Myocardial InfarctionCHATHNCT04581057
Correlation Between Clonal Hematopoiesis, Cardio-vascular Events, Inflammation and Atherosclerosis
A study testing Specific blood sampling in people with Myocardial Infarction, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
This study aims at evaluating the prevalence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients over 75 presenting with a first cardio-vascular event (CVE). The investigators will also determine if CHIPs are more frequent in this population compared to a control cohort without CVE. Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Myocardial Infarction
- What is being tested?
- Specific blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 1 siteFrance
- Study dates
- 23 Jun 2020to 3 Oct 2021
- Phase
- Interventional
- 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 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients (male or female) over 75 years old
- Patients with a first CVE (myocardial infarction) of atheromatous origin that occurred between 2 and 7 months before inclusion
- Absence of evidence of hematological malignancy (known or obvious by the results of blood counts)
- Subject registered with a social security scheme
- Written informed consent obtained
Who cannot join
- Patients who did not presented any CVE in the last 7 months
- Patients with CVE with a non-atheromatous origin (dissection, embolic, …)
- Presence of an unbalanced diabetes (defined as HbA1C > 10%)
- History of previous CVE before 75 year-old : myocardial infarction, stroke of atheromatous origin
- Hematological malignancy (known or obvious on the results of blood counts)
- Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases).
Show all 16Show fewer
- Long term anti-inflammatory treatments:
- Corticoids
- Nonsteroidal anti-inflammatory drugs
- Aspirin (> 325 mg per day)
- Cyclo-oxygenase II inhibitors
- Persons under judicial safeguards, trustee or curators
- Person deprived of judicial or administrative freedom
- Person unable to give her consent
- Non-cooperative person
- Exclusion period after another clinical study or participation to another interventional clinical study testing a drug in the 30 days before inclusion
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Frequency of Clonal Hematopoiesis in Patients Over 75 With a First Cardio Vascular Event. Consequences on Inflammation and Atherosclerosis
This study aims at evaluating the prevalence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients over 75 presenting with a first cardio-vascular event (CVE). The investigators will also determine if CHIPs are more frequent in this population compared to a control cohort without CVE. An association between CHIP, a systemic inflammation and increased atherosclerosis will also be assessed.
Read the detailed description
Despite increasing knowledge on the pathophysiology of cardio-vascular diseases (in particular the role of inflammation in the development of atherosclerosis), predicting their occurrence remains largely difficult. Aging remains the most powerful factor for predicting the occurrence of myocardial infarction, independently from other identified risk factors. Few years ago, acquired mutations were described in the hematopoietic system of apparently healthy subjects. This phenomenon, now described as CHIP (Clonal Hematopoiesis of Indeterminate Potential) is more frequently observed in elderly people, and has been recently linked to an increased risk of cardio-vascular events. Experiments in mice demonstrated that these CHIPs are responsible for an inflammation that supports the development of atherosclerosis. However the link between CHIP, inflammation and atherosclerosis has never been demonstrated in humans.
In this study, the investigators will search for an increased frequency of CHIP in patients with a first cardio-vascular event (CVE). Seven months after the CVE, a blood sample will be taken. Mutations in the 9 most frequently mutated genes in CHIP will be evaluated by Next Generation Sequencing. Systemic inflammation will be evaluated by measurement of circulating levels of CRP, IL-1β, IL-6, IL-10 and TNF-α. Atherosclerosis will be evaluated via the volume of atherosclerotic plaques as assessed by 3D ultrasound analysis. The presence of CHIP will be correlated to traditional cardiovascular risk factors, systemic inflammation markers and the level of atherosclerosis. The investigators will also assess the relationship between the presence of CHIP and the risk of CVE reoccurrence.
- Conditions
- Myocardial Infarction
- Being tested
- Specific blood sampling
- Keywords
- CHIP, Cardiovascular events, Atherosclerosis, Inflammation
- Medical subject headings
- Myocardial Infarction, Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Specific blood samplingBiological
A 30 ml blood sample (6 EDTA tubes) will be taken at inclusion in the study, in addition to the blood sample taken as part of the routine care.
This sampling is carried out for :
- Search for CHIP-associated mutations in circulating leukocytes
- Plasma determination of IL-1β, IL-6, IL-10 and TNF-α
| Study group | Role | What they receive |
|---|---|---|
| First CVE | Experimental | Not described Receives: Biological: Specific blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of a CHIP
Defined as the presence of a mutation (in the genes DNMT3A, TET2, ASXL1, SF3B1, TP53, CBL, SRSF2, GNB1 and PPM1D) (with an allelic frequency greater than 2, 5 or 10%).
Measured: Day 1
Secondary outcomes (4)
Frequency of CHIP
The frequency of CHIP in this cohort will be compared to the one observed in a control population (recruited from the 3-cities study cohort or 3C).
Measured: Day 1
Assessment of systemic inflammation
Assessed by the level of plasmatic CRP, IL-1β, IL-6, IL-10 and TNF-α.
Measured: Day 1
Assessment of Atherosclerosis level
Assessed by 3D ultrasound analysis. An innovative technique for monitoring the volume of carotid plaques.
Measured: Day 1
Presence of cardiovascular risk factor
Evaluated by the investigators.The cardiovascular risk factor are defined as :
- Active smoking or smoking cessation for less than 3 years
- HyperLDLemia (LDL Cholesterol > 3.36 mmol/L)
- HypoHDLemia (HDL < 1.03 mmol/L in men or < 1.29 mmol/L in women)
- Diabetes (2 blood glucose levels > 6.93 mmol/L)
- Hypertension (hypertension) (> 140/90 mmHg) treated or not.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start23 Jun 2020
- Primary completion3 Oct 2021
- Study completion3 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Thierry COUFFINHAL, MD-PhD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581057
- Sponsor's protocol ID
- CHUBX 2019/18
- Acronym
- CHATH
- Status last verified
- Feb 2022
- First submitted
- 2 Oct 2020
- Last updated
- 22 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fawaz S, Marti S, Dufossee M, Pucheu Y, Gaufroy A, Broitman J, Bidet A, Soumare A, Munsch G, Tzourio C, Debette S, Tregouet DA, James C, Mansier O, Couffinhal T. Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies. Elife. 2024 Dec 12;13:RP96150. doi: 10.7554/eLife.96150.
PubMed 39665621
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frequency of Clonal Hematopoiesis in Patients Over 75 With a First Cardio Vascular Event. Consequences on Inflammation and Atherosclerosis
- ClinicalTrials.gov ID
- NCT04581057
- Acronym / sponsor ID
- CHATH / CHUBX 2019/18
- Conditions
- Myocardial Infarction
- Keywords
- CHIP, Cardiovascular events, Atherosclerosis, Inflammation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 23 Jun 2020 (actual)
- Primary completion
- 3 Oct 2021 (actual)
- Study completion
- 3 Oct 2021 (actual)
- First posted
- 9 Oct 2020 (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.
This study aims at evaluating the prevalence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients over 75 presenting with a first cardio-vascular event (CVE). The investigators will also determine if CHIPs are more frequent in this population compared to a control cohort without CVE. An association between CHIP, a systemic inflammation and increased atherosclerosis will also be assessed.
Detailed description
Despite increasing knowledge on the pathophysiology of cardio-vascular diseases (in particular the role of inflammation in the development of atherosclerosis), predicting their occurrence remains largely difficult. Aging remains the most powerful factor for predicting the occurrence of myocardial infarction, independently from other identified risk factors. Few years ago, acquired mutations were described in the hematopoietic system of apparently healthy subjects. This phenomenon, now described as CHIP (Clonal Hematopoiesis of Indeterminate Potential) is more frequently observed in elderly people, and has been recently linked to an increased risk of cardio-vascular events. Experiments in mice demonstrated that these CHIPs are responsible for an inflammation that supports the development of atherosclerosis. However the link between CHIP, inflammation and atherosclerosis has never been demonstrated in humans.
In this study, the investigators will search for an increased frequency of CHIP in patients with a first cardio-vascular event (CVE). Seven months after the CVE, a blood sample will be taken. Mutations in the 9 most frequently mutated genes in CHIP will be evaluated by Next Generation Sequencing. Systemic inflammation will be evaluated by measurement of circulating levels of CRP, IL-1β, IL-6, IL-10 and TNF-α. Atherosclerosis will be evaluated via the volume of atherosclerotic plaques as assessed by 3D ultrasound analysis. The presence of CHIP will be correlated to traditional cardiovascular risk factors, systemic inflammation markers and the level of atherosclerosis. The investigators will also assess the relationship between the presence of CHIP and the risk of CVE reoccurrence.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| First CVE | Experimental | Biological: Specific blood sampling |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- Patients (male or female) over 75 years old
- Patients with a first CVE (myocardial infarction) of atheromatous origin that occurred between 2 and 7 months before inclusion
- Absence of evidence of hematological malignancy (known or obvious by the results of blood counts)
- Subject registered with a social security scheme
- Written informed consent obtained
Key exclusion criteria (16 listed)
- Patients who did not presented any CVE in the last 7 months
- Patients with CVE with a non-atheromatous origin (dissection, embolic, …)
- Presence of an unbalanced diabetes (defined as HbA1C > 10%)
- History of previous CVE before 75 year-old : myocardial infarction, stroke of atheromatous origin
- Hematological malignancy (known or obvious on the results of blood counts)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Specific blood samplingA 30 ml blood sample (6 EDTA tubes) will be taken at inclusion in the study, in addition to the blood sample taken as part of the routine care. This sampling is carried out for : * Search for CHIP-associated mutations in circulating leukocytes * Plasma determination of IL-1β, IL-6, IL-10 and TNF-α | Biological | First CVE |
Primary outcome
Presence of a CHIP
Time frame: Day 1
Defined as the presence of a mutation (in the genes DNMT3A, TET2, ASXL1, SF3B1, TP53, CBL, SRSF2, GNB1 and PPM1D) (with an allelic frequency greater than 2, 5 or 10%).
4 secondary outcomes
Frequency of CHIP
Time frame: Day 1
Assessment of systemic inflammation
Time frame: Day 1
Assessment of Atherosclerosis level
Time frame: Day 1
Presence of cardiovascular risk factor
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2022.
- Derived from this study: PubMed 39665621Fawaz S, Marti S, Dufossee M, Pucheu Y, Gaufroy A, Broitman J, Bidet A, Soumare A, Munsch G, Tzourio C, Debette S, Tregouet DA, James C, Mansier O, Couffinhal T. Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies. Elife. 2024 Dec 12;13:RP96150. doi: 10.7554/eLife.96150.
- Individual participant dataSharing planned: No
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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.
Thierry COUFFINHAL, MD-PhD principal investigator
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Specific blood sampling in people with Myocardial Infarction, run by University Hospital, Bordeaux 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 16 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: finished, as of the sponsor's last update on 22 Feb 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Presence of a CHIP (time frame: Day 1). 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 NCT04581057, which also lists 1 linked publication.
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 22 Feb 2022.