Atherosclerotic DiseaseTELARTANCT02176941
Telomeres and Arterial Aging
An observational study of Atherosclerotic Disease, run by Central Hospital, Nancy, France at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Atherosclerotic Disease
- How many people
- 340 participants
- Where
- 2 sitesFrance
- Study dates
- Jun 2014to Nov 2016
- Phase
- Observational
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Conditions which may impact telomere length:
- Patients undergoing surgery for cancer
- Patients who had had radiotherapy or chemotherapy.
Trial locations and contacts
2 sites in 1 country.
France2 sites, 2 recruiting
- Not yet recruiting
AP Hôpitaux de Marseille
Marseille, 13000
Pascal ROSSI, MD, PhD, +33.4.91.96.89.30, pascalmaurice.rossi@ap-hm.fr
Pascal ROSSI, MD, PhD
- Recruiting
Chu Nancy
Nancy, 54000
Athanase BENETOS, MD, PhD, +33.3.83.15.33.22, a.benetos@chu-nancy.fr
Ghassan WATFA, MD, PhD, +33.3.83.15.33.22, g.watfa@chu-nancy.fr
About this study
Official title: 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:
Read more
- 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.
Read the 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.
- Conditions
- Atherosclerotic Disease
- Keywords
- Telomere Length, Arterial Aging, Endothelial Progenitor Cells, Inflammation, Atherosclerosis
- Medical subject headings
- Inflammation, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Telomere Length (LT) dynamics
TL dynamics: as expressed in the difference between TLs of muscle and leukocytes.
Measured: up to 3 years
Secondary outcomes (2)
Skin telomere length
Measured: up to 3 years
Subcutaneous fat telomere length
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2014 (estimated)
- Study startJun 2014
- Primary completionNov 2016 (estimated)
- Study completionNov 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Atherosclerotic DiseaseStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Collaborators
- National Research Agency, France, Institut National de la Santé Et de la Recherche Médicale, France, Assistance Publique Hopitaux De Marseille, University of Lorraine
- Responsible party
- Sponsor
- Investigators
- Athanase BENETOS, MD, PhD, Principal investigator, Service de Gériatrie et INSERM U1116; Université de Lorraine et CHU de Nancy; France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02176941
- Sponsor's protocol ID
- 2014-A00298-39
- Acronym
- TELARTA
- Status last verified
- Jun 2016
- First submitted
- 26 Jun 2014
- Last updated
- 16 Jun 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 37118904Toupance 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.
PubMed 33955230Benetos 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.
PubMed 29242238
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Telomere in Patients at High Cardiovascular Risk: a Simple Marker or a Major Determinant of Accelerated Arterial Aging
- ClinicalTrials.gov ID
- NCT02176941
- Acronym / sponsor ID
- TELARTA / 2014-A00298-39
- Conditions
- Atherosclerotic Disease
- Keywords
- Telomere Length, Arterial Aging, Endothelial Progenitor Cells, Inflammation, Atherosclerosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 340 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Collaborators
- National Research Agency, France, Institut National de la Santé Et de la Recherche Médicale, France, Assistance Publique Hopitaux De Marseille, University of Lorraine
- Study start
- Jun 2014
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Nov 2016 (estimated)
- First posted
- 27 Jun 2014 (estimated)
- 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 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.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (3 listed)
- Patients undergoing surgery for cancer
- Patients who had had radiotherapy or chemotherapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Telomere Length (LT) dynamics
Time frame: up to 3 years
TL dynamics: as expressed in the difference between TLs of muscle and leukocytes.
2 secondary outcomes
Skin telomere length
Time frame: up to 3 years
Subcutaneous fat telomere length
Time frame: up to 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2016.
- Derived from this study: PubMed 37118904Lai 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.
- Derived from this study: PubMed 33955230Toupance 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.
- Derived from this study: PubMed 29242238Benetos 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.
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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.
Athanase BENETOS, MD, PhD principal investigator
Service de Gériatrie et INSERM U1116; Université de Lorraine et CHU de Nancy; France
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerotic Disease, run by Central Hospital, Nancy, France at 2 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 1 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 16 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Athanase BENETOS, MD, PhD (+33.3.83.15.33.22, a.benetos@chu-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Telomere Length (LT) dynamics (time frame: up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02176941, which also lists 3 linked publications.
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 16 Jun 2016.