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Assessment of the Relations Between Endothelial and Venous Dysfunctions and Left Ventricular Obstruction in Genetic Hypertrophic Cardiomyopathies (HCM-Vein)

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ClinicalTrials.gov Identifier: NCT04129905
Recruitment Status : Not yet recruiting
First Posted : October 17, 2019
Last Update Posted : October 17, 2019
Sponsor:
Collaborators:
Fédération Française de Cardiologie
Fondation Bordeaux Université
Amicus Therapeutics
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:

Left ventricular obstruction is an invalidating complication of hypertrophic cardiomyopathies (HCM), and endothelial dysfunction has also been observed in these pathologies. However, the relation between obstruction and endothelial and venous dysfunctions has not been previously studied.

The main objective is to investigate the relations between endothelial and venous dysfunctions and symptomatic left ventricular outflow-tract obstruction in HCM patients.


Condition or disease Intervention/treatment Phase
Hypertrophic Cardiomyopathy Endothelial Dysfunction Biological: BNP blood sample test Diagnostic Test: Electrocardiogram Diagnostic Test: Holter ECG Diagnostic Test: Echocardiography Diagnostic Test: Air venous plethysmography Diagnostic Test: Upper member arterial Doppler echography with analysis of FMD Biological: Endothelial function biomarkers Not Applicable

Detailed Description:

Hypertrophic cardiomyopathies (HCM) secondary to sarcomeric gene mutation or to Anderson-Fabry disease can be complicated by left ventricular (LV) outflow-tract obstruction responsible of disabling exercise symptoms. LV outflow-tract obstruction is a complex, multifactorial and dynamical phenomenon influenced by the degree of LV hypertrophy but also by mitral valve elongation and hemodynamical components including venous return (LV preload). The clinical and research team of Dr Réant, responsible of the Bordeaux Competence Center in hereditary or rare Cardiomyopathies, has recently demonstrated that LV outflow-tract obstruction can also be influenced by the conditions of realization of exercise echocardiography tests (position: upright versus supine, type: bicycle versus treadmill), and by an abnormal venous return capacity. In parallel, it has also been demonstrated, by other research teams, that HCM can be associated to endothelial and microvascular peripheral dysfunctions. However, to date, the relation between these two elements, and with sudden cardiac death risk, have not been previously studied.

The tests which will be performed during normal recommended follow-up of the HCM patients will be: Brain Natriuretic Peptide (BNP) blood sample test, electrocardiogram (ECG), Holter ECG, echocardiography at rest and during exercise.

The tests realized in addition will be:

  • air venous plethysmography: non invasive, and non painful test evaluating different parameters of venous filling by inflation of an armband around the leg, upright positioning, flexion-extension of the leg. Total duration estimated at 30-45 minutes.
  • upper member arterial Doppler echography with analysis of Flow Mediated Dilatation (FMD) : measurement of the evolution of brachial artery diameter before and after inflation of a armband during 5 minutes. Non invasive and non painful test, duration 30 minutes..
  • endothelial function biomarkers: blood sample test, 5 minutes. No follow-up is required for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Assessment of the Relations Between Endothelial and Venous Dysfunctions and Left Ventricular Obstruction in Genetic Hypertrophic Cardiomyopathies
Estimated Study Start Date : October 21, 2019
Estimated Primary Completion Date : October 21, 2020
Estimated Study Completion Date : October 21, 2020


Arm Intervention/treatment
Experimental: Symptomatic HCM patients
30 subjects (25-26 sarcomeric, 4-5 Fabry).
Biological: BNP blood sample test
Performed during normal recommended follow-up of the HCM patients.

Diagnostic Test: Electrocardiogram
Performed during normal recommended follow-up of the HCM patients.

Diagnostic Test: Holter ECG
Performed during normal recommended follow-up of the HCM patients.

Diagnostic Test: Echocardiography
Performed during normal recommended follow-up of the HCM patients. Echocardiography at rest and during exercise.

Diagnostic Test: Air venous plethysmography
Performed specifically for the research. Non invasive, and non painful test evaluating different parameters of venous filling by inflation of an armband around the leg, upright positioning, flexion-extension of the leg. Total duration estimated at 30-45 minute.

Diagnostic Test: Upper member arterial Doppler echography with analysis of FMD
Performed specifically for the research. Measurement of the evolution of brachial artery diameter before and after inflation of a armband during 5 minutes. Non invasive and non painful test, duration 30 minutes.

Biological: Endothelial function biomarkers
Performed specifically for the research. Blood sample test, 5 minutes.

Active Comparator: Healthy controls subjects
10 subjects (matched in age and sex to HCM patients) to obtain reference values of endothelial dysfunction.
Diagnostic Test: Air venous plethysmography
Performed specifically for the research. Non invasive, and non painful test evaluating different parameters of venous filling by inflation of an armband around the leg, upright positioning, flexion-extension of the leg. Total duration estimated at 30-45 minute.

Diagnostic Test: Upper member arterial Doppler echography with analysis of FMD
Performed specifically for the research. Measurement of the evolution of brachial artery diameter before and after inflation of a armband during 5 minutes. Non invasive and non painful test, duration 30 minutes.

Biological: Endothelial function biomarkers
Performed specifically for the research. Blood sample test, 5 minutes.




Primary Outcome Measures :
  1. Assessment of the venous ejection fraction [ Time Frame: Day 0 ]
    Via a plethysmography exam. The venous ejection fraction is measured in percentage.

  2. Assessment of the caliber variation of the brachial artery [ Time Frame: Day 0 ]
    Via a recording of arterial Doppler echography with analysis of FMD parameters. This parameter is measured in percentage.

  3. Measure of the Willebrand factor [ Time Frame: Day 0 ]

    The analysis of this biomarker of endothelial function is performed via a peripheral venous sample.

    This biomarker is measured in percentage.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients and volunteers:

    • Adults (age ≥18 years), male or female,
    • For female in age, efficient contraception will be required and a negative pregnancy test will be required,
    • Signed informed consent form will required for each included subject after having read the information note,
    • Affiliated to the national social security system,
  • Patients:

    .Patients diagnosed to have HCM secondary to sarcomeric mutation or to Fabry disease, symptomatic (dyspnea on exertion and/or chest pains during exercise),

  • Healthy volunteers:

    • Subjects without known cardiac disease,
    • No smokers.

Exclusion Criteria:

  • Patients and volunteers:

    • No cardiac pathology reducing life expectancy to less than 12 months (cancer),
    • Unbalanced arterial hypertension (systolic >160 mmHg and/or diastolic >120 mmHg),
    • Pregnancy or breastfeeding,
    • Major obesity > 140 kg,
    • Impossibility or refusal to give or sign the consent form,
    • Subject in period of exclusion relative to an other protocol,
    • Subject deprived of liberty by judicial or administrative decision,
    • Major protected by the Law
  • Patients:

    • Atrial fibrillation at the time of inclusion
    • Valvulopathy with severity greater than moderate.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04129905


Contacts
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Contact: Patricia REANT, MD (0)5 57 65 64 85 ext +33 patricia.reant@chu-bordeaux.fr
Contact: Christel DUPRAT (0)5 57 65 67 43 ext +33 christel.duprat@chu-bordeaux.fr

Locations
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France
University Hospital, Bordeaux
Pessac, France, 33604
Contact: Patricia REANT, MD    (0)5 57 65 64 85 ext +33    patricia.reant@chu-bordeaux.fr   
Contact: Christel DUPRAT    (0)5 57 65 67 43 ext +33    christel.duprat@chu-bordeaux.fr   
Sub-Investigator: Stéphane LAFFITE, MD-PhD         
Sub-Investigator: Amélie REYNAUD, MD         
Sub-Investigator: Matthieu MICHAUD, MD         
Sub-Investigator: Chloé JAMES, MD-PhD         
Sub-Investigator: Joël CONSTANS, MD-PhD         
Sub-Investigator: Didier LACOMBE, MD-PhD         
Sponsors and Collaborators
University Hospital, Bordeaux
Fédération Française de Cardiologie
Fondation Bordeaux Université
Amicus Therapeutics
Investigators
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Principal Investigator: Patricia REANT, MD University Hospital, Bordeaux
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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT04129905    
Other Study ID Numbers: CHUBX 2018/14
First Posted: October 17, 2019    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
Hypertrophic Cardiomyopathy
Endothelial Dysfunction
Venous return
Left ventricular outflow-tract obstruction
Sudden cardiac death risk
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases