Clinical trial NCT02430805: Predisposition and Transition Mechanisms From Arterial Hypertension to Heart Failure
Official title: Genetics and Genomics of Hypertension Associated With Microinflammation, Oxydative Stress, Chronic Renal Disease and Heart Failure (A2-B2-B3)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: hypertension
microinflammation and oxidative stress
renal disease
heart failure
genetics markers
genomics markers
proteomics markers
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: Network of Excellence 6 PCRD
First posted: 2015-04-30
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: This project aims at investigating the genetic, genomic and proteomic basis of hypertension and susceptibility to hypertension-related end organ damage (renal damage and heart failure). It will include cross sectional as well as follow-up studies with a large number of subjects and variety of phenotypes, to explore the pathophysiology of hypertension and hypertension-related disease.

Detailed description: In all index patients and recruited family members, recorded data will include the following :

* Past medical history, drug history and family history
* Physical examination
* Height, weight, waist and hip circumference
* Cardiac examination
* Vascular examination
* Blood pressure
* Plasma and urine samples
* Body composition (DEXA)
* Tissue Doppler imaging

Eligibility criteria: Inclusion Criteria:

* index patient :

  * Caucasian patients of either sex who were diagnosed to have essential hypertension (as defined below) before the age of 50 y.
  * The index patient should not be older than 60 years at the time of enrolment.
  * Definition of hypertension for the index patient:

    * If untreated: Systolic blood pressure \> 160 mmHg and/or diastolic blood pressure \> 95 mmHg.
    * If already on treatment: Treatment with more of 2 different antihypertensive drugs at the time of enrolment.
  * At least three first degree relatives of whom at least one should be affected and at least one be from a different generation (parents or offspring aged 18 years or above) must be willing to participate in the family study. For definition of hypertension in relatives of the index patient see below.
  * Written informed consent
* family

  * at least three other first degree relatives must be willing to participate in the family study:
  * at least one first-degree relative must be affected with diagnosis of hypertension made before age of 50 years AND
  * at least one first degree relative must be from a different generation (offspring or parents).

Exclusion Criteria:

* index patient :

  * Any known form of secondary hypertension, including sleep apnoea syndrome
  * Any known previous clinical complications of hypertension (angina, MI, stroke, TIA, peripheral artery disease) at any time
  * Any known renal disease, including GFR \< 60 mL/min as estimated by the abbreviated MDRD formula, or kidney stones
  * Kidney or other organ transplantation
  * Type 1 diabetes mellitus
  * Heart failure stage D (AHA/ACC criteria)
  * Any malignant concomitant diseases or history of malignant diseases within the last five years, with exception of treated squamous skin cancer or basalioma
  * Clinical or laboratory signs of acute infection, especially urinary tract infection
  * Systemic inflammatory diseases, such as autoimmune diseases, connective tissue diseases or collagenoses.
  * Steroids or any other immunosuppressive drug
  * Severe known liver disease (ALT or gamma-GT above three-fold of upper normal limit)
  * Current alcohol consume of more than 21 drinks/week (1 drink = a bottle (0,33 l) beer, a glass (0,2 l) of wine, or 4 cl = 40 ml of spirit (40%)) or drug abuse such as cocaine
* family

  * any organ transplantation
  * any malignant concomitant disease
  * acute infection
  * systemic inflammatory disease
  * severe liver disease
  * current alcohol or drug abuse

Primary outcomes:
measure: genetic biomarkers
timeFrame: time point 1 : first day ; Time point
Secondary outcomes:
measure: oxidative stress markers
timeFrame: time point 1 : first day ; Time point 2 : 2 years ; Time point 3 : 4 years
measure: microinflammation markers
timeFrame: time point 1 : first day ; Time point 2 : 2 years ; Time point 3 : 4 years
measure: renal function and damage markers
timeFrame: time point 1 : first day ; Time point 2 : 2 years ; Time point 3 : 4 years
measure: cardiac and large artery growth, remodelling dysfunction and failure markers
timeFrame: time point 1 : first day ; Time point 2 : 2 years ; Time point 3 : 4 years
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Centre D'Investigation Clinique de Strasbourg
state: Alsace
city: Nancy
country: France
facility: Hopital Brabois adulte
state: Lorraine
Study officials:
affiliation: Central Hospital, Nancy, France
name: faiez ZANNAD, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mandry D, Girerd N, Lamiral Z, Huttin O, Filippetti L, Micard E, Beaumont M, Ncho Mottoh MB, Pace N, Zannad F, Rossignol P, Marie PY. Relationship Between Left Ventricular Ejection Fraction Variation and Systemic Vascular Resistance: A Prospective Cardiovascular Magnetic Resonance Study. Front Cardiovasc Med. 2021 Dec 24;8:803567. doi: 10.3389/fcvm.2021.803567. eCollection 2021.