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Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous (FH-CALC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03501875
Recruitment Status : Active, not recruiting
First Posted : April 18, 2018
Last Update Posted : February 5, 2020
Institute of Cardiometabolism and Nutrition, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by elevated plasma levels of LDL-C cholesterol. This early and significant elevation of LDL-C triggers premature atherosclerosis, particularly coronary artery disease.

The initiation and management of LDL-C therapies is based on cardiovascular risk assessment. Although this is undoubtedly higher than in normocholesterolemic patients, a significant heterogeneity in heFH patients still persists that is not completely explained. Moreover, the evaluation of cardiovascular risk in patients with heFH is difficult for many reasons: non-validity of risk scores, futility of a risk calculation limited to 10 years in a young patient, late positivity of stress tests .

Therefore, there is a clear need for new cardiovascular risk assessment tools to identify higher risk heFH patients who could benefit from early and aggressive treatment.

The Coronary Artery Calcium (CAC) Score has been widely studied in the US and validated in European recommendations, and has shown the best reclassification index for patients at intermediate cardiovascular risk. A CAC score of zero is associated with a very low risk of event irrespective of the number of risk factors.

Non-calcified plaques are by definition not detected by ACC and patients with CAC = 0 may only have soft non-calcified plaques. The prevalence of these non-calcified plaques in very high-risk patients with acute coronary syndrome is 5%. The prevalence in FH patients is unknown. It has also been shown that the extent of the atherosclerotic burden is related to cardiovascular risk.

CAC score has been poorly evaluated in heFH patients. However, hypercholesterolemia and calcifications have been shown to be correlated: supra-aortic calcified masses in homozygous FH patients, early calcifications associated with chronic exposure to high LDL-C (cholesterol burden, equivalent to cigarettes) and finally, the calcifying role of statins.

The early increase of LDL-C in patients with genetic forms of FH causes premature cardiovascular damage. Investigators' hypothesis is that patients with FH have earlier coronary atheroma (and thus calcifications and non-calcified plaques) due to exposure early in life to high levels of LDL-cholesterol.

Condition or disease Intervention/treatment Phase
Familial Hypercholesterolemia - Heterozygous Radiation: CAC Score Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Study of Coronary Calcification in Subjects With Autosomal Dominant Familial Hypercholesterolemia Heterozygous
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : February 1, 2021
Estimated Study Completion Date : May 1, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: CAC Score
CAC Score evaluated by the Agatston method
Radiation: CAC Score
Computed tomography angiography (CTA) with an injection of iodine-rich contrast material

Primary Outcome Measures :
  1. Coronary Artery Calcium evaluated by Agatston Score [ Time Frame: one day ]
    Calcium Score

Secondary Outcome Measures :
  1. Cholesterol burden [ Time Frame: one day ]
    Total and LDL cholesterol before treatment (at diagnosis) (age at diagnosis) + yearly total and LDL-cholesterol on treatment (after diagnosis)

  2. Coronary atheromatous plaque [ Time Frame: one day ]
    Coronary computed tomography angiography: evaluation of atherosclerotic load according to the CAD-RADS classification

  3. Peripheral atherosclerotic burden [ Time Frame: one day ]
    Carotid and femoral intima-media thickness

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients with a heterozygous form of familial hypercholesterolemia:

  • Aged 35 to 60 years old.
  • Asymptomatic.
  • No sign of ischemia with ECG.
  • No personal history of coronary heart disease.
  • Treated or untreated by cholesterol lowering treatment.
  • Prior clinical examination performed
  • Beneficiary of a social protection scheme or beneficiary (excluding AME)
  • Informed patient and signed consent form

Exclusion Criteria:

  • Person under tutorship or curatorship, or unable to give consent
  • Pregnancy, breastfeeding, woman of childbearing potential in the absence of effective contraception - a urine pregnancy test will be done in hospital on the day of the coroscanner
  • Contraindication to CT or injection of iodinated contrast medium or injection of esmolol hydrochloride
  • Technical counter-indication: patient diameter> 70 cm, weight> 250 kg
  • Renal insufficiency (CL <60)
  • Personal history of cardiovascular disease and myocardial infarction
  • Type 2 diabetes or uncontrolled diabetes mellitus for more than 5 years
  • Uncontrolled hypertension
  • Atrial fibrillation, ventricular arrhythmia
  • Participation in another interventional research involving the human person or being in the exclusion period following previous research involving the human person, if applicable

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 identifier (NCT number): NCT03501875

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Hôpital Pitié-Salpêtrière
Paris, France, 75013
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Institute of Cardiometabolism and Nutrition, France
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Principal Investigator: Antonio GALLO, Dr Hôpital Pitié-Salpêtrière, APHP
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Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT03501875    
Other Study ID Numbers: P170703J
2017-A02904-49 ( Registry Identifier: ID-RCB )
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020

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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
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn