Identification of CETP as a Marker of Atherosclerosis

NCT02081066 | Completed

• 2 other identifiers: C13-202013-A00798-37
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

The reverse cholesterol transport (RCT) pathway, which involves the centripetal movement of free cholesterol from peripheral tissues, including the vessel wall, to the liver represent the primary mechanism by which HDL protects against atherosclerosis and by which it may induce plaque regression. Recent data reveal that the capacity of HDL to efflux cholesterol from macrophages, a metric of HDL function reflecting the initial step of the RCT, is clinically relevant, displaying a strong inverse association with both carotid intima-media thickness and the severity of angiographic CAD; such observations were independent of HDL-C levels. In human, the Cholesteryl Ester Transfer Protein (CETP), represents a key protein of the RCT pathway and mediates redistribution of neutral lipids between lipoproteins, has been identified as a potential therapeutic target against atherosclerosis. It is known that CETP activity correlates with HDL-C levels and represents a key modulator of the ability of whole plasma to mediate free cholesterol efflux from human macrophages. Recent studies showed that 23% of endogenous plasma CETP activity variability is explained by plasma LDL-C (12.0%), HDL-C (6.4%) and TG (4.4%) whereas sex and BMI accounted together for only 0.7% of its variability. Scoring patients for cardiovascular risk on the basis of their plasma lipid levels (TC, TG, LDL-C and HDL-C), revealed that patients with high cardiovascular risk (score ≥3) displayed a mean endogenous plasma CETP activity above 34%. Therefore plasma CETP activity represents a potent indicator of cardiovascular risk in patients with metabolic disorders since it integrates major independent risk factors. The objective of this study is to decipher the relationship between CETP, HDL efflux capacity and the development of atherosclerosis in humans in order to identify CETP as a potent biomarker of atherosclerosis distribution.

Conditions

Cardiovascular Disease

Outcome Measures

Primary Outcomes (3)

• Endogenous CETP activity

  Day 1

• carotid intima-media thickness

  day 1

• Coronary calcium score

  Day 1

Secondary Outcomes (2)

• plasma efflux capacity from human macrophage

  Day 1

• HDL genetic variant

  Day1

Study Arms (1)

patients with cardiovascular risk factors

OTHER

Other: cardiovascular risk factors

Interventions

cardiovascular risk factors OTHER

patients with cardiovascular risk factors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to initiation of the study
• Men and women aged 18 or more years
• Patients displaying at least one abnormal plasma lipid parameter and/or receiving a lipid-lowering therapy unchanged for at least 3 months.

You may not qualify if:

• Current significant renal disease, including: nephrotic syndrome; chronic renal failure and/or serum creatinine \>1.7 x upper limit of the reference range (ULRR)
• Uncontrolled hypothyroidism defined as TSH \>2 x ULRR
• Active hepatobiliary disease, including chronic hepatitis B or hepatitis C infection (confirmed by serology); or an aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) \>3.0 x ULRR
• Any prior history of malignancy or current cancer
• Current chronic or acute inflammatory syndrome defined as CRP\>10 mg/l

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (1)

Inserm Umrs1166

Paris, 75013, France

Location

Related Publications (1)

• Le Roy T, Lecuyer E, Chassaing B, Rhimi M, Lhomme M, Boudebbouze S, Ichou F, Haro Barcelo J, Huby T, Guerin M, Giral P, Maguin E, Kapel N, Gerard P, Clement K, Lesnik P. The intestinal microbiota regulates host cholesterol homeostasis. BMC Biol. 2019 Nov 27;17(1):94. doi: 10.1186/s12915-019-0715-8.

  PMID: 31775890 RESULT

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Heart Disease Risk Factors

Intervention Hierarchy (Ancestors)

Risk Factors; Risk; Probability; Statistics as Topic; Epidemiologic Methods; Investigative Techniques; Causality; Epidemiologic Factors; Quality of Health Care; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms; Public Health; Environment and Public Health

Study Officials

• Maryse Guerin, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2014
• First Posted: March 7, 2014
• Study Start: September 25, 2014
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: April 24, 2026

Record last verified: 2021-08

Locations

FR (1)