Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)
|ClinicalTrials.gov Identifier: NCT01780441|
Recruitment Status : Active, not recruiting
First Posted : January 31, 2013
Last Update Posted : February 7, 2018
|Condition or disease|
|Tuberous Sclerosis Complex|
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.
- 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.
- 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.
- 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|
|Actual Enrollment :||166 participants|
|Official Title:||Longitudinal Study to Identify Early Biomarkers of Autism Spectrum Disorder (ASD) in Infants With Tuberous Sclerosis Complex (TSC)|
|Actual Study Start Date :||January 2013|
|Estimated Primary Completion Date :||February 2019|
|Estimated Study Completion Date :||December 2019|
U.S. FDA Resources
Tuberous Sclerosis Complex (TSC)
Tuberous Sclerosis Complex
- ADOS evaluation score at the 36 month visit [ Time Frame: 36 months ]The ADOS performed at 24 and 36 months will be used as a preliminary diagnosis for data analysis. The primary outcome is the possible clinical diagnosis of autism spectrum disorder per the DSM 5 guidelines (Autistic Disorder, Asperger's and PDD-NOS).
- MRI biomarkers [ Time Frame: 36 months ]MRI biomarkers obtained at baseline, 12, 24, 36 months will be applied to characterize individual patients in terms of brain tissue, white matter structure and connectivity, functional networks, and pathology. Brain tissue segmentation will be based on structural images derived from T1- and T2-weighted and FLAIR sequences using automated software tools designed for these tasks. White matter integrity and organization will be inferred from DTI imaging sequences. Structural connectivity networks will be delineated by DTI tractography assessment.
- EEG biomarkers [ Time Frame: 36 months ]One-hour video-EEG containing both wakefulness and sleep (minimum of 20 minutes of each) will be obtained at baseline, 3, 6, 9, 12, 18, 24 and 36 months. Functional connectivity and pathological activity will be determined by measurement of EEG coherence and gamma frequency/high frequency oscillations.
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01780441
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, California|
|University of California at Los Angeles|
|Los Angeles, California, United States, 90095|
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Ohio|
|Cincinnati Children's Hospital|
|Cincinnati, Ohio, United States, 45229|
|United States, Texas|
|University of Texas at Houston|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Mustafa Sahin, MD, PhD||Boston Children’s Hospital|
|Principal Investigator:||Darcy Krueger, MD, PhD||Children's Hospital Medical Center, Cincinnati|