Clinical trial NCT02836405: TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders
Official title: Investigations of Neuroplasticity Mechanisms in Autism Spectrum Disorders
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Autism Spectrum Disorder
Intellectual Disability
Keywords: Autism
ASD
Autistic Disorder
Pervasive Development Disorders
Pervasive Child Development Disorders
Asperger's Syndrome
Transcranial Magnetic Stimulation
TMS
Autism Spectrum Disorder
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: National Institute of Mental Health (NIMH)
First posted: 2016-07-19
Enrollment: 164
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adults diagnosed with an Autism Spectrum Disorder (ASD), as well as controls.

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.

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.

Eligibility 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.

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.

Primary outcomes:
measure: Percent of baseline TMS-induced measures of human synaptic plasticity
timeFrame: 120 minutes after cTBS
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Alexander Rotenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center
name: Alvaro Pascual-Leone, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: