The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy

January 6, 2022 updated by: University of Colorado, Denver
This study is designed to research the natural history of neurodevelopment, health and early hormonal function in infants with XXY/Klinefelter syndrome, XYY, XXX and other sex chromosome variations in an effort to identify early predictors of developmental and health outcomes. The Investigators will also evaluate different developmental screening tools in infants with sex chromosome variations so the investigators can develop recommendations for pediatrician caring for infants and young children with XXY/Klinefelter syndrome, XYY, XXX, and other sex chromosome variations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background: Sex Chromosome Trisomies (SCT) including Klinefelter (XXY), Trisomy X (XXX), and XYY syndromes occur in 1 out of every 500 births and are associated with a broad phenotypic spectrum including increased risk for developmental delays (DD), language/learning disorders, and autism spectrum disorder (ASD). XXY is also associated with testicular failure, XXX increases risk for ovarian failure, and disorders of insulin resistance and other medical problems resulting in increased morbidity and mortality occur in all 3 SCTs. Historically, less than 10% of SCT diagnoses occur in childhood, however the rate of newborns with SCT has markedly increased with new noninvasive prenatal cell-free DNA (cfDNA) screening. SCT natural history research is limited to studies from the 1970's, and the investigators have little knowledge of early predictors of the wide heterogeneity in later outcomes. The high risk for DD in SCT suggests that newborn screening may improve identification for DD and timely initiation of interventions. However, it is not clear whether all SCT infants indeed require intensive developmental assessments and therapies, or if primary care screenings are sufficient to identify those in need. The surge in prenatal SCT diagnoses from cfDNA methods provides an opportunity for longitudinal study of a cohort of infants to explore natural history, and to improve care.

Aims: This study aims to: (1) describe and compare the natural history of neurodevelopment, health and early gonadal function in infants with the 3 SCT conditions through a national prospective eXtraordinarY Babies Study in partnership with the Newborn Screening Translational Research Network (NBSTRN), (2) identify early predictors of poor neurodevelopmental and cardiometabolic outcomes, and (3) evaluate the sensitivities of common primary care developmental screening measures to detect DD and ASD in this high-risk population to inform recommendations for an early neurodevelopmental care protocol.

Approach: Infants with a prenatal diagnosis of XXY, XYY, or XXX will be followed prospectively every 6-12 months for 2-4 years at 2 eXtraordinarY Kids Clinic sites. Demographics, health history, development, interventions, and social/family history will be collected. Assessments will include: (1) measures of cognitive, language, social, motor, and adaptive function, (2) physical exam, gonadal function labs, cardiometabolic measures, and body composition, and (3) quality of life outcomes. Impact: Prospective study of the natural history of prenatally diagnosed infants with SCT will allow investigation of important questions to inform newborn screening considerations, such as the interplay between early hormonal profiles and developmental outcomes. Results will be immediately relevant for counseling and establishing evidence-based care guidelines for the rapidly increasing rate of SCT diagnoses from cfDNA screening. Results will serve as the basis for ongoing longitudinal studies of health and psychological outcomes of SCTs through the lifespan.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
        • Contact:
        • Contact:
        • Principal Investigator:
          • Nicole Tartaglia, MD MS
        • Sub-Investigator:
          • Shanlee Davis, MD MSCS
        • Sub-Investigator:
          • Mariah Brown
        • Sub-Investigator:
          • Tanea Tanda
        • Sub-Investigator:
          • Susan Howell, MS
        • Sub-Investigator:
          • Lisa Cordeiro, MS, CSP
        • Sub-Investigator:
          • Rebecca Wilson, PsyD
        • Sub-Investigator:
          • Jennifer Janusz, PsyD
        • Sub-Investigator:
          • Laura Pyle, PhD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Nemours at Thomas Jefferson University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Judith Ross, MD
        • Sub-Investigator:
          • Karen Kowal, PAC
        • Sub-Investigator:
          • Mary Iampietro, PhD
        • Sub-Investigator:
          • Amanda Alston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Sex Chromosome Trisomies (SCT) including Klinefelter (XXY), Trisomy X (XXX), and XYY. Rare sex tetrasomy and pentasomy conditions are also eligible.

Description

Inclusion Criteria:

  1. Prenatal diagnosis of sex chromosome aneuploidy (by cfDNA, chorionic villi sampling, and/or amniocentesis)
  2. Postnatal confirmatory karyotype of XXY, XYY, XXX, XXYY, XYYY, XXXY, XXXX, XXXXX, XXXXY, XXXYY, XXYYY, XYYYY (including any mosaicism with <80% 46,XX or 46,XY cell line)
  3. English or Spanish speaking
  4. Age 6 weeks to 12 months 30 days on enrollment

Exclusion Criteria:

  1. Previous diagnosis of a different genetic or metabolic disorder with neurodevelopmental or endocrine involvement
  2. Prematurity less than 34 weeks gestational age
  3. Complex congenital malformation not previously associated with sex chromosome aneuploidy
  4. History of significant neonatal complications (ie intraventricular hemorrhage, meningitis, hypoxic-ischemic encephalopathy)
  5. Known complex Central Nervous System (CNS) malformation identified by neuroimaging

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
SCT Conditions

Sex Chromosome Trisomies Conditions including Klinefelter (XXY), Trisomy X (XXX), XXY Syndromes.

Interventions: Longitudinal observational assessments of development and growth at ages: 2 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, and 5 or 6 years.
Other: Assessments of Development and Growth
Longitudinal observational assessments of development and growth at ages: 2 months, 6 months, 12 months, 18 months, 24 months, 36 months, 48 months, and 5 or 6 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal Descriptive Statistics of Cognitive Scores on the Bayley-III
Time Frame: 36 months
Cognitive skills will be assessed using the standardized Bayley Scales of Infant Development--3rd Edition (Bayley-3)
36 months
Longitudinal Descriptive Statistics of Motor Scores on the Bayley-III
Time Frame: 36 months
Motor development will be assessed using the standardized Bayley Scales of Infant Development--3rd Edition (Bayley-3)
36 months
Longitudinal Descriptive Statistics of Language Scores on Bayley-III
Time Frame: 36 months
Language development will be assessed using the Bayley Scales of Infant Development--3rd Edition (Bayley-3)
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Mass Index (BMI)
Time Frame: 36 months
BMI will be determined through measurement of length and weight at the research visit.
36 months
Z Score
Time Frame: 36 months
The z score will be calculated for age group at the research visit.
36 months
Body Composition (% body fat)
Time Frame: 3 year old visit
Body fat percentage will be measured using air Dual Energy X-Ray Absorptiometry (DEXA) at 3 year old visit.
3 year old visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Investigators

  • Principal Investigator: Nicole Tartaglia, MD MS, University of Colorado, Denver

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 29, 2017

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

September 1, 2022

Study Registration Dates

First Submitted

December 5, 2017

First Submitted That Met QC Criteria

January 9, 2018

First Posted (Actual)

January 11, 2018

Study Record Updates

Last Update Posted (Actual)

January 11, 2022

Last Update Submitted That Met QC Criteria

January 6, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-0118

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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