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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 : Not yet recruiting
First Posted : July 31, 2017
Last Update Posted : October 6, 2017
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.


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
Estimated Study Start Date : October 15, 2017
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : October 31, 2019

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




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)


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



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Ages Eligible for Study:   45 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.
  • Patient with a coronary calcium score
  • Men ≥ 45 years of age; Female ≥ 55 years
  • Patient affiliated to an existing social insurance

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

  • Subjects for secondary prevention of a coronary event or ischemic heart disease, irrespective of the result of the coronary calcium score
  • 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, PAD) with: For women between 55 and 65 years, a calcium score * For women over 65 years old, a calcium score * ≤ 10 Agatston units For men between 45 and 55 years old, a calcium score * For men over 55 years old, a calcium score * ≤ 10 Agatston units

* Less than 5 years

Exclusion Criteria:

  • Subject suffering from cancer or progressive neoplasia
  • Subjects who underwent radiotherapy covering the cardiac field
  • Subject treated with recent corticosteroid therapy
  • Subjects with unsubstituted or poorly controlled hypothyroidism (TSH> normal)
  • Subject of the Human Immunodeficiency Virus (HIV)
  • Subject receiving immunosuppressive or anti-cancer treatment
  • Subject refusing to participate
  • Subjects under tutelage, curatorship or a safeguard of justice or without social insurance

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
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
France
Le Bocage Hospital Not yet recruiting
Dijon, France, 29079
Contact: Yves COTTIN, Pr    03.80.28.12.55    yves.cottin@chu-dijon.fr   
Principal Investigator: Yves COTTIN, Pr         
Louis Pradel Cardiovascular Hospital Not yet 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 Not yet 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 Not yet 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 Not yet 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 Not yet 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 Not yet 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 Not yet 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

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 6, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipoproteinemia Type II
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias