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

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ClinicalTrials.gov Identifier: NCT03234127
Recruitment Status : Completed
First Posted : July 31, 2017
Last Update Posted : May 24, 2021
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Homozygous Familial Hypercholesterolemia Genetic: Whole Genome Sequencing Not Applicable

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 562 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Actual Study Start Date : December 6, 2017
Actual Primary Completion Date : May 6, 2021
Actual Study Completion Date : May 6, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Atherosclerosis- resistance
FH Patient without atherosclerosis
 Genetic: Whole Genome Sequencing
Whole Genome Sequencing Biomarkers analyses
Other Name: Biological analyzes
Control
FH patient with atheroclerosis
 Genetic: Whole Genome Sequencing
Whole Genome Sequencing Biomarkers analyses
Other Name: Biological analyzes
the related population without familial hypercholesterolemia
No FH patient
 Genetic: Whole Genome Sequencing
Whole Genome Sequencing Biomarkers analyses
Other Name: Biological analyzes


Outcome Measures
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Primary Outcome Measures :
  1. Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia [ Time Frame: 3 years ]
    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 :
  1. Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients. [ Time Frame: 3 years ]
    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.

  2. Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients [ Time Frame: 3 years ]
    Measurement of arterial stiffness measured by popmeter® (pulse wave velocity)

  3. Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients [ Time Frame: 3 years ]
    Measurement of ASD through arterial Doppler ultrasonography (Intra-media thickness (IMT), degree of stenosis (ESCT), plaque)

  4. Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients [ Time Frame: 3 years ]
    Measurement of lower extremity involvement by arterial doppler ultrasonography

  5. Association between aortic valvular score and development of coronary atherosclerosis in FH patients [ Time Frame: 3 years ]
    Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan

  6. Association between coronary calcium score and aortic valvular score in HF patients [ Time Frame: 3 years ]
    Measurement of coronary calcium score and aortic valvular score (optional) by a thoracic CT scan


Eligibility Criteria
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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03234127


Locations
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France
Le Bocage Hospital
Dijon, France, 29079
CHRU de Lille
Lille, France, 59037
Louis Pradel Cardiovascular Hospital
Lyon, France, 69677
La Conception Hospital
Marseille, France, 13285
Nantes University Hospital
Nantes, France, 44093
Saint-Antoine Hospital
Paris, France, 75012
Pitié-Salpêtrière Hospital
Paris, France, 75013
Rennes University Hospital
Rennes, France, 35033
Toulouse Hospital
Toulouse, France, 31059
Sponsors and Collaborators
Nantes University Hospital
More Information
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT03234127    
Other Study ID Numbers: RC17_0244
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: May 24, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
 Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias