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TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders

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ClinicalTrials.gov Identifier: NCT02836405
Recruitment Status : Recruiting
First Posted : July 19, 2016
Last Update Posted : October 5, 2017
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Alexander Rotenberg, Boston Children’s Hospital

Brief Summary:
The main purpose is to study brain plasticity (the changes that occur in the brain through experience) in individuals with autism spectrum disorder (ASD). Research suggests that during development, the brains of individuals with ASD may change in response to their experiences differently than the brains of typically developing individuals. Investigators want to understand why and how this difference may contribute to the symptoms of ASD.

Condition or disease Intervention/treatment
Autism Spectrum Disorder Intellectual Disability Device: Transcranial Magnetic Stimulation

Detailed Description:

Autism Spectrum Disorders (ASD) are diagnosed clinically, based on key symptoms. As ASD phenotypic variability is large, and symptoms can manifest at different ages and degrees, the clinical diagnosis is challenging. To date, there remains an unmet need for a valid and reliable endophenotype that would facilitate ASD diagnosis early in life, enable efficient study of ASD risk factors, and eventually serve as a useful biomarker to inform the development of effective therapies and assess treatment response in future clinical trials.

As compared with behavioral or neuroimaging methods, transcranial magnetic stimulation (TMS) offers the advantage of providing behaviorally independent results that are largely unaffected by attention or cognitive ability. Therefore, a TMS based endophenotype may be applicable to all individuals across the autism spectrum.

At Boston Children's Hospital, each subject's participation in the study will consist of four visits: two screening visits, and two TMS sessions. At Beth Israel Deaconess Medical Center, each subject's participation will consist of three visits: one screening visit, and two TMS sessions. Each 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 identical TMS visits, that are spaced 1-5 weeks apart. These visits are expected to last between 3-4 hours, and include the TMS measures of brain plasticity.


Study Type : Observational
Estimated Enrollment : 185 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Investigations of Neuroplasticity Mechanisms in Autism Spectrum Disorders
Study Start Date : May 2015
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019


Group/Cohort Intervention/treatment
Autism Spectrum Disorder (ASD)
Individuals diagnosed with an Autism Spectrum Disorder (ASD) will receive transcranial magnetic stimulation (TMS) to measure brain plasticity.
Device: Transcranial Magnetic Stimulation
Single pulses of TMS as well as continuous theta burst stimulation (cTBS) will be applied to the motor cortex.

Intellectual Disability
Individuals diagnosed with an intellectual disability will receive transcranial magnetic stimulation (TMS) to measure brain plasticity.
Device: Transcranial Magnetic Stimulation
Single pulses of TMS as well as continuous theta burst stimulation (cTBS) will be applied to the motor cortex.

Healthy Control
Typically developing individuals without a history of autism will receive transcranial magnetic stimulation (TMS) to measure brain plasticity.
Device: Transcranial Magnetic Stimulation
Single pulses of TMS as well as continuous theta burst stimulation (cTBS) will be applied to the motor cortex.




Primary Outcome Measures :
  1. Percent of baseline TMS-induced measures of human synaptic plasticity [ Time Frame: 120 minutes after cTBS ]
    Synaptic plasticity will be measured using the MEPs in response to cTBS. Baseline MEPs will be calculated before cTBS, and at different time points following cTBS up to 120 minutes. The investigators will compare post-cTBS MEPs to the baseline MEPs to calculate the percent change from baseline.


Biospecimen Retention:   Samples With DNA
Saliva sample for genetic testing (optional)


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Ages Eligible for Study:   6 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Children and adults diagnosed with an Autism Spectrum Disorder (ASD), as well as controls.
Criteria

Inclusion Criteria at Boston Children's Hospital (children):

  • For ASD group:

    1. Clinical diagnosis of a disorder on the autism spectrum.
    2. Assessment using the Autism Diagnostic Observation Schedule.
    3. Assessment using the Autism Diagnostic Interview-Revised.
    4. Children ages 6-16.
    5. IQ>70.
    6. Verbal.

Inclusion Criteria at Beth Israel Deaconess Medical Center (adults):

  • For ASD group:

    1. Clinical diagnosis of a disorder on the autism spectrum.
    2. Assessment using the Autism Diagnostic Observation Schedule.
    3. Adults ages 21-65.
  • For the group of individuals with Intellectual Disability:

    1. Mild to moderate intellectual disability.
    2. No history of ASD.
    3. Adults ages 21-65.
    4. IQ<70.

Exclusion Criteria:

  • Intracranial pathology, cerebral palsy, history of severe head injury, significant dysmorphology, or known intracranial lesion.
  • History of fainting spells of unknown or undetermined etiology.
  • History of head injury resulting in prolonged loss of consciousness.
  • History of seizures, diagnosis of epilepsy, or immediate family history of epilepsy.
  • Any progressive neurological disorder or signs of intracranial pressure.
  • Chronic uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure.
  • Metal implants or devices.
  • Substance abuse or dependence within the past six months.
  • Certain prescription medications that decrease cortical seizure threshold.
  • Pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02836405


Contacts
Contact: Mary Ryan, MS 617-667-0206 Mary.Ryan@childrens.harvard.edu

Locations
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mary Ryan, MS    617-667-0206    Mary.Ryan@childrens.harvard.edu   
Sub-Investigator: Alvaro Pascual-Leone, MD, PhD         
Principal Investigator: Alexander Rotenberg, MD, PhD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mary Ryan, MS    617-667-0206    mryan12@bidmc.harvard.edu   
Principal Investigator: Alvaro Pascual-Leone, MD, PhD         
Sub-Investigator: Alexander Rotenberg, MD, PhD         
Sponsors and Collaborators
Boston Children’s Hospital
Beth Israel Deaconess Medical Center
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Alexander Rotenberg, MD, PhD Boston Children’s Hospital
Principal Investigator: Alvaro Pascual-Leone, MD, PhD Beth Israel Deaconess Medical Center

Responsible Party: Alexander Rotenberg, Associate Professor of Neurology, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02836405     History of Changes
Other Study ID Numbers: 00014965
1R01MH100186-01A1 ( U.S. NIH Grant/Contract )
First Posted: July 19, 2016    Key Record Dates
Last Update Posted: October 5, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plasticity data will be reported to subjects by the PI.

Keywords provided by Alexander Rotenberg, Boston Children’s Hospital:
Autism
ASD
Autistic Disorder
Pervasive Development Disorders
Pervasive Child Development Disorders
Asperger's Syndrome
Transcranial Magnetic Stimulation
TMS
Autism Spectrum Disorder

Additional relevant MeSH terms:
Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Nervous System Diseases
Intellectual Disability
Pathologic Processes
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms