The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy
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|ClinicalTrials.gov Identifier: NCT03396562|
Recruitment Status : Recruiting
First Posted : January 11, 2018
Last Update Posted : January 11, 2022
|Condition or disease||Intervention/treatment|
|Klinefelter Syndrome Trisomy X XYY Syndrome XXXY and XXXXY Syndrome Xxyy Syndrome Xyyy Syndrome Xxxx Syndrome Xxxxx Syndrome Xxxyy Syndrome Xxyyy Syndrome Xyyyy Syndrome Male With Sex Chromosome Mosaicism||Other: Assessments of Development and Growth|
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|
|Estimated Enrollment :||300 participants|
|Official Title:||The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy|
|Actual Study Start Date :||September 29, 2017|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||September 2022|
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.
- 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)
- 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)
- 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)
- Body Mass Index (BMI) [ Time Frame: 36 months ]BMI will be determined through measurement of length and weight at the research visit.
- Z Score [ Time Frame: 36 months ]The z score will be calculated for age group at the research visit.
- 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.
Biospecimen Retention: Samples With DNA
A venous blood, urine and stool samples will be collected at each research visit, with the exception of the 18 and 48 month visit.
Hormone levels (Follicle Stimulating Hormone, Luteinizing Hormone, Anti-Mullerian Hormone, Inhibin B, Estradiol and Testosterone) will be analyzed. Some of the venous blood will be collected for the purpose of banking serum, plasma, RNA and DNA for future studies. Urine and stool samples will also be banked for future analysis.
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): NCT03396562
|Contact: Nicole Tartaglia, MD, MS||(720) firstname.lastname@example.org|
|Contact: Susan Howell, MS, CGC, MBAemail@example.com|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Susan Howell, MS, CGC, MBA 720-777-8361 firstname.lastname@example.org|
|Contact: Mariah Brown (720)777-6774 email@example.com|
|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|
|United States, Pennsylvania|
|Nemours at Thomas Jefferson University||Recruiting|
|Philadelphia, Pennsylvania, United States, 19107|
|Contact: Judith Ross, MD 215-955-1648 firstname.lastname@example.org|
|Contact: Karen Kowal, PAC 215-9559008 email@example.com|
|Principal Investigator: Judith Ross, MD|
|Sub-Investigator: Karen Kowal, PAC|
|Sub-Investigator: Mary Iampietro, PhD|
|Sub-Investigator: Amanda Alston|
|Principal Investigator:||Nicole Tartaglia, MD MS||University of Colorado, Denver|