Correlation Between Optic Nerve Vessel Anomalies, Serum Angiogenic Factors and Renal Anomalies in Down Syndrome Children (DOPANUR)

Interventional Controlled Cross-sectional Study Assessing the Correlation Between Optic Nerve Vessels Anomalies, Serum Angiogenic Factors and Renal Anomalies in Children With Down Syndrome.

In approximately half of individuals with Down syndrome, an higher than normal number of vessels cross the optic disc margin. Investigator hypothesize that early retinal vessel branching occurs due to inhibition of angiogenesis by triplet overexpression of endostatin, an angiogenesis inhibitor encoded on chromosome 21. Since angiogenesis is critical in the development of eyes and other organs angiogenesis depended (specially kidney, brain, and recently described lungs and heart), early branching of retinal vessels at the level of the optic disc would also likely result in abnormal renal and other organs development in these individuals. Investigator wish to determine whether observation of optic disc vessels may serve as an indicator of elevated endostatin levels and other angiogenesis-dependent organs anomalies.

Study Overview

• Status: Unknown
• Conditions: Down Syndrome
• Intervention / Treatment: Diagnostic test: Funduscopic examination and retinal photography; Diagnostic test: Serum levels of endostatin and angiogenesis factors; Diagnostic test: Renal and low urinary tract Doppler ultrasound; Diagnostic test: Urinalysis; Diagnostic test: Anthropometric measures and vitals signs

Detailed Description

Investigator will measure the serum levels of endostatin as well as others angiogenetic factors in Down syndrome children versus control group 1 constituted by the patient mothers.

Investigator will also perform renal and low urinary tract Doppler ultrasound with measurement of renal dimension in order to determine if the kidneys of patients with high level of serum of endostatin are smaller than those of patients with normal level of endostatin. Data observed in Down syndrome children will be compared to control group 2age constituted by sex and age matched healthy children Urine microalbuminuria and urine microalbuminuria/creatinuria from the first urine in the morning will be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lavina Postolache, MD; Phone Number: 0032 2 477 21 92; Email: lavina.postolache@huderf.be

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Recruiting
    • Hôpital Universitaire des Enfants Reine Fabiola
    • Contact: Lavina Postolache, MD; Phone Number: 0032 2 477 21 92; Email: lavina.postolache@huderf.be
    • Principal Investigator: Lavina Postolache, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of personally signed and dated informed consent document by adult subject or parents
• When capable of providing assent, provision of personally signed and dated informed assent document by children
• Subjects and/or their caregivers/parents are willing and able to comply with scheduled laboratory tests, and other required study procedures.

Exclusion Criteria:

• Inability to cooperate with study related examination

For "Study Group" subjects

• Known chronic diseases unrelated to their triallelic condition For "Control Group n°1" & "Control Group n°3"
• General disease in which the level of endostatin may be modified such as leukemia, cancers, inflammatory diseases (e.g.: rheumatoid arthritis, Crohn's disease, psoriasis)
• Any condition that may cause a hypoxia
• Pregnancy

For "Control Group n°2":

• Healthy children except benign ophthalmological refraction anomalies
• Any known renal or low urinary tract diseases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Study group; Down Syndrome children	Diagnostic test: Funduscopic examination and retinal photography; A standardized funduscopic examination and retinal photography will be performed by an ophthalmologist focusing on optic nerve.; Diagnostic test: Serum levels of endostatin and angiogenesis factors; Serum levels of endostatin, angiopoietin and vaso endothelial growth factor will be analyzed; Diagnostic test: Renal and low urinary tract Doppler ultrasound; Measurements of each kidney will include maximum renal bipolar length in a sagittal plane, renal width and thickness in an axial plane perpendicular to each other at the level of renal hilum and cortical thickness. Intensity of corticomedullary differentiation will estimated. Doppler ultrasound examination will assess renal arterial resistivity indexes; Diagnostic test: Urinalysis; Urinalysis assessments will include assessments of microalbuminuria and microalbuminuria to creatinuria ratio. A spot urine sample will be collected from first morning void.; Diagnostic test: Anthropometric measures and vitals signs; weight, height and blood pressure will be assessed
Other: Control group n°1; Down Syndrome children's mothers	Diagnostic test: Funduscopic examination and retinal photography; A standardized funduscopic examination and retinal photography will be performed by an ophthalmologist focusing on optic nerve.; Diagnostic test: Serum levels of endostatin and angiogenesis factors; Serum levels of endostatin, angiopoietin and vaso endothelial growth factor will be analyzed
Other: Control group n°2; Age and sex matched healthy children	Diagnostic test: Funduscopic examination and retinal photography; A standardized funduscopic examination and retinal photography will be performed by an ophthalmologist focusing on optic nerve.; Diagnostic test: Renal and low urinary tract Doppler ultrasound; Measurements of each kidney will include maximum renal bipolar length in a sagittal plane, renal width and thickness in an axial plane perpendicular to each other at the level of renal hilum and cortical thickness. Intensity of corticomedullary differentiation will estimated. Doppler ultrasound examination will assess renal arterial resistivity indexes; Diagnostic test: Urinalysis; Urinalysis assessments will include assessments of microalbuminuria and microalbuminuria to creatinuria ratio. A spot urine sample will be collected from first morning void.; Diagnostic test: Anthropometric measures and vitals signs; weight, height and blood pressure will be assessed
Other: Control group n°3; Down syndrome children's healthy siblings	Diagnostic test: Funduscopic examination and retinal photography; A standardized funduscopic examination and retinal photography will be performed by an ophthalmologist focusing on optic nerve.; Diagnostic test: Serum levels of endostatin and angiogenesis factors; Serum levels of endostatin, angiopoietin and vaso endothelial growth factor will be analyzed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the number of retinal vessels crossing the optic disc and serum level of endostatin	correlation coefficent	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between the number of retinal vessels crossing the optic disc and serum level of other angiogenic factors	correlation coefficent	18 months
Correlation between serum level of endostatin and serum level of other angiogenic factors	correlation coefficient	18 months
Description of renal anomalies in Down syndrome.	absolute number and type of renal anomalies	18 months
Comparison of prevalence of renal anomalies between Down syndrome and healthy subjects	Proportion and type of disease	18 months
Correlation between the number of optic nerve vessels and the presence of organs pathologies	correlation coefficient	18 months
Correlation between serum level of angiogenesis factors and the presence of organs pathologies	correlation coefficient	18 months

Collaborators and Investigators

• Sponsor: Queen Fabiola Children's University Hospital
• Investigators: Principal Investigator: Lavina Postolache, MD, Queen Fabiola Children's University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2017
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: June 27, 2017
• First Submitted That Met QC Criteria: June 30, 2017
• First Posted (Actual): July 2, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 3, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Congenital Abnormalities; Down Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Endostatins; Angiogenesis Inducing Agents
• Other Study ID Numbers: P2017/Ophtalmo/DOPANUR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No