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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 : Recruiting
First Posted : July 31, 2017
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 800 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
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


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




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



Information from the National Library of Medicine

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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.


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


Contacts
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Contact: Matthieu PICHELIN 02 53 48 27 06 matthieu.pichelin@univ-nantes.fr
Contact: Bertrand CARIOU, Pr 02.53.48.27.07 bertrand.cariou@univ-nantes.fr

Locations
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France
Le Bocage Hospital Recruiting
Dijon, France, 29079
Contact: Yves COTTIN, Pr    03.80.28.12.55    yves.cottin@chu-dijon.fr   
Principal Investigator: Yves COTTIN, Pr         
CHRU de Lille Not yet recruiting
Lille, France, 59037
Contact: Cécile YELNIK    0320445479    cecile.yelnik@chru-lille.fr   
Principal Investigator: Cécile YELNIK         
Louis Pradel Cardiovascular Hospital Recruiting
Lyon, France, 69677
Contact: Philippe MOULIN, Pr    04.72.68.13.04    philippe.moulin@chu-lyon.fr   
Principal Investigator: Philippe MOULIN, Pr         
La Conception Hospital Recruiting
Marseille, France, 13285
Contact: Sophie BELIARD, Dr    04.91.38.36.50    Sophie.BELIARD@ap-hm.fr   
Principal Investigator: Sophie BELIARD, Dr         
Nantes University Hospital Recruiting
Nantes, France, 44093
Contact: Bertrand CARIOU, Pr    02.53.48.27.07    bertrand.cariou@univ-nantes.fr   
Principal Investigator: Bertrand CARIOU, Pr         
Saint-Antoine Hospital Recruiting
Paris, France, 75012
Contact: Franck BOCCARA, Dr    01.49.28.24.49    franck.boccara@aphp.fr   
Principal Investigator: Franck BOCCARA, Dr         
Pitié-Salpêtrière Hospital Recruiting
Paris, France, 75013
Contact: Eric BRUCKERT, Pr    01.42.17.57.85    eric.bruckert@aphp.fr   
Principal Investigator: Eric BRUCKERT, Pr         
Rennes University Hospital Recruiting
Rennes, France, 35033
Contact: François PAILLARD, Dr    02.99.28.25.40    francois.paillard@chu-rennes.fr   
Principal Investigator: François PAILLARD, Dr         
Toulouse Hospital Recruiting
Toulouse, France, 31059
Contact: Jean FERRIERES, Pr    05.61.32.33.39    ferrieres.j@chu-toulouse.fr   
Principal Investigator: Jean FERRIERES, Pr         
Sponsors and Collaborators
Nantes University Hospital

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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT03234127     History of Changes
Other Study ID Numbers: RC17_0244
First Posted: July 31, 2017    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: July 2019
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