Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism

Healthy Clinical Trial

— COEURALDO  

Official title:

Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism Noninvasive Comparative Study in Humans of the Respective Cardiovascular Effects of Hyperaldosteronism and Hypertension by Magnetic Resonance Imaging

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02938910
• Other study ID #: P110912
• Status: Completed
• Phase: N/A
• First received: December 15, 2015
• Last updated: October 17, 2016
• Start date: November 2012
• Est. completion date: October 2014

Study information

• Verified date: October 2016
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministère de l'Enseignement supérieur et de la Recherche
• Study type: Observational

Clinical Trial Summary

Animal models have demonstrated the role of aldosterone in left ventricular remodeling involving fibrosis, apoptosis and hypertrophy. Myocardial fibrosis is a risk factor for serious arrhythmia and sudden death in ischemic and idiopathic hypertrophic heart disease. It is accepted that patients with primary aldosteronism have a higher prevalence of LV hypertrophy , arterial involvement and increased cardiovascular risk. In humans, a link has been demonstrated between aldosterone and heart failure as well as the benefit of the administration of an anti -aldosterone drug to lower mortality in this population , regardless of blood pressure level . The administration of spironolactone ( aldosterone ) in hypertensive rats has prevented the occurrence of aortic fibrosis . Plasma aldosteronism in humans has been associated with inflammation, fibrosis and aortic stiffness . However, primary aldosteronism is generally associated with so-called secondary hypertension . Chronic hypertension alone is a recognized etiological factor of myocardial hypertrophy ( myocardial fibrosis very advanced ) . The purpose of this study is to investigate the effects of MRI hyperaldosteronism on the heart.

Description:

Cross-sectional study with double analysis (A and B) with 2 x 2 sub-groups (ratio control/case 1/1)

• clinical situation: subjects are hypertensive. 20 subjects with primary aldosteronism will be compared to 20 patients with essential arterial hypertension

• clinical situation are normotensive subjects, 20 subjects with secondary aldosteronism loss in congenital salt (Bartter's syndrome / Gitelman) will be compared to 20 healthy volunteers. Controls (essential hypertension and healthy volunteers) are matched for age, sex and body size in two experimental groups (HAP and Gitelman). All subjects were recruited by the CIC of the European Georges Pompidou Hospital (Paris).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

• Patients with primary hyperaldosteronism:

• Aldosterone / renin plasma ratio SUP 64 pmol / mU

• aldosterone in a semi-sitting position SUP 500pmol / l or an aldosteronuria> 63nmol/24h,

• Both under neutral treatment for at least 15 days (alpha-blocker, calcium channel blockers, central inhibitors). BMI = 35 kg / m².

• For patients with secondary hyperaldosteronism :

• Documented diagnosis by the detection of mutation (s) homozygous or compound heterozygous for the gene SLC12A3 encoding CLCNKB chloride channel, or the gene encoding the HTSC Na-Cl cotransport thiazide sensitive.

• Normal blood pressure (mean of three consecutive measurements of SBP INF 140 mmHg and DBP INF 90 mmHg measured in a semi-sitting position after 5 minutes of rest).

• For hypertensive patients :

• Hypertension diagnosed on an average of three consecutive BP measurements = 140 and / or = 90 mmHg in the supine position after 5 minutes of rest or average daytime PA SUP 135/85 mmHg in ambulatory blood pressure monitoring (ABPM) in self-measurement , the presence of one or more antihypertensive medications regardless of the BP level.

• No argument for secondary hypertension (renal artery stenosis, hypermineralocorticoidism, pheochromocytoma, iatrogenic ...) or negative balance of secondary hypertension.

• BMI < 35 kg/m2.

• For healthy subjects :

• Normal blood pressure (mean of three consecutive measurements of SBP INF 140 mmHg and DBP INF 90 mmHg measured in a semi-sitting position after 5 minutes of rest).

• Absence of HA known or detected on determinations carried out during the study (see criteria for PAHs).

• BMI <35 kg / m²

• Laboratory tests (hematological and biochemical blood tests, urinalysis, serology and Research toxic) within normal limits or clinically acceptable for age and sex.

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Essential Hypertension
• Fibrosis
• Healthy
• Hyperaldosteronism
• Hypertension
• Primary Hyperaldosteronism
• Secondary Hyperaldosteronism

Intervention

Other:
• non interventional study
Non invasive imaging study without interventional procedures

Locations

Country	Name	City	State
France	Centre d\'investigation Clinique, hopital Europeen George Pompidou	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interstitial fibrosis assessed by MRI	Quantitative interstitial fibrosis indices (intra- and extra-cellular LV mass) derived from myocardial relaxation time T1 MRI will be estimated in 4 populations with and without hypertension (patients with essential hypertension or with primary hyperaldosteronism versus healthy volunteers or patients with Gitelman syndrome), and with and without high level of aldosterone (patients with primary hyperaldosteronism or Gitelman syndrome versus patients with essential hypertension or healthy volunteers)	One visit	No
Secondary	Evaluation of myocardial remodeling by MRI	Quantitative left ventricular remodeling (LV Mass and LV mass/end diastolic volume) will be estimated in 4 populations with and without hypertension (patients with essential hypertension or with primary hyperaldosteronism versus healthy volunteers or patients with Gitelman syndrome), and with and without high level of aldosterone (patients with primary hyperaldosteronism or Gitelman syndrome versus patients with essential hypertension or healthy volunteers)	One visit	No
Secondary	Effect of hypertension on myocardial fibrosis assessed by MRI	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of myocardial fibrosis	One visit	No
Secondary	Effect of aldosteronism on myocardial fibrosis assessed by MRI	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of myocardial fibrosis	One visit	No
Secondary	Effect of hypertension on LV diastolic dysfunction	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of LV diastolic dysfunction	One visit	No
Secondary	Effect of aldosteronism on LV diastolic dysfunction	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between the degree of LV diastolic dysfunction	One visit	No
Secondary	Effect of hypertension on the relationship between circulating biomarkers of fibrosis	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between circulating biomarkers of fibrosis	One visit	No
Secondary	Effect of aldosteronism on the relationship between circulating biomarkers of fibrosis	Analyze the relationship in each of the two clinical situations (HTA or absence of hypertension) between circulating biomarkers of fibrosis	One visit	No