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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 : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Tracking Information
First Submitted Date  ICMJE July 26, 2017
First Posted Date  ICMJE July 31, 2017
Last Update Posted Date June 9, 2020
Actual Study Start Date  ICMJE December 6, 2017
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2019)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
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)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2017)
  • 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.
  • 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)
  • 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)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
Official Title  ICMJE Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Homozygous Familial Hypercholesterolemia
Intervention  ICMJE Genetic: Whole Genome Sequencing
Whole Genome Sequencing Biomarkers analyses
Other Name: Biological analyzes
Study Arms  ICMJE
  • Atherosclerosis- resistance
    FH Patient without atherosclerosis
    Intervention: Genetic: Whole Genome Sequencing
  • Control
    FH patient with atheroclerosis
    Intervention: Genetic: Whole Genome Sequencing
  • the related population without familial hypercholesterolemia
    No FH patient
    Intervention: Genetic: Whole Genome Sequencing
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 8, 2020)
600
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2017)
800
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03234127
Other Study ID Numbers  ICMJE RC17_0244
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Nantes University Hospital
Study Sponsor  ICMJE Nantes University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nantes University Hospital
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP