Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)

Intellectual Disability Clinical Trial

Official title:

Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02461459
• Other study ID #: IRB-P00013585
• Secondary ID: 1U54NS092090
• Status: Recruiting
• Start date: May 2015
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: Boston Children's Hospital
• Contact: Rajna Filip-Dhima, MS
• Phone: 617-919-7068
• Email: Rajna.Filip-Dhima[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 195
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Autism Disorder
• Autism Spectrum Disorder
• Autistic Disorder
• Intellectual Disability
• Sclerosis
• Tuberous Sclerosis

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Texas at Houston	Houston	Texas
United States	University of California at Los Angeles	Los Angeles	California
United States	Stanford University	Palo Alto	California

Sponsors (7)

Lead Sponsor	Collaborator
Boston Children's Hospital	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Office of Rare Diseases (ORD), Tuberous Sclerosis Alliance

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in ADOS-2 scores at end of study	Using standardized composite score for ADOS-2 performed yearly to determine ASD	24 months
Primary	Change in SBIS-5 scores or Mullen Scales of Early Learning (MSEL) at end of study	Using standardized IQ score from the Stanford-Binet Intelligence Scales Fifth Edition (SBIS-5) or Mullen Scales of Early Learning (MSEL) performed yearly to determine ID	24 months
Primary	Change in Fractional anisotropy (FA) at 12 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be fractional anisotropy (FA) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) of cerebellar fascicles corresponding to the neuroanatomically-defined excitatory and inhibitory projections cerebellar Purkinje neurons,	12 months
Primary	Change in fractional anisotropy (FA) at 24 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be fractional anisotropy (FA) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months	24 months
Primary	Change in radial diffusivity (RD) at 12 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be radial diffusivity (RD) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months	12 months
Primary	Change in radial diffusivity (RD) at 24 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be radial diffusivity (RD) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months	24 months
Primary	Change in mean diffusivity (MD) of cerebellar fascicles at 12 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be mean diffusivity (MD) of cerebellar fascicles determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months	12 months
Primary	Change in mean diffusivity (MD) of cerebellar fascicles at 24 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be mean diffusivity (MD) of cerebellar fascicles determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months	24 months
Primary	Change in axial diffusivity (AD) at 12 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be axial diffusivity (AD) determined by MRI diffusion tensor imaging (DTI) with tractography at 12 months	12 months
Primary	Change in axial diffusivity (AD) at 24 months	To determine cerebellum white matter structural integrity, the primary outcome measures will be axial diffusivity (AD) determined by MRI diffusion tensor imaging (DTI) with tractography at 24 months	24 months