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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

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.

Condition or disease
Tuberous Sclerosis Autism Disorder Intellectual Disability

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.

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Study Type : Observational
Estimated Enrollment : 195 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
Study Start Date : May 2015
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025


Group/Cohort
Tuberous Sclerosis Complex
Tuberous Sclerosis Complex



Primary Outcome Measures :
  1. 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

  2. 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

  3. 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,

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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


Biospecimen Retention:   Samples With DNA
Blood draw for future correlative studies in the TSC Biorepository of the Developmental Synaptopathies Consortium.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02461459


Contacts
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Contact: Rajna Filip-Dhima, MS 617-919-7068 Rajna.Filip-Dhima@childrens.harvard.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jessica Krefting, RN    205-975-2890    JessicaKrefting@uab.edu   
Contact    256-533-0833      
Principal Investigator: Martina Bebin, MD         
United States, California
University of California at Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Carly Hyde    310-825-8738    CHyde@mednet.ucla.edu   
Principal Investigator: Shafali Jeste, MD         
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Swetapadma Patnaik    650-721-1458    sweta@stanford.edu   
Principal Investigator: Brenda Porter, MD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Amy Mason    617-919-3499    Amy.Mason@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Molly Griffith    513-636-9669    Molly.Griffith@cchmc.org   
Principal Investigator: Darcy Krueger, MD, PhD         
United States, Texas
University of Texas at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Elida Salazar    713-500-5766    Elida.L.Salazar@uth.tmc.edu   
Principal Investigator: Hope Northrup, MD         
Sponsors and Collaborators
Boston Children’s Hospital
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
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Study Chair: Darcy Krueger, MD, PhD Children's Hospital Medical Center, Cincinnati
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Responsible Party: Mustafa Sahin, Assistant in NeurologyAssociate Professor of Neurology, Harvard Medical School, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02461459    
Other Study ID Numbers: IRB-P00013585
1U54NS092090 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: April 7, 2020
Last Verified: April 2020
Keywords provided by Mustafa Sahin, Boston Children’s Hospital:
Tuberous Sclerosis Complex
TSC
Autism
ASD
Intellectual Disability
ID
MRI
EEG
Additional relevant MeSH terms:
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Tuberous Sclerosis
Intellectual Disability
Sclerosis
Autistic Disorder
Autism Spectrum Disorder
Pathologic Processes
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn