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Protective Monocytes and Macrophages to Limit Decompensation and Heart Damaging (PROMOMA)

Primary Purpose

Left Ventricular Hypertrophy

Status
Not yet recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood sampling
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Left Ventricular Hypertrophy focused on measuring Left Ventricular Hypertrophy, Cardiac macrophages

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Pitié Salpêtrière Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Blood sampling

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 15, 2019
Last Updated
July 23, 2019
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Institute of Cardiometabolism and Nutrition, France
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1. Study Identification

Unique Protocol Identification Number
NCT04022330
Brief Title
Protective Monocytes and Macrophages to Limit Decompensation and Heart Damaging
Acronym
PROMOMA
Official Title
Protective Gr1low Monocytes and Macrophages in Compensated Cardiac Hypertrophy to Limit Decompensation and Heart Damaging
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 15, 2019 (Anticipated)
Primary Completion Date
April 15, 2023 (Anticipated)
Study Completion Date
April 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Institute of Cardiometabolism and Nutrition, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Left Ventricular Hypertrophy
Keywords
Left Ventricular Hypertrophy, Cardiac macrophages

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Blood sampling
Arm Type
Other
Intervention Type
Other
Intervention Name(s)
Blood sampling
Intervention Description
The blood sampling will be done just before surgery
Primary Outcome Measure Information:
Title
Identification of the complete spectrum of expressed mRNA of cardiac tissue macrophages.
Description
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).
Time Frame
18 months from start date
Secondary Outcome Measure Information:
Title
Identification of the complete transcriptome (including surface markers) of circulating monocytes from the blood collected for this project
Description
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.
Time Frame
24 months from start date
Title
Determination of the plasmatic factors in correlation with cardiac macrophage that may be specific for the compensated or decompensated state of left ventricular hypertrophy
Description
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.
Time Frame
24 months from start date
Title
mRNA of the circulating monocytes
Description
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.
Time Frame
24 months from start date

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reza TAVAKOLI, Dr
Phone
07 69 89 40 52
Email
r.tavakoli@ican-institute.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reza TAVAKOLI, Dr
Organizational Affiliation
Pitié Salpêtrière Hospital AP-HP
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pitié Salpêtrière Hospital
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reza TAVAKOLI, Dr
Phone
07 69 89 40 52
Email
r.tavakoli@ican-institute.org
First Name & Middle Initial & Last Name & Degree
Catherine PAVOINE, Dr
Phone
01 40 77 96 62
Email
catherine.pavoine@inserm.fr

12. IPD Sharing Statement

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Protective Monocytes and Macrophages to Limit Decompensation and Heart Damaging

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