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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 : Active, not recruiting
First Posted : June 3, 2015
Last Update Posted : October 2, 2018
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)
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 identify biomarkers using advanced MRI methodology predictive of ASD and ID presence and severity in pediatric 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 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 between the ages of 3 and 21 years old and have been diagnosed with suspected or confirmed autism spectrum disorder and/or intellectual disability. Both males and females will be asked to participate. Additionally, to be eligible for study participation, individuals' primary communicative language must be English. Also, 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 5 visits (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. Blood will be drawn during the baseline visit for DNA and RNA studies. Individuals with TSC have annual MRI scans as clinically indicated. The clinical scan will be extended for 15 minutes as part of this study.


Study Type : Observational
Estimated Enrollment : 105 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 2019
Estimated Study Completion Date : December 2019


Group/Cohort
Tuberous Sclerosis Complex
Tuberous Sclerosis Complex



Primary Outcome Measures :
  1. 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

  2. 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

  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 ADOS-2 at 24 months [ Time Frame: 24 months ]
    Using standardized composite score for ADOS-2 performed at 24 months to determine ASD

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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


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

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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
A total of 105 children between the ages of 3-21 years 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. Twenty (20) subjects will be enrolled from current and new TSC patients at each of the 5 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: 3 years - 21 years 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.
  • History of major brain trauma or surgery, including SEGA resection or epilepsy surgery
  • Contraindications to 3T MRI scanning, such as metal implants/non-compatible medical devices or medical conditions, including vagus nerve stimulator.
  • History of systemic (oral or intravenous) treatment with mTOR inhibitors, such as everolimus or sirolimus. Topical treatment with mTOR inhibitors is permitted.

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


Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California at Los Angeles
Los Angeles, California, United States, 90095
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas at Houston
Houston, Texas, United States, 77030
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)
Investigators
Study Chair: Darcy Krueger, MD, PhD Children's Hospital Medical Center, Cincinnati

Responsible Party: Mustafa Sahin, Assistant in NeurologyAssociate Professor of Neurology, Harvard Medical School, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT02461459     History of Changes
Other Study ID Numbers: IRB-P00013585
1U54NS092090 ( U.S. NIH Grant/Contract )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: October 2, 2018
Last Verified: October 2018

Keywords provided by Mustafa Sahin, Boston Children’s Hospital:
Tuberous Sclerosis Complex
TSC
Autism
ASD
Intellectual Disability
ID
MRI

Additional relevant MeSH terms:
Disease
Sclerosis
Autistic Disorder
Autism Spectrum Disorder
Intellectual Disability
Tuberous Sclerosis
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