Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)

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Brief Title

Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)

Official Title

Longitudinal Study to Identify Early Biomarkers of Autism Spectrum Disorder (ASD) in Infants With Tuberous Sclerosis Complex (TSC)

Brief Summary

      The investigators are enrolling 3-12 month old infants with a diagnosis of tuberous sclerosis
      complex (TSC) for a new study on early markers of autism. The study is looking for early
      signs for autism in a population (TSC) where autism is common. The goal of this project is to
      use behavioral testing, MRI and EEG techniques to identify children at risk for developing
      autism starting at 3 months of age and continuing until 36 months of age. Throughout the
      study, the investigators will recommend Early Intervention services for any child who shows
      early signs of autism.
    

Detailed Description

      This is a five-year multi-site study using MRI and EEG technologies to identify developmental
      precursors of Autism Spectrum Disorder in patients with Tuberous Sclerosis Complex (TSC). The
      study will be enrolling infants at five TSC centers throughout the country, including Boston
      Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Alabama at
      Birmingham, University of Texas at Houston and University of California Los Angeles. The main
      goal of this study is to identify early signs of autism in children with TSC looking at the
      brain through MRI/diffusion tensor imaging, EEG and behavioral/neuropsychological methods.
      Eligible infants between the ages of 3-12 months will be evaluated longitudinally at regular
      visit intervals up to 3 years of age.

      Study Objectives

        1. To characterize the developmental precursors of ASD in a large number of TSC infants
           using a prospective multi-center design: Infants with TSC will be evaluated
           longitudinally at ages 3, 6, 9, 12, 18, 24 and 36 months. At each age, children will
           undergo standardized evaluations, using cognitive and adaptive measures. At age 24 and
           36 months, formal assessment for autism will be performed. Clinical data including
           medication use, seizure history, EEG activity, genotypic variation, and co-morbidities
           will be recorded to determine if specific clinical factors modify the course of
           development.

        2. To identify biomarkers with advanced diffusion tensor imaging (DTI) that help predict
           development of ASD in TSC infants: The investigators hypothesize that decreased white
           matter integrity performed annually for each of the first 3 years of life, including DTI
           sequences with tractography. Radial, axial, and mean diffusivity and fractional
           anisometry will be calculated for each time point and change over time correlated with
           development of ASD to determine relative risk. Individual measures at each time point
           will be compared between ASD and non-spectrum groups to assess the individual impact of
           each measure and timing.

        3. To identify biomarkers with quantitative EEG that help predict development of ASD in TSC
           infants: The investigators hypothesize that altered functional connectivity, as measured
           by qEEG coherence and high frequency oscillations, will correlate with development of
           ASD in TSC. Quantitative EEG (qEEG), EEG coherence/gamma frequency (30-50Hz), and high
           frequency oscillations encompassing both ripples (80-250H) and fast ripples (250-500 Hz)
           will be measured at each time point. Changes over time will be correlated with
           development of ASD to determine relative risk, as will comparison of individual measures
           between the two groups. EEG findings will also be correlated with MR results obtained to
           further couple functional connectivity as measured by EEG with structural connectivity
           measured by DTI.
    


Study Type

Observational


Primary Outcome

ADOS evaluation score at the 36 month visit


Condition

Tuberous Sclerosis Complex


Study Arms / Comparison Groups

 Tuberous Sclerosis Complex (TSC)
Description:  Tuberous Sclerosis Complex

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

166

Start Date

January 2013

Completion Date

December 2020

Primary Completion Date

December 2019

Eligibility Criteria

        Inclusion Criteria:

          1. Meets genetic or clinical diagnostic criteria for TSC (Tuberous Sclerosis), the latter
             based on current recommendations for diagnostic evaluation, such as physical exam,
             neuroimaging, echocardiogram.

          2. Age criteria: 3 months- 12 months of age at time of enrollment. For study purposes, 3
             months is defined as ≥ 9 weeks, 1 day and 12 months is defined as ≤ 13.5 months.

        Exclusion Criteria:

          1. Prematurity, defined as gestational age < 36 weeks at time of delivery

          2. Has taken an investigational drug as part of another research study, within 30 days
             prior to study enrollment

          3. Is taking an mTOR inhibitor such as rapamycin, sirolimus, or everolimus (other than
             topical formulations) at the time of study enrollment

          4. Subependymal Giant Cell Astrocytoma requiring medical or surgical treatment at the
             time of study enrollment

          5. History of epilepsy surgery at the time of study enrollment

          6. Contraindications to MRI scanning, such as metal implants/non-compatible medical
             devices or medical conditions
      

Gender

All

Ages

3 Months - 12 Months

Accepts Healthy Volunteers

No

Contacts

Mustafa Sahin, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01780441

Organization ID

IRB-P00005074

Secondary IDs

1U01NS082320-01

Responsible Party

Principal Investigator

Study Sponsor

Boston Children's Hospital

Collaborators

 National Institute of Neurological Disorders and Stroke (NINDS)

Study Sponsor

Mustafa Sahin, MD, PhD, Principal Investigator, Boston Children's Hospital


Verification Date

February 2021