- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02176941
Telomeres and Arterial Aging (TELARTA)
Short Telomere in Patients at High Cardiovascular Risk: a Simple Marker or a Major Determinant of Accelerated Arterial Aging
The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerosis and accelerated aging since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. Our recent results however, indicate that telomere length (TL) is mainly determined at birth and childhood. Since short telomeres ante cede atherosclerosis, the investigators hypothesize that TL is not just a simple marker, but a real determinant of arterial aging. That is because TL reflects cellular repair capacity and a short LTL denotes diminished repair reserves. This hypothesis cannot be tested by measurements of LTL alone, since this parameter reflects TL at birth and its age-dependent attrition thereafter. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues: leukocytes, skeletal muscle, endothelial progenitor cells (EPCs), skin or subcutaneous fat in patients with or without atherosclerosis.
Our model is based on the following premises, which are derived from observations that TL is synchronized (equivalent) across somatic tissues/cells of the newborn:
- TL in skeletal muscle mainly reflects TL at birth
- The difference in TL between muscle and leukocytes in adults (approximately 1.5 Kbp) mainly reflects LTL attrition during the growth period, i.e., childhood/adolescence
- TL in EPCs determines the cell proliferative ability and therefore capacity for vessels repair during aging.
The general aim of the present project is to examine the links of arterial aging with TL, as expressed in different tissues, and LTL dynamics, as expressed in the difference between TLs of muscle and leukocytes.
Study Overview
Status
Conditions
Detailed Description
Specific objectives:
- To determine whether TL during early development, which is primarily reflected in muscle TL, and LTL attrition during development, which is primarily expressed in the difference between muscle TL and LTL, are associated with indices of arterial aging.
To examine the relation between EPC-TL to endothelial regenerative capacity and endothelial function. In order to attain this objective the investigators will perform two types of experiments:
- Measure TL in progenitor cells and relate it to clinical phenotypes of arterial aging and atherosclerosis, as well as markers of endothelial dysfunction
- Generate in vitro progenitor cells with different TL induced by the environmental factors (oxidative stress) and assess their phenotypes concerning inflammation and microvesiculation, in order to show a possible mechanistic relationship between TL in PC and the atherogenic and the regenerative capacities of these cells.
The project is composed of 6 tasks:
T1: Recruitment and sample collection (skeletal muscle, total blood) of 170 patients with atherosclerosis and 170 controls. Performed by surgeons and cardiologists of Marseille and Nancy University hospitals T2: Characterization of arterial aging in all patients (Geriatric Dpt, Univ. hospital Nancy, Pr Benetos and AP-HM, Internal Medicine, Marseille, Dr Rossi) T3: Characterization of early and late endothelial progenitor cells (EPC): laboratory of hematology and vascular biology and in UMR_S1076 in Marseille (Prs Dignat-George and Sabatier) T4: Measurements of TL in all samples (skeletal muscle, leukocytes and EPC): UMR_S1116 Nancy (Dr Lacolley) in collaboration with Pr Aviv (University of Medicine of New Jersey) T5: Characterization of inflammation markers in blood samples: UMR_S1116 and the UMR_S1122 (Dr Siest-Visvikis, Nancy) T6: Database construction and statistical analyses (UMR_S1116)
The results of this program could completely modify the present concept on the association between TL and cardiovascular risk: Actually, if our concept of early determination of TL is valid, therefore TL could be a true determinant of the arterial aging pace, through limitation of repair capacity of cells.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
-
-
-
Marseille, France, 13000
- Not yet recruiting
- AP Hôpitaux de Marseille
-
Contact:
- Pascal ROSSI, MD, PhD
- Phone Number: +33.4.91.96.89.30
- Email: pascalmaurice.rossi@ap-hm.fr
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Principal Investigator:
- Pascal ROSSI, MD, PhD
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Nancy, France, 54000
- Recruiting
- CHU Nancy
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Contact:
- Athanase BENETOS, MD, PhD
- Phone Number: +33.3.83.15.33.22
- Email: a.benetos@chu-nancy.fr
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Contact:
- Ghassan WATFA, MD, PhD
- Phone Number: +33.3.83.15.33.22
- Email: g.watfa@chu-nancy.fr
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Principal Investigator:
- Athanase BENETOS, MD, PhD
-
Sub-Investigator:
- Ghassan WATFA, MD, PhD
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Sub-Investigator:
- Sylvie GAUTIER, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Men and women, aged ≥ 20 years who are admitted for different types of surgery or for pacemaker/ defibrillator implantation and provide informed consent for participating in this study.
Exclusion Criteria:
Conditions which may impact telomere length:
- Patients undergoing surgery for cancer
- Patients who had had radiotherapy or chemotherapy.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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ATHEROMA group
"ATHEROMA" group will include patients undergoing cardiovascular surgery or have pacemaker/defibrillator implantation and have a clinically significant atherosclerotic disease
|
Control Surgery group
"Control Surgery" group will include patients undergoing other surgery or pacemaker/defibrillator implantation without evidence of clinical CV disease or history of previous CV disease.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Telomere Length (LT) dynamics
Time Frame: up to 3 years
|
TL dynamics: as expressed in the difference between TLs of muscle and leukocytes.
|
up to 3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Skin telomere length
Time Frame: up to 3 years
|
up to 3 years
|
Subcutaneous fat telomere length
Time Frame: up to 3 years
|
up to 3 years
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measure TL in progenitor cells
Time Frame: up to 3 years
|
up to 3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Athanase BENETOS, MD, PhD, Service de Gériatrie et INSERM U1116; Université de Lorraine et CHU de Nancy; France
Publications and helpful links
General Publications
- Toupance S, Simonici S, Labat C, Dumoulin C, Lai TP, Lakomy C, Regnault V, Lacolley P, Dignat George F, Sabatier F, Aviv A, Benetos A; TELARTA consortium dagger. Number and Replating Capacity of Endothelial Colony-Forming Cells are Telomere Length Dependent: Implication for Human Atherogenesis. J Am Heart Assoc. 2021 May 18;10(10):e020606. doi: 10.1161/JAHA.120.020606. Epub 2021 May 6.
- Benetos A, Toupance S, Gautier S, Labat C, Kimura M, Rossi PM, Settembre N, Hubert J, Frimat L, Bertrand B, Boufi M, Flecher X, Sadoul N, Eschwege P, Kessler M, Tzanetakou IP, Doulamis IP, Konstantopoulos P, Tzani A, Korou M, Gkogkos A, Perreas K, Menenakos E, Samanidis G, Vasiloglou-Gkanis M, Kark JD, Malikov S, Verhulst S, Aviv A. Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model. Circ Res. 2018 Feb 16;122(4):616-623. doi: 10.1161/CIRCRESAHA.117.311751. Epub 2017 Dec 14.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 2014-A00298-39
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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