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

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ClinicalTrials.gov Identifier: NCT02461459
Recruitment Status : Recruiting
First Posted : June 3, 2015
Last Update Posted : April 7, 2020
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Tuberous Sclerosis Alliance
National Center for Advancing Translational Science (NCATS)
Office of Rare Diseases (ORD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Mustafa Sahin, Boston Children’s Hospital

Tracking Information
First Submitted Date May 11, 2015
First Posted Date June 3, 2015
Last Update Posted Date April 7, 2020
Study Start Date May 2015
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 3, 2020)
  • Change in ADOS-2 scores at end of study [ Time Frame: 24 months ]
    Using standardized composite score for ADOS-2 performed yearly to determine ASD
  • Change in SBIS-5 scores or Mullen Scales of Early Learning (MSEL) at end of study [ Time Frame: 24 months ]
    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
  • Change in Fractional anisotropy (FA) at 12 months [ Time Frame: 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,
  • Change in fractional anisotropy (FA) at 24 months [ Time Frame: 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
  • Change in radial diffusivity (RD) at 12 months [ Time Frame: 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
  • Change in radial diffusivity (RD) at 24 months [ Time Frame: 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
  • Change in mean diffusivity (MD) of cerebellar fascicles at 12 months [ Time Frame: 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
  • Change in mean diffusivity (MD) of cerebellar fascicles at 24 months [ Time Frame: 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
  • Change in axial diffusivity (AD) at 12 months [ Time Frame: 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
  • Change in axial diffusivity (AD) at 24 months [ Time Frame: 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
Original Primary Outcome Measures
 (submitted: June 1, 2015)
  • Change in ADOS-2 at 12 months [ Time Frame: 12 months ]
    Using standardized composite score for ADOS-2 performed at 12 months to determine ASD
  • Change in SBIS-5 at 12 months [ Time Frame: 12 months ]
    Using standardized IQ score from the Stanford-Binet Intelligence Scales Fifth Edition (SBIS-5) performed at 12 months to determine ID
  • Change in Fractional anisotropy (FA) at 12 months [ Time Frame: 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,
  • Change in ADOS-2 at 24 months [ Time Frame: 24 months ]
    Using standardized composite score for ADOS-2 performed at 24 months to determine ASD
  • Change in SBIS-5 at 24 months [ Time Frame: 24 months ]
    Using standardized IQ score from the Stanford-Binet Intelligence Scales Fifth Edition (SBIS-5) performed at 12 months to determine ID
  • Change in radial diffusivity (RD) at 12 months [ Time Frame: 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
  • Change in fractional anisotropy (FA) at 24 months [ Time Frame: 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
  • Change in axial diffusivity (AD) at 12 months [ Time Frame: 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
  • Change in mean diffusivity (MD) of cerebellar fascicles at 12 months [ Time Frame: 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
  • Change in radial diffusivity (RD) at 24 months [ Time Frame: 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
  • Change in axial diffusivity (AD) at 24 months [ Time Frame: 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
  • Change in mean diffusivity (MD) of cerebellar fascicles at 24 months [ Time Frame: 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
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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)
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Blood draw for future correlative studies in the TSC Biorepository of the Developmental Synaptopathies Consortium.
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.
Condition
  • Tuberous Sclerosis
  • Autism Disorder
  • Intellectual Disability
Intervention Not Provided
Study Groups/Cohorts Tuberous Sclerosis Complex
Tuberous Sclerosis Complex
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 3, 2020)
195
Original Estimated Enrollment
 (submitted: June 1, 2015)
100
Estimated Study Completion Date December 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: Rajna Filip-Dhima, MS 617-919-7068 Rajna.Filip-Dhima@childrens.harvard.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02461459
Other Study ID Numbers IRB-P00013585
1U54NS092090 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Mustafa Sahin, Boston Children’s Hospital
Study Sponsor Boston Children’s Hospital
Collaborators
  • National Institutes of Health (NIH)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Tuberous Sclerosis Alliance
  • National Center for Advancing Translational Science (NCATS)
  • Office of Rare Diseases (ORD)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Study Chair: Darcy Krueger, MD, PhD Children's Hospital Medical Center, Cincinnati
PRS Account Boston Children’s Hospital
Verification Date April 2020