Left Ventricular HypertrophyPROMOMANCT04022330
Protective Monocytes and Macrophages to Limit Decompensation and Heart Damaging
A study testing Blood sampling in people with Left Ventricular Hypertrophy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The working hypothesis is that cardiac macrophages specific for the compensated cardiac hypertrophic phase limit the progression toward the decompensated state of heart failure by promoting an inflammatory environment favouring cardiomyocyte survival and preservation of the pump function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Left Ventricular Hypertrophy
- What is being tested?
- Blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteFrance
- Study dates
- 15 Oct 2019to 15 Apr 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Older than 18 years
- Patients affiliated to a social security regimen
- Informed signed consent
- Group 1 : compensated
- Symptomatic patients with severe aortic valve stenosis associated with asymmetric septal hypertrophy or patients with hypertrophic obstructive cardiomyopathy (HOCM), with echocardiographic transvalvular gradient ≥ 40 mmHg associated with echocardiographic septal/posterior wall thickness ≥ 1.3 ejection fraction ≥ 50%, planned for aortic valve replacement with septal myomectomy or septal myomectomy for HOCM
- Group 2 : transition • Symptomatic patients with severe aortic valve stenosis associated with asymmetric septal hypertrophy or patients with hypertrophic obstructive cardiomyopathy (HOCM), with echocardiographic transvalvular gradient ≥ 40 mmHg associated with echocardiographic septal/posterior wall thickness ≥ 1.3 ejection fraction < 50%, planned for aortic valve replacement with septal myomectomy or septal myomectomy for HOCM
- Group 3 : decompensated
- End-stage heart failure on the waiting list for cardiac transplantation or undergoing ventricular assist device implantation as a bridge to transplantation
Who cannot join
- Combined aortic valve replacement and coronary artery bypass grafting or mitral/tricuspid surgery
- Emergency operation
- Acute endocarditis
- Patient unable to give his consent
- Patient deprived of freedom or under legal protection (guardianship or curatorship)
- Pregnant or breastfeeding woman
Trial locations and contacts
1 site in 1 country.
France1 site
Pitié Salpêtrière Hospital
Paris, 75013
Reza TAVAKOLI, Dr, 07 69 89 40 52, r.tavakoli@ican-institute.org
Catherine PAVOINE, Dr, 01 40 77 96 62, catherine.pavoine@inserm.fr
About this study
Official title: Protective Gr1low Monocytes and Macrophages in Compensated Cardiac Hypertrophy to Limit Decompensation and Heart Damaging
The working hypothesis is that cardiac macrophages specific for the compensated cardiac hypertrophic phase limit the progression toward the decompensated state of heart failure by promoting an inflammatory environment favouring cardiomyocyte survival and preservation of the pump function. The investigators will perform studies in human plasma and monos, cardiac tissues and macrophages to validate this hypothesis.
Read the detailed description
Left ventricular hypertrophy (LVH) occurs following acute and chronic phases of ischemic heart disease as well as during pressure and/or volume overload (arterial hypertension, valvular heart disease). Persistence of the pathological stimuli, i.e. pressure and/or volume overload, will ultimately lead to the decompensation of cardiac function described as heart failure (HF). HF is worldwide one of the major healthcare concerns both in terms of the loss of human life and economic burden due to the expanding costs of care for patients with this condition (Ambrosy 2014). HF is associated with cardiomyocyte death, exacerbated inflammatory reaction with ensuing fibrosis and alteration of local angiogenesis. A better understanding of the mechanisms involved in the maintenance of the compensated state and in the transition to heart failure will promote the conception of new pharmacological interventions to prevent or even to reverse the transition to heart failure. Based on preclinical studies, the aim of this study is to advance our knowledge of relevant mechanisms involved in this process.
In an experimental setting in mice, the protective role of macrophages presenting an anti-inflammatory polarization in the progression of isuprel-induced left ventricular hypertrophy to irreversible heart failure has been recently demonstrated (Keck et al., submitted). These findings in the experimental model encourage their confirmation in the clinical setting. In the latter case, new therapeutic strategies can be projected to prevent or even to reverse the transition of compensated cardiac hypertrophy to heart failure.
To this purpose, the investigators will study cardiac tissue and blood sample of patients presenting compensated cardiac hypertrophy compared to those with end-stage heart failure.
Patients undergoing aortic valve replacement associated with septal myomectomy for aortic valve stenosis and asymmetric septal hypertrophy as well as patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myomectomy are included in the group of compensated cardiac hypertrophy. Patients undergoing heart transplantation or implantation of mechanical life supporting system are included in the group of end-stage heart failure.
- Conditions
- Left Ventricular Hypertrophy
- Being tested
- Blood sampling
- Keywords
- Left Ventricular Hypertrophy, Cardiac macrophages
- Medical subject headings
- Hypertrophy, Left Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samplingOther
The blood sampling will be done just before surgery
| Study group | Role | What they receive |
|---|---|---|
| Blood sampling | Other | Not described Receives: Other: Blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of the complete spectrum of expressed mRNA of cardiac tissue macrophages.
This complete mRNA profile obtained in patients will be compared to the one found in preclinical studies in mice. The genes that are expressed during compensated cardiac hypertrophy in both human and mouse will be sorted out. The expression of the latter genes will be correlated to the cardiac pump function in order to select in the macrophage transcriptome potential markers of compensated cardiac hypertrophy. The presence of these specific macrophage markers will be investigated on frozen cardiac tissue sections by immune-histochemistry and by real time polymerase chain reaction (rtPCR).
Measured: 18 months from start date
Secondary outcomes (3)
Identification of the complete transcriptome (including surface markers) of circulating monocytes from the blood collected for this project
The transcriptome of circulating monocytes will be identified by mRNA sequencing. This complete mRNA profile obtained in patients will be compared to the one found in preclinical studies in mice and the genes that are expressed during compensated cardiac hypertrophy in both human and mouse will be sorted out. The expression of the latter genes will be correlated to the cardiac pump function in order to select in the circulating monocyte transcriptome potential markers of compensated cardiac hypertrophy. The presence of these specific circulating monocyte markers will be investigated by rtPCR.
Measured: 24 months from start date
Determination of the plasmatic factors in correlation with cardiac macrophage that may be specific for the compensated or decompensated state of left ventricular hypertrophy
Assessment of the presence of plasmatic factors: Based on preclinical studies showing circulating plasmatic markers of the compensated cardiac hypertrophic state, the same biomarkers will be assessed in plasma of the patients by ELISA. The concentration of these plasmatic factors will be correlated to the cardiac pump function in order to select potential markers of compensated cardiac hypertrophy.
Measured: 24 months from start date
mRNA of the circulating monocytes
Characterization of mRNA of the circulating monocytes that in correlation with those of cardiac tissue macrophages may be specific for the compensated or decompensated state of left ventricular hypertrophy and thus protective against transition to heart failure.
Measured: 24 months from start date
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2019
- Study start15 Oct 2019 (estimated)
- Primary completion15 Apr 2023 (estimated)
- Study completion15 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Left Ventricular HypertrophyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France
- Responsible party
- Sponsor
- Investigators
- Reza TAVAKOLI, Dr, Principal investigator, Pitié-Salpêtrière Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04022330
- Sponsor's protocol ID
- APHP190224
- Other IDs
- 2019-A000751-56
- Acronym
- PROMOMA
- Status last verified
- Jul 2019
- First submitted
- 15 Jul 2019
- Last updated
- 25 Jul 2019
- 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 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protective Gr1low Monocytes and Macrophages in Compensated Cardiac Hypertrophy to Limit Decompensation and Heart Damaging
- ClinicalTrials.gov ID
- NCT04022330
- Acronym / sponsor ID
- PROMOMA / APHP190224
- Conditions
- Left Ventricular Hypertrophy
- Keywords
- Left Ventricular Hypertrophy, Cardiac macrophages
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institute of Cardiometabolism and Nutrition, France
- Study start
- 15 Oct 2019 (estimated)
- Primary completion
- 15 Apr 2023 (estimated)
- Study completion
- 15 Apr 2024 (estimated)
- First posted
- 17 Jul 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 working hypothesis is that cardiac macrophages specific for the compensated cardiac hypertrophic phase limit the progression toward the decompensated state of heart failure by promoting an inflammatory environment favouring cardiomyocyte survival and preservation of the pump function. The investigators will perform studies in human plasma and monos, cardiac tissues and macrophages to validate this hypothesis.
Detailed description
Left ventricular hypertrophy (LVH) occurs following acute and chronic phases of ischemic heart disease as well as during pressure and/or volume overload (arterial hypertension, valvular heart disease). Persistence of the pathological stimuli, i.e. pressure and/or volume overload, will ultimately lead to the decompensation of cardiac function described as heart failure (HF). HF is worldwide one of the major healthcare concerns both in terms of the loss of human life and economic burden due to the expanding costs of care for patients with this condition (Ambrosy 2014). HF is associated with cardiomyocyte death, exacerbated inflammatory reaction with ensuing fibrosis and alteration of local angiogenesis. A better understanding of the mechanisms involved in the maintenance of the compensated state and in the transition to heart failure will promote the conception of new pharmacological interventions to prevent or even to reverse the transition to heart failure. Based on preclinical studies, the aim of this study is to advance our knowledge of relevant mechanisms involved in this process.
In an experimental setting in mice, the protective role of macrophages presenting an anti-inflammatory polarization in the progression of isuprel-induced left ventricular hypertrophy to irreversible heart failure has been recently demonstrated (Keck et al., submitted). These findings in the experimental model encourage their confirmation in the clinical setting. In the latter case, new therapeutic strategies can be projected to prevent or even to reverse the transition of compensated cardiac hypertrophy to heart failure.
To this purpose, the investigators will study cardiac tissue and blood sample of patients presenting compensated cardiac hypertrophy compared to those with end-stage heart failure.
Patients undergoing aortic valve replacement associated with septal myomectomy for aortic valve stenosis and asymmetric septal hypertrophy as well as patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing septal myomectomy are included in the group of compensated cardiac hypertrophy. Patients undergoing heart transplantation or implantation of mechanical life supporting system are included in the group of end-stage heart failure.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood sampling | Other | Other: Blood sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Older than 18 years
- Patients affiliated to a social security regimen
- Informed signed consent
- Group 1 : compensated
- Symptomatic patients with severe aortic valve stenosis associated with asymmetric septal hypertrophy or patients with hypertrophic obstructive cardiomyopathy (HOCM), with echocardiographic transvalvular gradient ≥ 40 mmHg associated with echocardiographic septal/posterior wall thickness ≥ 1.3 ejection fraction ≥ 50%, planned for aortic valve replacement with septal myomectomy or septal myomectomy for HOCM
Key exclusion criteria (6 listed)
- Combined aortic valve replacement and coronary artery bypass grafting or mitral/tricuspid surgery
- Emergency operation
- Acute endocarditis
- Patient unable to give his consent
- Patient deprived of freedom or under legal protection (guardianship or curatorship)
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 |
|---|---|---|
| Blood samplingThe blood sampling will be done just before surgery | Other | Blood sampling |
Primary outcome
Identification of the complete spectrum of expressed mRNA of cardiac tissue macrophages.
Time frame: 18 months from start date
This complete mRNA profile obtained in patients will be compared to the one found in preclinical studies in mice. The genes that are expressed during compensated cardiac hypertrophy in both human and mouse will be sorted out. The expression of the latter genes will be correlated to the cardiac pump function in order to select in the macrophage transcriptome potential markers of compensated cardiac hypertrophy. The presence of these specific macrophage markers will be investigated on frozen cardiac tissue sections by immune-histochemistry and by real time polymerase chain reaction (rtPCR).
3 secondary outcomes
Identification of the complete transcriptome (including surface markers) of circulating monocytes from the blood collected for this project
Time frame: 24 months from start date
Determination of the plasmatic factors in correlation with cardiac macrophage that may be specific for the compensated or decompensated state of left ventricular hypertrophy
Time frame: 24 months from start date
mRNA of the circulating monocytes
Time frame: 24 months from start date
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2019.
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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.
Reza TAVAKOLI, Dr principal investigator
Pitié-Salpêtrière Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sampling in people with Left Ventricular Hypertrophy, run by Assistance Publique - Hôpitaux de Paris 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 8 inclusion and 6 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 Jul 2019. 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?
Contact Reza TAVAKOLI, Dr (07 69 89 40 52, r.tavakoli@ican-institute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of the complete spectrum of expressed mRNA of cardiac tissue macrophages. (time frame: 18 months from start date). 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 Jul 2019.