Heart Failure With Preserved Ejection FractionCHiEFNCT05828888
CHIP in Endothelial Dysfunction Associated With HEpEF
An observational study of Heart Failure With Preserved Ejection Fraction, run by University Hospital, Bordeaux.
Trial summary
This study aims at identifying processes that are deregulated in blood cells by Clonal Hematopoiesis of Indeterminate Potential (CHIP) which are involved in the development of heart failure with preserved ejection fraction (HEpEF). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2023to 1 Feb 2026
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 1. The cohort will be composed of 40 patients with HFpEF and 40 patients without. 2. Properties of peripheral leukocytes will be studied by scRNA-seq of * 3 patients with HFpEF and TET2 mutation * 3 patients with HFpEF and DNMT3A mutation * 2 patients with HFpEF but without CHIP * 3 patients with TET2 mutation but without HFpEF * 3 patients with DNMT3A mutation but without HFpEF * 2 patients without HFpEF nor CHIP
Who may be able to join
- HFpEF group and control group
- male or female
- 50 ≤ age ≤ 85 ans
- 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
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- HFpEF group
- patients with a diagnosis of HFpEF according to the criteria defined by the European society of cardiology
- Control group
- patients with a neuro-cardiovascular pathology without any link to coronaropathy nor heart failure
Who cannot join
- Hematological malignancy (known or obvious on the results of blood counts)
- Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases)
- Long term anti-inflammatory treatments:
- Corticoids
- Nonsteroidal anti-inflammatory drugs
- Aspirin (> 325 mg per day)
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- Cyclo-oxygenase II inhibitors
- Persons under judicial safeguards, trustee or curatorship
- 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
No sites are listed yet.
About this study
Official title: Role of Clonal Hematopoiesis of Indeterminate Potential in Endothelial Dysfunction Associated With Heart Failure With Preserved Ejection Fraction
This study aims at identifying processes that are deregulated in blood cells by Clonal Hematopoiesis of Indeterminate Potential (CHIP) which are involved in the development of heart failure with preserved ejection fraction (HEpEF).
Read the detailed description
Heart failure is responsible of 70,000 deaths every year in France. Heart failure can be divided into 2 categories depend on whether the ejection fraction is reduced (HFrEF) or preserved (HFpEF). Most of the treatments efficient in HFrEF are unable to prevent decompensating or reduce mortality associated with HFpEF. HFpEF pathophysiology remains poorly understood, which represents an obstacle to their management and to reduce cardiovascular events they are associated with.
Currently, it is admitted that cardiovascular risk factors (CVRF such as aging, female gender, diabetes mellitus, high blood pressure, hypercholesterolemia, obesity) are responsible of a low grade chronic inflammatory state that causes an endothelial dysfunction that contributes to the development of HFpEF.
However, not all patients with these CVRF develop HFpEF. Moreover, the mechanisms linking CVRF to inflammation or alteration of cardiomyocyte function by endothelial dysfunction remain unknown. This suggests that it exists a role for another factor that remains to be identified.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) result from the acquisition in hematopoietic stem cells of mutations associated with hematological malignancies, in the absence of any hematological disease. This situation initially described with a frequency of <5% before 60 years and >20% after 80 years old appears to be more frequent (>40% of people over 65 years). CHIP are mainly associated with the occurrence of cardiovascular events such as atherothrombosis and heart failure, possibly due to the induction of a chronic inflammation. Because CHIP are very frequent in the elderly and because CHIP are associated with inflammation and cardiovascular events, they could represent the missing link in the pathophysiology sequence that leads to the appearance of endothelial dysfunction and HFpEF development.
- Keywords
- Clonal Hematopoiesis of Indeterminate Potential (CHIP), Cardiovascular events, Heart Failure, Inflammation, Endothelial dysfunction
- Medical subject headings
- Heart Failure, Inflammation
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of clonal hematopoiesis indeterminate potential (CHIP)
Presence of CHIP defined as the presence of a mutation with an allele frequency greater than 2%.
Measured: Inclusion Visit
Secondary outcomes (2)
Diagnosis of heart failure with preserved ejection fraction
Diagnosis based on the European Society of Cardiology diagnostic sequence
Measured: Inclusion Visit
scRNA-seq analysis
Sixteen patients will be selected for scRNA-seq analysis:
- 3 patients with HFpEF and TET2 mutation
- 3 patients with HFpEF and DNMT3A mutation
- 2 patients with HFpEF but without CHIP
- 3 patients with TET2 mutation but without HFpEF
- 3 patients with DNMT3A mutation but without HFpEF
- 2 patients without HFpEF nor CHIP
Measured: 6 months (+/- 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2023
- Study start1 May 2023 (estimated)
- Primary completion1 May 2025 (estimated)
- Study completion1 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- INSERM - UMR 1219
- Responsible party
- Sponsor
- Investigators
- Olivier MANSIER, PharmD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05828888
- Sponsor's protocol ID
- CHUBX 2022/51
- Other IDs
- 2023-A00319-36
- Acronym
- CHiEF
- Status last verified
- Mar 2023
- First submitted
- 12 Apr 2023
- Last updated
- 25 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Clonal Hematopoiesis of Indeterminate Potential in Endothelial Dysfunction Associated With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT05828888
- Acronym / sponsor ID
- CHiEF / CHUBX 2022/51
- Keywords
- Clonal Hematopoiesis of Indeterminate Potential (CHIP), Cardiovascular events, Heart Failure, Inflammation, Endothelial dysfunction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- INSERM - UMR 1219
- Study start
- 1 May 2023 (estimated)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 Feb 2026 (estimated)
- First posted
- 25 Apr 2023 (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 identifying processes that are deregulated in blood cells by Clonal Hematopoiesis of Indeterminate Potential (CHIP) which are involved in the development of heart failure with preserved ejection fraction (HEpEF).
Detailed description
Heart failure is responsible of 70,000 deaths every year in France. Heart failure can be divided into 2 categories depend on whether the ejection fraction is reduced (HFrEF) or preserved (HFpEF). Most of the treatments efficient in HFrEF are unable to prevent decompensating or reduce mortality associated with HFpEF. HFpEF pathophysiology remains poorly understood, which represents an obstacle to their management and to reduce cardiovascular events they are associated with.
Currently, it is admitted that cardiovascular risk factors (CVRF such as aging, female gender, diabetes mellitus, high blood pressure, hypercholesterolemia, obesity) are responsible of a low grade chronic inflammatory state that causes an endothelial dysfunction that contributes to the development of HFpEF.
However, not all patients with these CVRF develop HFpEF. Moreover, the mechanisms linking CVRF to inflammation or alteration of cardiomyocyte function by endothelial dysfunction remain unknown. This suggests that it exists a role for another factor that remains to be identified.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) result from the acquisition in hematopoietic stem cells of mutations associated with hematological malignancies, in the absence of any hematological disease. This situation initially described with a frequency of <5% before 60 years and >20% after 80 years old appears to be more frequent (>40% of people over 65 years). CHIP are mainly associated with the occurrence of cardiovascular events such as atherothrombosis and heart failure, possibly due to the induction of a chronic inflammation. Because CHIP are very frequent in the elderly and because CHIP are associated with inflammation and cardiovascular events, they could represent the missing link in the pathophysiology sequence that leads to the appearance of endothelial dysfunction and HFpEF development.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 1. The cohort will be composed of 40 patients with HFpEF and 40 patients without. 2. Properties of peripheral leukocytes will be studied by scRNA-seq of * 3 patients with HFpEF and TET2 mutation * 3 patients with HFpEF and DNMT3A mutation * 2 patients with HFpEF but without CHIP * 3 patients with TET2 mutation but without HFpEF * 3 patients with DNMT3A mutation but without HFpEF * 2 patients without HFpEF nor CHIP
Key inclusion criteria (10 listed)
- HFpEF group and control group
- HFpEF group
- Control group
Key exclusion criteria (12 listed)
- Hematological malignancy (known or obvious on the results of blood counts)
- Chronic inflammatory disease (cancer, vasculitis, rheumatism, hepato-gastro-intestinal diseases)
- Long term anti-inflammatory treatments:
- Persons under judicial safeguards, trustee or curatorship
- Person deprived of judicial or administrative freedom
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
Presence of clonal hematopoiesis indeterminate potential (CHIP)
Time frame: Inclusion Visit
Presence of CHIP defined as the presence of a mutation with an allele frequency greater than 2%.
2 secondary outcomes
Diagnosis of heart failure with preserved ejection fraction
Time frame: Inclusion Visit
scRNA-seq analysis
Time frame: 6 months (+/- 3 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2023.
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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.
Olivier MANSIER, PharmD principal investigator
University Hospital, Bordeaux
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure With Preserved Ejection Fraction, run by University Hospital, Bordeaux.
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 10 inclusion and 12 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 25 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
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 Olivier MANSIER, PharmD,PhD (05 24 54 91 13 ext. +33, olivier.mansier@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of clonal hematopoiesis indeterminate potential (CHIP) (time frame: Inclusion Visit). 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 25 Apr 2023.