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Tuberous Sclerosis ComplexNCT01780441

Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC)

An observational study of Tuberous Sclerosis Complex, run by Boston Children's Hospital at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The investigators are enrolling 3-12 month old infants with a diagnosis of tuberous sclerosis complex (TSC) for a new study on early markers of autism. The study is looking for early signs for autism in a population (TSC) where autism is common. Read more about this study

Who is it for?
Ages 3 to 12 months
Conditions the study is for
Tuberous Sclerosis Complex
How many people
166 participants
Where
5 sitesUnited States
Study dates
Jan 2013to Dec 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 12 months
  • All sexes
  • No healthy volunteers
  • Child

Study population: A total of 150 evaluable infants with TSC will be recruited. Diagnosis of TSC will be based on established clinical criteria and will not require genetic testing prior to participation. The target age of entry into study is 3-6 months, but infants up to age 12 months (less than or equal to 13.5 months) will be included.

Who may be able to join

  • Meets genetic or clinical diagnostic criteria for TSC (Tuberous Sclerosis), the latter based on current recommendations for diagnostic evaluation, such as physical exam, neuroimaging, echocardiogram.
  • Age criteria: 3 months- 12 months of age at time of enrollment. For study purposes, 3 months is defined as ≥ 9 weeks, 1 day and 12 months is defined as ≤ 13.5 months.

Who cannot join

  • Prematurity, defined as gestational age < 36 weeks at time of delivery
  • Has taken an investigational drug as part of another research study, within 30 days prior to study enrollment
  • Is taking an mTOR inhibitor such as rapamycin, sirolimus, or everolimus (other than topical formulations) at the time of study enrollment
  • Subependymal Giant Cell Astrocytoma requiring medical or surgical treatment at the time of study enrollment
  • History of epilepsy surgery at the time of study enrollment
  • Contraindications to MRI scanning, such as metal implants/non-compatible medical devices or medical conditions

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • University of Texas at Houston

    Houston, Texas, 77030

  • University of California at Los Angeles

    Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Longitudinal Study to Identify Early Biomarkers of Autism Spectrum Disorder (ASD) in Infants With Tuberous Sclerosis Complex (TSC)

The investigators are enrolling 3-12 month old infants with a diagnosis of tuberous sclerosis complex (TSC) for a new study on early markers of autism. The study is looking for early signs for autism in a population (TSC) where autism is common. The goal of this project is to use behavioral testing, MRI and EEG techniques to identify children at risk for developing autism starting at 3 months of age and continuing until 36 months of age. Throughout the study, the investigators will recommend Early Intervention services for any child who shows early signs of autism.

Read the detailed description

This is a five-year multi-site study using MRI and EEG technologies to identify developmental precursors of Autism Spectrum Disorder in patients with Tuberous Sclerosis Complex (TSC). The study will be enrolling infants at five TSC centers throughout the country, including Boston Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Alabama at Birmingham, University of Texas at Houston and University of California Los Angeles. The main goal of this study is to identify early signs of autism in children with TSC looking at the brain through MRI/diffusion tensor imaging, EEG and behavioral/neuropsychological methods. Eligible infants between the ages of 3-12 months will be evaluated longitudinally at regular visit intervals up to 3 years of age.

Study Objectives

  1. To characterize the developmental precursors of ASD in a large number of TSC infants using a prospective multi-center design: Infants with TSC will be evaluated longitudinally at ages 3, 6, 9, 12, 18, 24 and 36 months. At each age, children will undergo standardized evaluations, using cognitive and adaptive measures. At age 24 and 36 months, formal assessment for autism will be performed. Clinical data including medication use, seizure history, EEG activity, genotypic variation, and co-morbidities will be recorded to determine if specific clinical factors modify the course of development.
  2. To identify biomarkers with advanced diffusion tensor imaging (DTI) that help predict development of ASD in TSC infants: The investigators hypothesize that decreased white matter integrity performed annually for each of the first 3 years of life, including DTI sequences with tractography. Radial, axial, and mean diffusivity and fractional anisometry will be calculated for each time point and change over time correlated with development of ASD to determine relative risk. Individual measures at each time point will be compared between ASD and non-spectrum groups to assess the individual impact of each measure and timing.
  3. To identify biomarkers with quantitative EEG that help predict development of ASD in TSC infants: The investigators hypothesize that altered functional connectivity, as measured by qEEG coherence and high frequency oscillations, will correlate with development of ASD in TSC. Quantitative EEG (qEEG), EEG coherence/gamma frequency (30-50Hz), and high frequency oscillations encompassing both ripples (80-250H) and fast ripples (250-500 Hz) will be measured at each time point. Changes over time will be correlated with development of ASD to determine relative risk, as will comparison of individual measures between the two groups. EEG findings will also be correlated with MR results obtained to further couple functional connectivity as measured by EEG with structural connectivity measured by DTI.
Keywords
Tuberous Sclerosis Complex, TSC, Autism, ASD, Biomarkers, Infants
Medical subject headings
Tuberous Sclerosis, Autistic Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01780441
Study groupRoleWhat they receive
Tuberous Sclerosis Complex (TSC)Tuberous Sclerosis Complex

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ADOS evaluation score at the 36 month visit

    The ADOS performed at 24 and 36 months will be used as a preliminary diagnosis for data analysis. The primary outcome is the possible clinical diagnosis of autism spectrum disorder per the DSM 5 guidelines (Autistic Disorder, Asperger's and PDD-NOS).

    Measured: 36 months

  2. MRI biomarkers

    MRI biomarkers obtained at baseline, 12, 24, 36 months will be applied to characterize individual patients in terms of brain tissue, white matter structure and connectivity, functional networks, and pathology. Brain tissue segmentation will be based on structural images derived from T1- and T2-weighted and FLAIR sequences using automated software tools designed for these tasks. White matter integrity and organization will be inferred from DTI imaging sequences. Structural connectivity networks will be delineated by DTI tractography assessment.

    Measured: 36 months

  3. EEG biomarkers

    One-hour video-EEG containing both wakefulness and sleep (minimum of 20 minutes of each) will be obtained at baseline, 3, 6, 9, 12, 18, 24 and 36 months. Functional connectivity and pathological activity will be determined by measurement of EEG coherence and gamma frequency/high frequency oscillations.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionDec 2019
  4. Study completionDec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
166 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01780441
Sponsor's protocol ID
IRB-P00005074
Other IDs
1U01NS082320-01
Status last verified
Feb 2021
First submitted
28 Jan 2013
Last updated
4 Feb 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Sadeghzadeh S, Johnstone TM, Peters JM, Porter BE, Ihnen SKZ. Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex. J Neurosurg Pediatr. 2024 Jul 12;34(4):384-392. doi: 10.3171/2024.4.PEDS2481. Print 2024 Oct 1.

    PubMed 38996393

  • Srivastava S, Prohl AK, Scherrer B, Kapur K, Krueger DA, Warfield SK, Sahin M; TACERN Study Group. Cerebellar volume as an imaging marker of development in infants with tuberous sclerosis complex. Neurology. 2018 Apr 24;90(17):e1493-e1500. doi: 10.1212/WNL.0000000000005352. Epub 2018 Mar 23.

    PubMed 29572283

Questions about this trial

What is this clinical trial studying?

An observational study of Tuberous Sclerosis Complex, run by Boston Children's Hospital at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ADOS evaluation score at the 36 month visit (time frame: 36 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01780441, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.

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