Physiological Abnormalities Associated With Down Syndrome

Withdrawn

• Conditions: Down Syndrome

• Registration Number: NCT03087500
• Lead Sponsor: University of Arkansas

Brief Summary

The overall goal of this study is to evaluate biomarkers of oxidative stress, mitochondrial function, and DNA methylation (epigenetics) in order to determine the extent to which these biomarkers are related to cognitive, behavioral and adaptive function in Down Syndrome. The inter-relationship between measurable biomarkers and functional/cognitive abilities will move beyond genetics to provide unprecedented new knowledge and a broader understanding of the underlying pathophysiology and abnormal gene expression induced by trisomy 21.

Detailed Description

The Investigators preliminary evidence indicates that people with DS have metabolic biomarkers associated with oxidative stress (GSH/GSSG) and reduced methylation capacity (SAM/SAH) as well as abnormal DNA methylation (epigenetics). The investigative team hypothesize that these abnormal metabolic processes contribute to abnormalities in behavior and development associated with trisomy 21; this connection has never been investigated. Confirming and expanding on the preliminary data would provide new understanding of the biological and functional etiology of the behavioral and developmental delays associated with Trisomy 21. Further, establishing the underlying relationship between metabolic abnormalities and behavioral/cognitive function over the age spectrum can provide strong support for the design of future treatments of individuals with DS aimed at improving their behavior and development. In addition, these biomarkers may also prove to be predictive biomarkers for the risk of developing ASD like behaviors or Alzheimer's disease in this population. Finally, examining the modulating role of diet in the severity of biological abnormalities will provide new information for lifestyle guidance to improve biomarkers and potentially minimize the medical co-morbidities associated with trisomy 21.

Study Timeline

• Study First Submitted: 2017-03-09
• Study First Submitted QC: 2017-03-16
• Study First Posted: 2017-03-22
• Status Verified: 2017-10
• Study Start: 2017-10
• Primary Completion: 2019-09
• Study Completion: 2019-12
• Last Update Submitted: 2021-08-02
• Last Update Posted: 2021-08-03

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Participant or guardian ability to consent/assent and willing to comply with protocol requirements

Exclusion Criteria

1. Trisomy translocation or mosaics.
2. Untreated hypothyroidism
3. Known history of liver disease, renal disease, Hepatitis B or C or HIV
4. Recent infection with fever or requiring hospitalization within past 30 days.
5. Any medical condition, use of medications, nutrient or herbal supplements that would interfere with the study results as determined by the PI
6. Chemotherapy
7. Recent surgery (within 2 months)
8. Untreated Epilepsy
9. Any chronic medical/behavioral condition and/or treatments that may interfere with study related outcomes, as determined by PI
10. Dementia
11. History of a significant adverse reaction to a prior blood draw
12. Any other historical event/information that may, in the opinion of the PI, be a reason to exclude the child from participation.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Folate Receptor Alpha Autoantibody (FRAA)	2 years	Serum will be collected for FRAA analysis on cases and controls
Thyroid Function	2 years	Thyroid measures of Thyroid Stimulating Hormone (TSH), T3, Reverse T3 and free and total T4 will be evaluated on cases and controls
Diet	2 years	Examine the modulating role of diet in the severity of biological abnormalities will provide new information for lifestyle guidance to improve biomarkers and potentially minimize the medical co-morbidities associated with trisomy 21. Dietary contributions will be evaluated on cases and controls
Mitochondrial Function Analysis	2 years	The Seahorse XR extracellular flux analyzer will be used to measure mitochondrial function in cases and controls
Metabolomics	2 years	Urine will be collected for metabolomics analysis on cases and controls
Microbiome Analysis	2 years	Stool will be collected for Microbiome Analysis on cases and controls
Immune Function	2 years	Salivary measurements of cytokines will be collected on cases and controls
Epigenetics	2 years	Epigenetics will be evaluated on cases and controls
Oxidative Stress Analysis	2 years	Thiol measurements will be collected and analyzed between cases and controls