEG)

Intervention Type DEVICE

A cap will be placed on the participants head that will be filled with electrodes (small discs). The EEG will allow investigators to measure how the brain reacts to the sensory testing.

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Single pulses of TMS, as well as PAS (a second type of TMS), will be applied to the cortex.

There will be two - four identical TMS testing visits.

Healthy Control

Typically developing individuals without a history of autism

Neuropsychological Testing

Intervention Type BEHAVIORAL

Includes an IQ test, Autism Diagnostic Observation Schedule-2 (ADOS-2), and Autism Diagnostic Interview-Revised (ADI-R) assessments.

(Optional) Saliva Collection

Intervention Type GENETIC

The sample is to test for genes (BDNF/APOE/COMT) that everyone has, but people have different varieties of these genes.

Genetic testing is funded by Boston Children's Hospital.

Sensory Testing

Intervention Type DEVICE

Three different tests will be completed:

the tactile prepulse inhibition test (PPI) texture perception indentation testing (Mechanical Detection Threshold).

Investigators will also apply mild electrical stimulation to the median nerve of the hand (on the wrist).

The second sensory visit will be another version of the PPI testing involving hearing and sound.

Electroencephalogram (EEG)

Intervention Type DEVICE

A cap will be placed on the participants head that will be filled with electrodes (small discs). The EEG will allow investigators to measure how the brain reacts to the sensory testing.

Transcranial Magnetic Stimulation

Intervention Type DEVICE

Single pulses of TMS, as well as PAS (a second type of TMS), will be applied to the cortex.

There will be two - four identical TMS testing visits.

Interventions

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Neuropsychological Testing

Includes an IQ test, Autism Diagnostic Observation Schedule-2 (ADOS-2), and Autism Diagnostic Interview-Revised (ADI-R) assessments.

Intervention Type BEHAVIORAL

(Optional) Saliva Collection

The sample is to test for genes (BDNF/APOE/COMT) that everyone has, but people have different varieties of these genes.

Genetic testing is funded by Boston Children's Hospital.

Intervention Type GENETIC

Sensory Testing

Three different tests will be completed:

the tactile prepulse inhibition test (PPI) texture perception indentation testing (Mechanical Detection Threshold).

Investigators will also apply mild electrical stimulation to the median nerve of the hand (on the wrist).

The second sensory visit will be another version of the PPI testing involving hearing and sound.

Intervention Type DEVICE

Electroencephalogram (EEG)

A cap will be placed on the participants head that will be filled with electrodes (small discs). The EEG will allow investigators to measure how the brain reacts to the sensory testing.

Intervention Type DEVICE

Transcranial Magnetic Stimulation

Single pulses of TMS, as well as PAS (a second type of TMS), will be applied to the cortex.

There will be two - four identical TMS testing visits.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* For ASD group:

* Clinical diagnosis of a disorder on the autism spectrum according to:

1. DSM-IV or DSM 5 criteria
2. IQ\>70 (as determined by the Abbreviated Stanford-Binet IQ)
* For the Control group:

* No history of ASD or other developmental delay
* No history of ASD or other developmental delay in first-degree relatives.
* No history of clinical diagnosis of an anxiety disorder

Exclusion Criteria

* Both ASD and Control groups:

* Intracranial pathology, cerebral palsy, history of severe head injury, or syndromic dysmorphology
* History of fainting spells of unknown or undetermined etiology that might constitute seizure
* History of seizure or epilepsy
* Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency
* Metal implants (excluding dental fillings) or devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible MD
* Substance abuse or dependence within the past six months
* Chronic treatment with prescription medications that decrease cortical seizure threshold
* Peripheral neuropathy, as determined by the study MD during neurologic exam
* For the Control group:

* For control participants' medical history will be reviewed for diagnoses of neurologic or psychiatric disease. If in the judgment of the investigator, the condition, e.g., depression, is well-controlled with stable medications, and does not include abnormalities of the sensory motor systems, they may be included in the study. Control participants will be excluded from taking part in the study if they have a 1st degree relative with ASD.
Minimum Eligible Age

6 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Simons Foundation Autism Research Initiative (SFARI)

UNKNOWN

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Alexander Rotenberg

Associate Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexander Rotenberg, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

[email protected]

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Paul MacMullin

Role: CONTACT

Phone: 617-355-4875

Email: [email protected]

Facility Contacts

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Paul MacMullin

Role: primary

Other Identifiers

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R21MH120438

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-P00027556

Identifier Type: -

Identifier Source: org_study_id