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

NCT02461459 | Active Not Recruiting DMC

• 2 other identifiers: IRB-P000135851U54NS092090
• Study Type: observational
• Target: 205
• Locations: 1 country
• Sites: 6

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.

Conditions

Tuberous Sclerosis; Autism Disorder; Intellectual Disability

Keywords

Tuberous Sclerosis Complex; TSC; Autism; ASD; Intellectual Disability; ID; MRI; EEG

Outcome Measures

Primary Outcomes (10)

• Change in ADOS-2 scores at end of study

  Using standardized composite score for ADOS-2 performed yearly to determine ASD

  24 months

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Study Arms (1)

Tuberous Sclerosis Complex

Tuberous Sclerosis Complex

Eligibility Criteria

• Age: 18 Months+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University of Texas at Houston

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood draw for future correlative studies in the TSC Biorepository of the Developmental Synaptopathies Consortium.

MeSH Terms

Conditions

Tuberous Sclerosis; Autistic Disorder; Intellectual Disability

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Darcy Krueger, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology, Harvard Medical School

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: June 3, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 26, 2024

Record last verified: 2024-10

Locations

US (6)