Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia

NCT03234127 | Completed

• 1 other identifier: RC17_0244
• Study Type: interventional
• Target: 562
• Locations: 1 country
• Sites: 9

Brief Summary

The main objective of SAFIR is to identify the atherosclerotic genetic factors in these patients, which will identify new therapeutic targets for the treatment of CV and Familial Hypercholesterolemia diseases. In addition, SAFIR will allow the identification of new CV protection biomarkers, which will be useful tools for the development of a personalized medicine for the management of dyslipidemias.

Conditions

Homozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia

  Identification of functional genetic variants by a Whole Genome Sequencing (WGS) approach in case-control analysis (FH without and with advanced coronary atherosclerosis) and/or family analysis (protected and affected relatives)

  3 years

Secondary Outcomes (6)

• Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.

  3 years

• Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients

  3 years

• Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients

  3 years

• Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients

  3 years

• Association between aortic valvular score and development of coronary atherosclerosis in FH patients

  3 years

Study Arms (3)

Atherosclerosis- resistance

OTHER

FH Patient without atherosclerosis

Genetic: Whole Genome Sequencing

Control

OTHER

FH patient with atheroclerosis

Genetic: Whole Genome Sequencing

the related population without familial hypercholesterolemia

OTHER

No FH patient

Genetic: Whole Genome Sequencing

Interventions

Whole Genome Sequencing GENETIC

Whole Genome Sequencing Biomarkers analyses

Also known as: Biological analyzes

Atherosclerosis- resistance; Control; the related population without familial hypercholesterolemia

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient agreeing to sign the consent of the study and the consent of biocollection
• Patient suffering from a familial hypercholesterolemia with a clinically-biologic score DLCN (Dutch Lipid Clinic Network, Annex 2)\> 8 and / or a causative mutation identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.
• Men ≥ 40 years of age; Female ≥ 50 years
• Patient affiliated to an existing social insurance
• Subject in secondary prevention of an atheromatous disease: coronary event or ischemic heart disease, irrespective of the result of the coronary calcium score; Ischemic stroke with proven carotid atheromatosis; revascularization (angioplasty, bypass surgery) or amputation in PAD
• Primary prevention topic CV with calcium score ≥ 400 Agatston units
• \- No cardiovascular event (including MI, coronary revascularization, angina, stroke \&, Transiant ischemic attack of atheromatous origin, PAD) with: For women between 50 and 65 years, a nil calcium score \* For women between 65 and 75 years of age, a calcium score\*\* ≤ 10 Agatston units For women over 75 years of age, a calcium score\*\* ≤ 20 Agatston units For men between 40 and 55 years of age, a nil calcium score\* for men For men between 55 and 70 years of age, a calcium score\*\* ≤ 10 Agatston units For men over 70 years of age, a calcium score\*\* ≤ 20 Agatston units
• year old men and 50 year old women: less than 6 months old
• year old men and 51 year old women: under 1 year old
• year old men and 52 year old women: under 2 years old
• year old men and 53 year old women: under 3 years old
• year old men and 54 year old women: under 4 years old
• Less than 5 years
• Patient agreeing to sign the consent of the study and the consent of biocollection
• Patient suffering from a familial hypercholesterolemia with a clinically-biologic score DLCN (Dutch Lipid Clinic Network, Annex 2)\> 8 and / or a causative mutation identified in the LDL receptor genes, apolipoprotein B100 or Of PCSK9.

You may not qualify if:

• Subject suffering from active cancer or progressive neoplasia
• Subject treated with recent corticosteroid therapy
• Subjects with unsubstituted or poorly controlled hypothyroidism (TSH\> normal)
• Subject receiving immunosuppressive or anti-cancer treatment
• Subject refusing to participate
• Subjects under tutelage, curatorship or a safeguard of justice or without social insurance
• \- Subject with no "definite" familial hypercholesterolemia according to the DLCN score (≤8), after auction. The purpose of the auction will be to rule on the causal nature of an identified mutation.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (9)

Le Bocage Hospital

Dijon, 29079, France

Location

CHRU de Lille

Lille, 59037, France

Location

Louis Pradel Cardiovascular Hospital

Lyon, 69677, France

Location

La Conception Hospital

Marseille, 13285, France

Location

Nantes University Hospital

Nantes, 44093, France

Location

Saint-Antoine Hospital

Paris, 75012, France

Location

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

Rennes University Hospital

Rennes, 35033, France

Location

Toulouse Hospital

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Hyperlipoproteinemia Type II; Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: December 6, 2017
• Primary Completion: May 6, 2021
• Study Completion: May 6, 2021
• Last Updated: May 24, 2021

Record last verified: 2021-05

Locations

FR (9)