Clinical trial NCT04706364: Investigation of Brain Plasticity in Autism Spectrum Disorders
Official title: Investigations of Sensorimotor Plasticity in Autism Spectrum Disorders
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Autism Spectrum Disorder
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Simons Foundation Autism Research Initiative (SFARI)
First posted: 2021-01-12
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children diagnosed with an Autism Spectrum Disorder (ASD), as well as controls.

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Textured novel object recognition test (NORT) and mechanical detection threshold (MDT) with von Frey hairs
timeFrame: 3 years
measure: Somatosensory temporal discrimination threshold (STDT) and PAS-induced modulation of motor-evoked potentials (MEPs)
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Alexander.Rotenberg@childrens.harvard.edu
name: Alexander Rotenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: