Physiological Abnormalities Associated with Down Syndrome

NCT03087500 | Withdrawn

• 1 other identifier: 206522
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Down Syndrome

Keywords

Down Syndrome; Typically Developing Participants; Children; Adolescents; Adults

Outcome Measures

Primary Outcomes (9)

• Microbiome Analysis

  Stool will be collected for Microbiome Analysis on cases and controls

  2 years

• Mitochondrial Function Analysis

  The Seahorse XR extracellular flux analyzer will be used to measure mitochondrial function in cases and controls

  2 years

• Oxidative Stress Analysis

  Thiol measurements will be collected and analyzed between cases and controls

  2 years

• Immune Function

  Salivary measurements of cytokines will be collected on cases and controls

  2 years

• Metabolomics

  Urine will be collected for metabolomics analysis on cases and controls

  2 years

• Epigenetics

  Epigenetics will be evaluated on cases and controls

  2 years

• Folate Receptor Alpha Autoantibody (FRAA)

  Serum will be collected for FRAA analysis on cases and controls

  2 years

• 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

• 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

Study Arms (2)

Down Syndrome (DS)

120 clinically confirmed full trisomy 21, age 3-50 years of both sexes will be recruited as the target study population. Half of the individuals (n=60) will be children (3-17 years of age) while half (n=60) will be adults (18-50 years of age)

Other: There is no other intervention, only clinical treatment.

Typically Developing Controls

60 typically developing individuals age 3-50, age and gender matched to at least one participant with DS. Half of the controls (n=30) will be age and gender match to children with DS and half (n=30) will be age and gender matched to adults with DS.

Other: There is no other intervention, only clinical treatment.

Interventions

There is no other intervention, only clinical treatment. OTHER

There is no other intervention, only clinical treatment.

Down Syndrome (DS); Typically Developing Controls

Eligibility Criteria

• Age: 3 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Downs Syndrome: 120 clinically confirmed full trisomy 21, age 3-50 years of both sexes will be recruited as the target study population. Half of the individuals (n=60) will be children (3-17 years of age) while half (n=60) will be adults (18-50 years of age) Control Subjects: 60 typically developing individuals age 3-50, age and gender matched to at least one participant with DS. Half of the controls (n=30) will be age and gender match to children with DS and half (n=30) will be age and gender matched to adults with DS.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Arkansas: lead
• Down Syndrome Research Foundation: collaborator
• Arkansas Children Research Institute: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Biomarkers of oxidative stress (GSH/GSSG) * Biomarkers of reduced methylation capacity (SAM/SAH) * Biomarkers of mitochondrial energetics * Metabolomics (Urine, Blood) * Salivary inflammatory cytokines (IL-1, IL2, IL-6, TNFα) * DNA methylation array (epigenetic profile); total DNA methylation * Folate Receptor Autoantibody (Blocking and Binding) * Thyroid Function (Thyroid Stimulating Hormone, T3, Reverse T3 and free and total T4) * Microbiome Analysis (Stool)

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Richard Frye

  Arkansas Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: March 22, 2017
• Study Start: October 1, 2017
• Primary Completion: October 1, 2017
• Study Completion: December 1, 2019
• Last Updated: September 3, 2024

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share