Atherosclerosis of ArteryPROGENTELARTNCT03928769
PROGENitors, TELomeres and ARTerial Aging
An observational study of Atherosclerosis of Artery, run by Central Hospital, Nancy, France at 1 site in France.
Trial summary
The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ACVD) 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 18 years and older
- Conditions the study is for
- Atherosclerosis of Artery
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 8 May 2019to 20 Oct 2021
- How long will I take part?
- 1 Day
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Recruitment is expected in patients undergoing surgery giving access to arterial surgical residues. Recruiter Service: Vascular Surgery at Nancy-Brabois University Hospital (Prof. Serguei Malikov) As part of the clinical care, the samples available according to the groups are as follows: * for the group suffering from atheromatous pathology: lesion (pathological zone) and lesion border (healthy zone) * for the group with traumatic vascular injury: lesion (but non-atheromatous lesion, therefore considered as control) and lesion border.
Who may be able to join
- Male or female ≥ 18 years
- Patient for whom a vascular surgery is programmed, and whose nature allows obtaining of arterial segment without any harm for the health of the patient
- Patient for whom a blood sample is planned on the day of the procedure
- Person who has received complete information on the organization of the research and who has not objected to his participation and the exploitation of his data
- Compulsory affiliation to social security
Who cannot join
- Patient who has previously undergone radiotherapy at the sampling site
- Patient with cancer at the sampling site
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Telomere Length in Arterial Smooth Muscle Cells and Circulating/Tissue Endothelial Progenitors in the Development of Atherosclerotic Lesions: Set up of the Experimental Model
The prevailing view in telomere epidemiology is that leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ACVD) since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. However, our recent results indicate that telomere length (TL) is mainly determined before adulthood, by TL at birth and TL attrition during growth. They also demonstrate that short telomeres precede the clinical manifestation of atherosclerosis. The investigators therefore hypothesize that LT is not a simple marker, but a major determinant of arterial aging.
Two mechanistic hypotheses may explain an active role of short telomeres in accelerated arterial aging and development of ACVD.
Read more
The first is that a short TL at the leukocyte level reflects a short TL in endothelial progenitor cells (EPC). Cell replicative capacity being TL-dependent, short telomeres in the EPC would therefore be responsible for diminished replication capacity and vascular repair potential, thereby increasing the vulnerability for developing age-related arterial diseases.
The second hypothesis is that a short LTL reflects short TL in arterial wall cells, leading to an increase in the number of senescent vascular cells. Senescent cells are known to alter their secretion pattern, a phenomenon called senescence-associated secretory phenotype (SASP), and thus contribute to tissue injury by promoting inflammation and tissue remodeling leading to lesion progression.
These assumptions cannot be tested by LTL measurements alone. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues and cell types: leukocytes, circulating EPCs, in situ EPCs and arterial resident cells (mainly smooth muscle cells) in patients with or without atherosclerosis.
Our model is based on the following observations:
- TL is synchronized (equivalent) across somatic tissues/cells of the newborn: an individual with short telomeres (relative to his pairs) in one tissue should also have short telomeres (relative to his pairs) in other tissues.
- TL in EPCs (both circulating and in situ) determines the cell proliferative ability and therefore capacity for vessels repair during aging.
- TL in the cells of the arterial wall determines the number of senescent cells that therefore contribute to tissue injury through their change of phenotype.
The general aim of the present project is to examine the mechanistic links between arterial aging and TL in these different cell types.
- Conditions
- Atherosclerosis of Artery
- Keywords
- Telomere length, Endothelial progenitor cell, Smooth muscle cell, Senescence
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 |
|---|---|---|
| Control Group | Patients with traumatic vascular injury, ultimately corresponding to control patients | |
| Atheroma Group | Patients will be included either in the atheromatous group (patients with atheromatous pathology) or in the control group (patients without atheromatous pathology), according to the clinical evaluation. In the atheromatous group, subjects must have a clinically significant atheromatous pathology. The investigator must specify the site (s) affected by the atheroma: carotid artery, coronary artery, aorta, renal artery, mesenteric artery or lower limb artery. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating EPC levels
Circulating EPC levels measured from whole blood specimens after primary culture of peripheral blood mononuclear cells (PBMC) on fibronectin (in cells per million of PBMCs)
Measured: Inclusion visit
Tissue EPC levels
Tissue EPC levels measured from arterial wall cells in healthy and pathological zones obtained after enzymatic digestion, cell sorting and primary culture.
Measured: Inclusion visit
Secondary outcomes (1)
TL in EPC
Description and comparison of telomere lengths in circulating and tissue endothelial progenitors in patients with atheromatous pathology and those with traumatic vascular disease.
The telomere length in the different cell types (expressed in kb) will be measured by Southern blot after DNA extraction.
Measured: Inclusion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2019
- Study start8 May 2019
- Primary completion20 Apr 2021 (estimated)
- Study completion20 Oct 2021 (estimated)
Why it stopped: Covid-19 Pandemics
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atherosclerosis of ArteryStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- 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
- 100 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03928769
- Sponsor's protocol ID
- 2019-A00143-54
- Acronym
- PROGENTELART
- Status last verified
- Jan 2021
- First submitted
- 24 Apr 2019
- Last updated
- 15 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Telomere Length in Arterial Smooth Muscle Cells and Circulating/Tissue Endothelial Progenitors in the Development of Atherosclerotic Lesions: Set up of the Experimental Model
- ClinicalTrials.gov ID
- NCT03928769
- Acronym / sponsor ID
- PROGENTELART / 2019-A00143-54
- Conditions
- Atherosclerosis of Artery
- Keywords
- Telomere length, Endothelial progenitor cell, Smooth muscle cell, Senescence
- Study type
- Observational
- Recruitment status
- SuspendedReason stopped: Covid-19 Pandemics
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 8 May 2019 (actual)
- Primary completion
- 20 Apr 2021 (estimated)
- Study completion
- 20 Oct 2021 (estimated)
- First posted
- 26 Apr 2019 (actual)
- 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 atherosclerotic cardiovascular disease (ACVD) since it serves as a biomarker of the cumulative burden of inflammation and oxidative stress during adult life. However, our recent results indicate that telomere length (TL) is mainly determined before adulthood, by TL at birth and TL attrition during growth. They also demonstrate that short telomeres precede the clinical manifestation of atherosclerosis. The investigators therefore hypothesize that LT is not a simple marker, but a major determinant of arterial aging.
Two mechanistic hypotheses may explain an active role of short telomeres in accelerated arterial aging and development of ACVD.
The first is that a short TL at the leukocyte level reflects a short TL in endothelial progenitor cells (EPC). Cell replicative capacity being TL-dependent, short telomeres in the EPC would therefore be responsible for diminished replication capacity and vascular repair potential, thereby increasing the vulnerability for developing age-related arterial diseases.
The second hypothesis is that a short LTL reflects short TL in arterial wall cells, leading to an increase in the number of senescent vascular cells. Senescent cells are known to alter their secretion pattern, a phenomenon called senescence-associated secretory phenotype (SASP), and thus contribute to tissue injury by promoting inflammation and tissue remodeling leading to lesion progression.
These assumptions cannot be tested by LTL measurements alone. The investigators propose, therefore, a model that makes it possible to examine different elements of TL dynamics in different tissues and cell types: leukocytes, circulating EPCs, in situ EPCs and arterial resident cells (mainly smooth muscle cells) in patients with or without atherosclerosis.
Our model is based on the following observations:
- TL is synchronized (equivalent) across somatic tissues/cells of the newborn: an individual with short telomeres (relative to his pairs) in one tissue should also have short telomeres (relative to his pairs) in other tissues.
- TL in EPCs (both circulating and in situ) determines the cell proliferative ability and therefore capacity for vessels repair during aging.
- TL in the cells of the arterial wall determines the number of senescent cells that therefore contribute to tissue injury through their change of phenotype.
The general aim of the present project is to examine the mechanistic links between arterial aging and TL in these different cell types.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Group | – | –Patients with traumatic vascular injury, ultimately corresponding to control patients |
| Atheroma Group | – | –Patients will be included either in the atheromatous group (patients with atheromatous pathology) or in the control group (patients without atheromatous pathology), according to the clinical evaluation. In the atheromatous group, subjects must have a clinically significant atheromatous pathology. The investigator must specify the site (s) affected by the atheroma: carotid artery, coronary artery, aorta, renal artery, mesenteric artery or lower limb artery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Recruitment is expected in patients undergoing surgery giving access to arterial surgical residues. Recruiter Service: Vascular Surgery at Nancy-Brabois University Hospital (Prof. Serguei Malikov) As part of the clinical care, the samples available according to the groups are as follows: * for the group suffering from atheromatous pathology: lesion (pathological zone) and lesion border (healthy zone) * for the group with traumatic vascular injury: lesion (but non-atheromatous lesion, therefore considered as control) and lesion border.
Key inclusion criteria (5 listed)
- Male or female ≥ 18 years
- Patient for whom a vascular surgery is programmed, and whose nature allows obtaining of arterial segment without any harm for the health of the patient
- Patient for whom a blood sample is planned on the day of the procedure
- Person who has received complete information on the organization of the research and who has not objected to his participation and the exploitation of his data
- Compulsory affiliation to social security
Key exclusion criteria (2 listed)
- Patient who has previously undergone radiotherapy at the sampling site
- Patient with cancer at the sampling site
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
Circulating EPC levels
Time frame: Inclusion visit
Circulating EPC levels measured from whole blood specimens after primary culture of peripheral blood mononuclear cells (PBMC) on fibronectin (in cells per million of PBMCs)
Tissue EPC levels
Time frame: Inclusion visit
Tissue EPC levels measured from arterial wall cells in healthy and pathological zones obtained after enzymatic digestion, cell sorting and primary culture.
1 secondary outcome
TL in EPC
Time frame: Inclusion visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2021.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis of Artery, run by Central Hospital, Nancy, France at 1 site 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 5 inclusion and 2 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: paused, as of the sponsor's last update on 15 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Circulating EPC levels (time frame: Inclusion visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Apr 2021.