Search of Biomarkers of Mineralocorticoid Receiver Activity : the Value of Neutrophil Gelatinase Associated Lipocalin (NGAL)in Serum or Urine in Human

Cardiovascular Diseases Clinical Trial

Official title:

Prospective Study of Neutrophil Gelatinase Associated Lipocalin (NGAL)as a Biomarker of Mineralocorticoid Receiver Activity in Human: Proof of Concept.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02129621
• Other study ID #: 2007-A01008-45
• Status: Completed
• Phase: N/A
• First received: April 30, 2014
• Last updated: May 1, 2014
• Start date: May 2010
• Est. completion date: November 2012

Study information

• Verified date: January 2013
• Source: Central Hospital, Nancy, France
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Direction Générale de la Santé (DGS)
• Study type: Interventional

Clinical Trial Summary

Aldosterone and its target the mineralocorticoid receptor are implied in development of cardiovascular disease such as arterial high blood pressure or cardiac failure. Serum aldosterone level is insufficient to know if the mineralocorticoid receptor is activated or not. The aim of this study is to identify biomarkers of mineralocorticoid receptor activity. The first "candidate biomarker" is Neutrophil gelatinase-associated lipocalin (NGAL) or "lipocalin" which being measured in blood or in the urine. According to scientific knowledge's evolution, others biomarkers could be tested later thanks to the blood or urinary samples taken during study.

Description:

This study is broken up into 5 groups:

The first is a pre-analytical study to determinate optimum conditions for lipocalin samples.

The second focuses on intra-individual variations of lipocalin levels in blood and urine.

The third determinate the normal values of lipocalin in blood and urine. Fourthly, we study the role of renal function on serum and urines lipocalin levels.

Fifthly, we study the role of anti-aldosterone treatment on patients who suffer of primary hyperaldosteronism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

For the group 1 and 2

Inclusion criteria:

• Men having an age ranging between 18 and 35 years

• Unhurt subject of any acute pathology for more than 7 days

• Consent signed by the subject

Exclusion criteria:

• Subject presenting a known arterial high blood pressure (blood pressure > 140/90 mmHg) or any cardiovascular history

• Subject presenting a known renal insufficiency

• Subject presenting a known anaemia (Hb < 12g/dl)

• Subject presenting a known diabetes

• Subject presenting a cancer diagnosed less than 5 years previously or evolutionary cancer

• Subject presenting a chronic liver disease

• Subject presenting a connectivite: Rhumatoid polyarthritis....

• Crohns disease

• Current tuberculosis

• Any medicinal treatment

• Subject participating in another protocol or in exclusion's period for another protocol

• Absence of social insurance

For group 3

Inclusion criteria:

• Men or women having an age ranging between 18 and 85 years

• Unhurt subject of any acute pathology for more than 7 days

• without any cardiovascular treatment

• Consent signed by the subject

Exclusion criteria:

• Subject presenting a known arterial high blood pressure (blood pressure > 140/90 mmHg or > 160/95 mmHg after 60 years)

• Subject presenting a known renal insufficiency

• Subject presenting a known diabetes

• Woman who is pregnant

• Subject presenting a cancer diagnosed less than 5 years previously or evolutionary cancer

• Subject presenting a chronic liver disease

• Subject presenting a connectivite: Rhumatoid polyarthritis....

• Crohns disease

• Current tuberculosis

• Subject presenting an effort angor or other coronaropathy

• Subject with antecedant of endarterectomy of carotid

• Subject with known abdominal aorta aneurism

• Subject participating in another protocol or in exclusion's period for another protocol

• Absence of social insurance

For group 4

Inclusion criteria:

• Men or women having an age ranging between 18 and 85 years

• Subject with chronique renal insufficiency

• Consent signed by the subject

Exclusion criteria:

• Subject presenting a known diabetes

• Woman who is pregnant

• Subject presenting a cancer diagnosed less than 5 years previously or evolutionary cancer

• Subject presenting a chronic liver disease

• Subject presenting a connectivite: Rhumatoid polyarthritis....

• Crohns disease

• Current tuberculosis

• Subject presenting an effort angor or other coronaropathy

• Subject with antecedant of endarterectomy of carotid

• Subject with known abdominal aorta aneurism

• Subject participating in another protocol or in exclusion's period for another protocol

• Absence of social insurance

For the group 5

Inclusion Criteria:

• Men or women having an age ranging between 30 and 60 years

• Hypertensive subject suffering from primary hyperaldosteronism defined by an aldosteron/renin ratio > 64 pmol/mL in position lying and an aldosteron level > 500pmol lying down (or > 550pmol/L seated or standing) or urinary aldosteron level > 63 nmol/24 hours; for whom

• Subjects having an indication for a monotherapy treatment by ALDACTONE (1 or 2 mg/kg/j)during preoperative period, possibly associated if need be with a calcic inhibitive treatment, central or alphabloquant treatment.

• Subject without other cardiovascular history (myocardic infarction, decompensation of cardiac insufficiency, intellectual vascular accident) and with a normal renal function according to the age,the sex and the blood value of creatinine by the formula MDRD (Flow of renal filtration > 60mL/min/1,73)

• Consent signed by the subject

Exclusion Criteria:

• Subject presenting others forms of high blood pressure (consumption of products or medicines which can facilitate or deteriorate the high blood pressure (alcohol, licorise (of whom the "pastis" without alcohol), anti-inflammatory drugs, corticosteroids, ciclosporin, erythropoiétin, cocain), hyperthyroidy, hypercorticism, chronic renal disease: urinary protein level < 0.3 g/l and clearance of the creatinine > 60ml/min/1.73m2), arterial renal stenosis

• Counter -indication of realization of a test of salt injection

• Current pregnancy

• Subject presenting a cancer diagnosed less than 5 years previously or evolutionary cancer

• Chronic liver disease

• Subject presenting a connectivite: Rheumatoid polyarthritis....

• Crohns disease

• Current tuberculosis

• Absence of social insurance

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Procedure:
• Urinary and blood lipococalin levels determination
Blood test on an empty stomach. Urinary taking on arrival in the service

Drug:
• Spironolactone
For the group 5, at the time of the V0 visit, a treatment by aldactone will be set up (posology: 1 to 2 mg/kg).

Locations

Country	Name	City	State
France	Brabois Hospital	Nancy
France	Georges Pompidou Hospital	Paris
France	Unit of arterial high blood pressure of the Georges Pompidou Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lipocalin blood and urinary concentrations	Serum and urinary lipocalin concentrations will be evaluated using comercially available kits (Kits lipocalin-2/NGAL (NCAL20))	8 months	No