Homozygous Familial HypercholesterolemiaSAFIRNCT03234127
Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
A study testing Whole Genome Sequencing in people with Homozygous Familial Hypercholesterolemia, run by Nantes University Hospital at 9 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- Whole Genome Sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 562 participants
- Where
- 9 sitesFrance
- Study dates
- 6 Dec 2017to 6 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 25Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Le Bocage Hospital
Dijon, 29079
CHRU de Lille
Lille, 59037
Louis Pradel Cardiovascular Hospital
Lyon, 69677
La Conception Hospital
Marseille, 13285
Nantes University Hospital
Nantes, 44093
Saint-Antoine Hospital
Paris, 75012
Pitié-Salpêtrière Hospital
Paris, 75013
Rennes University Hospital
Rennes, 35033
Toulouse Hospital
Toulouse, 31059
About this study
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.
Read the 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.
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- Whole Genome Sequencing
- Medical subject headings
- Homozygous Familial Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole Genome SequencingGenetic
Also called Biological analyzes
Whole Genome Sequencing Biomarkers analyses
| Study group | Role | What they receive |
|---|---|---|
| Atherosclerosis- resistance | Other | FH Patient without atherosclerosis Receives: Genetic: Whole Genome Sequencing |
| Control | Other | FH patient with atheroclerosis Receives: Genetic: Whole Genome Sequencing |
| the related population without familial hypercholesterolemia | Other | No FH patient Receives: Genetic: Whole Genome Sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 3 years
Secondary outcomes (6)
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.
Measured: 3 years
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)
Measured: 3 years
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)
Measured: 3 years
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
Measured: 3 years
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
Measured: 3 years
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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2017
- Study start6 Dec 2017
- Primary completion6 May 2021
- Study completion6 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 562 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03234127
- Sponsor's protocol ID
- RC17_0244
- Acronym
- SAFIR
- Status last verified
- May 2021
- First submitted
- 26 Jul 2017
- Last updated
- 24 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of cardiovAscular Contrasted Phenotypes in Patients With FamIliaI hypercholesteRolemia
- ClinicalTrials.gov ID
- NCT03234127
- Acronym / sponsor ID
- SAFIR / RC17_0244
- Conditions
- Homozygous Familial Hypercholesterolemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 562 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 6 Dec 2017 (actual)
- Primary completion
- 6 May 2021 (actual)
- Study completion
- 6 May 2021 (actual)
- First posted
- 31 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Atherosclerosis- resistance | Other | Genetic: Whole Genome SequencingFH Patient without atherosclerosis |
| Control | Other | Genetic: Whole Genome SequencingFH patient with atheroclerosis |
| the related population without familial hypercholesterolemia | Other | Genetic: Whole Genome SequencingNo FH patient |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole Genome SequencingAlso: Biological analyzesWhole Genome Sequencing Biomarkers analyses | Genetic | Atherosclerosis- resistance, Control, the related population without familial hypercholesterolemia |
Primary outcome
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)
6 secondary outcomes
Identification of new biochemical, lipidemic, metabolomic and metagenomic biomarkers associated with cardiovascular protection in FH patients.
Time frame: 3 years
Association of arterial stiffness (reflected by the pulse wave velocity) with the development of coronary atherosclerosis in FH patients
Time frame: 3 years
Association of atherosclerosis of supra-aortic trunks (AST) with the development of coronary atherosclerosis in FH patients
Time frame: 3 years
Association of atherosclerosis of the lower limbs with the development of coronary atherosclerosis (PAD) in FH patients
Time frame: 3 years
Association between aortic valvular score and development of coronary atherosclerosis in FH patients
Time frame: 3 years
Association between coronary calcium score and aortic valvular score in HF patients
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Whole Genome Sequencing in people with Homozygous Familial Hypercholesterolemia, run by Nantes University Hospital at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of genes associated with the resistance to development of coronary atherosclerosis in subjects with heterozygous familial hypercholesterolemia (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2021.