Clinical trial NCT02461459: Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
Official title: Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Tuberous Sclerosis
Autism Disorder
Intellectual Disability
Keywords: Tuberous Sclerosis Complex
TSC
Autism
ASD
Intellectual Disability
ID
MRI
EEG
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Tuberous Sclerosis Alliance
name: National Center for Advancing Translational Sciences (NCATS)
name: Office of Rare Diseases (ORD)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-06-03
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: A total of 195 participants over the age of 18 months old with TSC and suspected or diagnosed ASD, ID, or combined ASD/ID will be enrolled into the study. Diagnosis of TSC will be based on established clinical or genetic criteria. Subjects will be enrolled from current and new TSC patients at each of the 6 centers.

Brief summary: The purpose of this study is to characterize the developmental phenotype of ASD and ID and to identify biomarkers using advanced MRI methodology and electrophysiological biomarkers of synaptic function and connectivity predictive of ASD and ID presence and severity in patients with TSC. In addition, this study will be establishing infrastructure for the collection and storage of human bio-specimens, including genetic material, from TSC patients and their family members with ASD.

Detailed description: Tuberous Sclerosis Complex (TSC) is a multi-system disease that usually exhibits a high variability in clinical findings both among and within families. About 50% of individuals with TSC develop intellectual disability (ID) and/or autism spectrum disorder (ASD). The purpose of this research study is to learn more information about ASD/ID in individuals with TSC through neurobehavioral assessments, electroencephalogram (EEG) data, and magnetic resonance imaging so that ultimately effective treatments and interventions for ASD/ID can be realized.

Individuals with TSC will be asked to participate in this study if they are 18 months or older at the time of enrollment and have been diagnosed with suspected or confirmed autism spectrum disorder and/or intellectual disability, as well as healthy controls. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. The participant and at least one biological parent will be asked to provide biological specimens including DNA and RNA for inclusion in the TSC RDCRN Biorepository.

The study involves 3 on site visits over the course of two years. Study visits will vary in length from about 4 hours to 6 hours. Study visits involve a physical exam, medical history questions, and neuropsychological assessments. A subset of participants between the ages of 2 and 11 years old will take part in the EEG portion of the study. At one point during the study, a blood draw will be done for future research studies. Individuals who have a clinically indicated MRI will have an option to provide routine clinical scans for analysis.

Eligibility criteria: Inclusion Criteria:

* Meets genetic or clinical diagnostic criteria for TSC (Tuberous Sclerosis), the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, and echocardiogram.
* Age criteria: over 18 months of age at time of enrollment.
* Is diagnosed or suspected to have ASD and/or ID.
* Primary communicative language is English

Exclusion Criteria:

* Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment.
* For subjects involved in imaging biomarker assessment: contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator.
* For subjects involved in EEG/ERP biomarker assessment: contraindications to EEG/ERP, such as uncooperative or destructive behaviors preventing lead placement or capture by ERP/VEP equipment. Under age 2 or above age 11 at the time of enrollment.
* Unwilling or unable to comply with study procedures and assessments.

Primary outcomes:
measure: Change in ADOS-2 scores at end of study
timeFrame: 24 months
measure: Change in SBIS-5 scores or Mullen Scales of Early Learning (MSEL) at end of study
timeFrame: 24 months
measure: Change in Fractional anisotropy (FA) at 12 months
timeFrame: 12 months
measure: Change in fractional anisotropy (FA) at 24 months
timeFrame: 24 months
measure: Change in radial diffusivity (RD) at 12 months
timeFrame: 12 months
measure: Change in radial diffusivity (RD) at 24 months
timeFrame: 24 months
measure: Change in mean diffusivity (MD) of cerebellar fascicles at 12 months
timeFrame: 12 months
measure: Change in mean diffusivity (MD) of cerebellar fascicles at 24 months
timeFrame: 24 months
measure: Change in axial diffusivity (AD) at 12 months
timeFrame: 12 months
measure: Change in axial diffusivity (AD) at 24 months
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: University of Texas at Houston
state: Texas
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Darcy Krueger, MD, PhD
role: STUDY_CHAIR
References: