Quantification of Elastin Markers Synthesis in Williams-Beuren Syndrome and 7q11.23 Micro-duplication Syndrome (ELAST7)

Introduction: Williams-Beuren syndrome is a rare genetic disorder caused by a 7q11.23 microdeletion. The phenotype associates vasculopathy (arterial stenosis, hypertension), dimorphism and intellectual disability. Microdeletion includes several genes: ELN encodes for elastin and the haplo-insufficiency (only 1 functional copy) causes vasculopathy.

The primary objective is to quantify plasma and urinary levels of elastin peptides in Williams-Beuren patients and 7q11.23 micro-duplication syndrome patients in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship "gene copy number - circulating levels of markers) Materials and Methods: This prospective study will be carried out in Lyon at the "Hôpital Femme-Mère-Enfant" for 2 years. 3 groups of patients will be studied: Williams-Beuren patients (N=20), micro-duplication 7q11.23 syndrome patients (N=10) and healthy patients (N=60). Subjects will be followed for 1 day.

Clinical examination (weight, height, blood pressure) and biological sample collection (blood and urine sample) will be carry out for Williams Beuren and micro-duplication 7q11.23 patients group. A large majority of visits will be part of patients' usual care. A large part of patients are systematically seen in consultation once a year. For healthy group, only biological sample collection will be carry out. The PE concentrations will be assessed and compared between the three groups of patients.

Study Overview

• Status: Unknown
• Conditions: Williams-Beuren Syndrome; Micro-duplication 7q11.23 Syndrome; Vasculopathy
• Intervention / Treatment: Biological: Physical examination and Urine and blood samples; Biological: Urine and blood samples

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Massimiliano ROSSI, Dr; Phone Number: +33 04 27 85 55 72; Email: Massimiliano.rossi@chu-lyon.fr
• Study Contact Backup: Name: Linda PONS, Dr; Phone Number: +33 04.27.85.51.43; Email: linda.pons@chu-lyon.fr

Study Locations

• France
  • Bron, France, 69677
    • Hôpital Femme Mère Enfant - Hospices Civils de Lyon
    • Contact: Massimiliano ROSSI, Dr; Phone Number: +33 04 27 85 55 72; Email: Massimiliano.rossi@chu-lyon.fr
    • Contact: Linda PONS, Dr; Phone Number: +33 04.27.85.51.43; Email: linda.pons@chu-lyon.fr
    • Principal Investigator: Massimiliano ROSSI, Dr
    • Sub-Investigator: Patrick EDERY, Pr
    • Sub-Investigator: Damien SANLAVILLE, Pr
    • Sub-Investigator: Aurélia BERTHOLET-THOMAS, Dr
    • Sub-Investigator: Aurélie PORTEFAIX, Dr
    • Sub-Investigator: Lionel BOUVET, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 58 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age : from 3 months to 60 years old
• Williams Beuren group : Diagnosis confirmed with FISH
• Micro-duplication 7q11.23 group : Diagnosis confirmed with CGHarray
• Healthy Group : no cardiovascular and neurological medical history
• Informed consent

Exclusion Criteria:

• No social insurance
• Subject under judicial protection
• Subject participating in another research including an exclusion period still in progress

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Williams Beuren; Subjects aged from 3 months to 60 years with a diagnosis confirmed with FISH of Williams Beuren syndrome.	Biological: Physical examination and Urine and blood samples; Only one visit for each participant : A large majority of visits will be part of patients' usual care; Medical examination : birth, weight, gender, blood pressure, medical history; Urine and blood samples
Other: Micro-duplication 7q11.23; Subjects aged from 3 months to 60 years with a diagnosis confirmed with CGHarray of micro-duplication 7q11.23 syndrome.	Biological: Physical examination and Urine and blood samples; Only one visit for each participant : A large majority of visits will be part of patients' usual care; Medical examination : birth, weight, gender, blood pressure, medical history; Urine and blood samples
Other: Healthy Group; Subjects without cardiovascular and neurological medical history.	Biological: Urine and blood samples; Only one visit for each participant; Medical history; Urine and blood samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma level of elastin peptides (PE)	To quantify plasma level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship "gene copy number - circulating levels of markers). The primary endpoint will be assessed by measuring the blood level of PE between groups	1 day
Urinary level of elastin peptides (PE)	To quantify urinary level of elastin peptides in participants in order to correlate the levels of these markers with the number of copies of ELN gene (proportional positive relationship "gene copy number - circulating levels of markers). The primary endpoint will be assessed by measuring the urinary level of PE between groups	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between blood level of PE and cardiovascular involvement in patients.	Blood level of PE will be correlated with the presence / severity of cardiovascular disease	1 day
Correlation between urinary level of PE and cardiovascular involvement in patients.	Urinary level of PE will be correlated with the presence / severity of cardiovascular disease	1 day
Blood level of PE in treated and untreated minoxidil patients	Blood levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study	1 day
Urinary level of PE in treated and untreated minoxidil patients	Urinary levels of PE in the samples of patients who participated in the minoxidil clinical trial will be compare to those of participants of this study	1 day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): October 1, 2021

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Vasculopathy; Williams-Beuren Syndrome; Micro-duplication 7q11.23 syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Aortic Valve Disease; Heart Valve Diseases; Intellectual Disability; Chromosome Disorders; Aortic Valve Stenosis; Aortic Stenosis, Supravalvular; Syndrome; Vascular Diseases; Williams Syndrome
• Other Study ID Numbers: 69HCL18_0368

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