Physiological Abnormalities Associated With Down Syndrome

Down Syndrome Clinical Trial

Official title:

Physiologic Biomarkers Within the Functional Spectrum of Down Syndrome

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03087500
• Other study ID #: 206522
• Status: Withdrawn
• Start date: October 2017
• Est. completion date: December 2019

Study information

• Verified date: October 2017
• Source: University of Arkansas
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2019
• Est. primary completion date: September 2019
• Gender: All
• Age group: 3 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Down Syndrome
• Syndrome

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University of Arkansas	Arkansas Children Research Institute, Down Syndrome Research Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiome Analysis	Stool will be collected for Microbiome Analysis on cases and controls	2 years
Primary	Mitochondrial Function Analysis	The Seahorse XR extracellular flux analyzer will be used to measure mitochondrial function in cases and controls	2 years
Primary	Oxidative Stress Analysis	Thiol measurements will be collected and analyzed between cases and controls	2 years
Primary	Immune Function	Salivary measurements of cytokines will be collected on cases and controls	2 years
Primary	Metabolomics	Urine will be collected for metabolomics analysis on cases and controls	2 years
Primary	Epigenetics	Epigenetics will be evaluated on cases and controls	2 years
Primary	Folate Receptor Alpha Autoantibody (FRAA)	Serum will be collected for FRAA analysis on cases and controls	2 years
Primary	Thyroid Function	Thyroid measures of Thyroid Stimulating Hormone (TSH), T3, Reverse T3 and free and total T4 will be evaluated on cases and controls	2 years
Primary	Diet	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	2 years