NCT02176941

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
340

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Jun 2014

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2014

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

June 26, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 27, 2014

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

June 16, 2016

Status Verified

June 1, 2016

Enrollment Period

2.4 years

First QC Date

June 26, 2014

Last Update Submit

June 15, 2016

Conditions

Atherosclerotic Disease

Keywords

Telomere LengthArterial AgingEndothelial Progenitor CellsInflammationAtherosclerosis

Outcome Measures

Primary Outcomes (1)

  • Telomere Length (LT) dynamics

    TL dynamics: as expressed in the difference between TLs of muscle and leukocytes.

    up to 3 years

Secondary Outcomes (2)

  • Skin telomere length

    up to 3 years

  • Subcutaneous fat telomere length

    up to 3 years

Other Outcomes (1)

  • Measure TL in progenitor cells

    up to 3 years

Study Arms (2)

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.

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Individuals will be recruited among patients admitted to the hospital either for surgery or for installing pacemakers/ defibrillators. Informed consent will be signed at the beginning of the hospitalization.

You may qualify if:

  • 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.

You may not qualify if:

  • Conditions which may impact telomere length:
  • Patients undergoing surgery for cancer
  • Patients who had had radiotherapy or chemotherapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

AP Hôpitaux de Marseille

Marseille, 13000, France

NOT YET RECRUITING

Chu Nancy

Nancy, 54000, France

RECRUITING

Related Publications (3)

  • Lai TP, Verhulst S, Savage SA, Gadalla SM, Benetos A, Toupance S, Factor-Litvak P, Susser E, Aviv A. Buildup from birth onward of short telomeres in human hematopoietic cells. Aging Cell. 2023 Jun;22(6):e13844. doi: 10.1111/acel.13844. Epub 2023 Apr 28.

    PMID: 37118904DERIVED

  • 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.

    PMID: 33955230DERIVED

  • 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.

    PMID: 29242238DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Skeletal Muscle, skin, fat (as surgical waste) and Blood sampling DNA extractions and telomere length measurements (Southern) in muscular cells, white blood cells and endothelial progenitor cells. Determination, isolation and characterization of endothelial progenitor cells Microparticle (MP) von Willebrand Factor : vWF, CD146, CD31 Tissue plasminogen activator/plasminogen activator inhibitor-1 complexes thrombomodulin, endothelial protein C receptor, free tissue factor pathway inhibitor sirtuin proteins Biological phenotyping of inflammatory factors in plasma : IL2, IL4, IL6, IL8, IL10, VEGF, IFNG, TNFA, IL1A, IL1B, MCP1, EGF, CRP, Haptoglobine

MeSH Terms

Conditions

InflammationAtherosclerosis

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Athanase BENETOS, MD, PhD

    Service de Gériatrie et INSERM U1116; Université de Lorraine et CHU de Nancy; France

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Athanase BENETOS, MD, PhD

CONTACT

+33.3.83.15.33.22a.benetos@chu-nancy.fr

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 26, 2014

First Posted

June 27, 2014

Study Start

June 1, 2014

Primary Completion

November 1, 2016

Study Completion

November 1, 2016

Last Updated

June 16, 2016

Record last verified: 2016-06

Locations

FR(2)