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Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia (SAFIR)

Primary Purpose

Homozygous Familial Hypercholesterolemia

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Whole Genome Sequencing
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Homozygous Familial Hypercholesterolemia

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

The inclusion criteria to be met in the population with known coronary atheroma:

  • 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

Inclusion criteria to be met in the population without cardiovascular risk:

- 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

  • 40 year old men and 50 year old women: less than 6 months old
  • 41 year old men and 51 year old women: under 1 year old
  • 42 year old men and 52 year old women: under 2 years old
  • 43 year old men and 53 year old women: under 3 years old
  • 44 year old men and 54 year old women: under 4 years old

    • Less than 5 years

Inclusion criteria to be met in the related population with familial hypercholesterolemia :

  • 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 or Female ≥ 30 years
  • Patient affiliated to an existing social insurance

Inclusion criteria to be met in the related population without familial hypercholesterolemia :

  • Patient agreeing to sign the consent of the study and the consent of biocollection
  • Patient not suffering from a familial hypercholesterolemia related to one of the members of the population suffering from familial hypercholesterolemia without cardiovascular risk
  • Men or Female ≥ 18 years
  • Patient affiliated to an existing social insurance

Exclusion Criteria:

  • 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

The exclusion criterion for all populations except the related population without familial hypercholesterolemia:

- 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.

Sites / Locations

  • Le Bocage Hospital
  • CHRU de Lille
  • Louis Pradel Cardiovascular Hospital
  • La Conception Hospital
  • Nantes University Hospital
  • Saint-Antoine Hospital
  • Pitié-Salpêtrière Hospital
  • Rennes University Hospital
  • Toulouse Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

Other

Arm Label

Atherosclerosis- resistance

Control

the related population without familial hypercholesterolemia

Arm Description

FH Patient without atherosclerosis

FH patient with atheroclerosis

No FH patient

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.
Lipidic panel, phosphocalcic panel, Ceramides, Alipoproteins, Lp(a), lipidomic, LDL size, Phospholipids, TMAO, Carnitin, Cholin, microbiota, metabolomic, LDL Ox, Sterols, Isoprostan, oxidation, inflammation, cytokins, oxidative stress.
Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients
Measurement of arterial stiffness measured by popmeter® (pulse wave velocity)
Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients
Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque)
Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients
Measurement of lower extremity involvement by arterial doppler ultrasonography
Association between aortic valvular score and development of coronary atherosclerosis in FH patients
Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan
Association between coronary calcium score and aortic valvular score in HF patients
Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan

Full Information

First Posted
July 26, 2017
Last Updated
May 21, 2021
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03234127
Brief Title
Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Acronym
SAFIR
Official Title
Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
December 6, 2017 (Actual)
Primary Completion Date
May 6, 2021 (Actual)
Study Completion Date
May 6, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The objective of the SAFIR study is to perform non-invasive coronary vascular phenotyping of familial hypercholesterolemia (FH) families by performing a coronary calcium score and then to detect protective genetic factors in patients who do not have a significant atheroma despite a perturbed biological phenotype. The investigators will also conduct biochemical, lipidemic and metabolomic analyzes to identify a signature of biomarkers protective of cardiovascular risk in FH patients. The investigators will use the French FH register, which already includes 3889 patients, to identify these "protected" FH families within the main reference centers for the management of FH for inclusion and follow-up of patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Homozygous Familial Hypercholesterolemia

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
562 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atherosclerosis- resistance
Arm Type
Other
Arm Description
FH Patient without atherosclerosis
Arm Title
Control
Arm Type
Other
Arm Description
FH patient with atheroclerosis
Arm Title
the related population without familial hypercholesterolemia
Arm Type
Other
Arm Description
No FH patient
Intervention Type
Genetic
Intervention Name(s)
Whole Genome Sequencing
Other Intervention Name(s)
Biological analyzes
Intervention Description
Whole Genome Sequencing Biomarkers analyses
Primary Outcome Measure Information:
Title
Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia
Description
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)
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.
Description
Lipidic panel, phosphocalcic panel, Ceramides, Alipoproteins, Lp(a), lipidomic, LDL size, Phospholipids, TMAO, Carnitin, Cholin, microbiota, metabolomic, LDL Ox, Sterols, Isoprostan, oxidation, inflammation, cytokins, oxidative stress.
Time Frame
3 years
Title
Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients
Description
Measurement of arterial stiffness measured by popmeter® (pulse wave velocity)
Time Frame
3 years
Title
Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients
Description
Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque)
Time Frame
3 years
Title
Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients
Description
Measurement of lower extremity involvement by arterial doppler ultrasonography
Time Frame
3 years
Title
Association between aortic valvular score and development of coronary atherosclerosis in FH patients
Description
Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan
Time Frame
3 years
Title
Association between coronary calcium score and aortic valvular score in HF patients
Description
Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 The inclusion criteria to be met in the population with known coronary atheroma: 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 Inclusion criteria to be met in the population without cardiovascular risk: - 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 40 year old men and 50 year old women: less than 6 months old 41 year old men and 51 year old women: under 1 year old 42 year old men and 52 year old women: under 2 years old 43 year old men and 53 year old women: under 3 years old 44 year old men and 54 year old women: under 4 years old Less than 5 years Inclusion criteria to be met in the related population with familial hypercholesterolemia : 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 or Female ≥ 30 years Patient affiliated to an existing social insurance Inclusion criteria to be met in the related population without familial hypercholesterolemia : Patient agreeing to sign the consent of the study and the consent of biocollection Patient not suffering from a familial hypercholesterolemia related to one of the members of the population suffering from familial hypercholesterolemia without cardiovascular risk Men or Female ≥ 18 years Patient affiliated to an existing social insurance Exclusion Criteria: 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 The exclusion criterion for all populations except the related population without familial hypercholesterolemia: - 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.
Facility Information:
Facility Name
Le Bocage Hospital
City
Dijon
ZIP/Postal Code
29079
Country
France
Facility Name
CHRU de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Louis Pradel Cardiovascular Hospital
City
Lyon
ZIP/Postal Code
69677
Country
France
Facility Name
La Conception Hospital
City
Marseille
ZIP/Postal Code
13285
Country
France
Facility Name
Nantes University Hospital
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Saint-Antoine Hospital
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Pitié-Salpêtrière Hospital
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Rennes University Hospital
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Toulouse Hospital
City
Toulouse
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia

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