Genetic Determinant of Blood Pressure Sensitivity to Salt Intake (JEU004)

Clinical, Pharmacological and Biological Investigations of a Polymorphism of Nedd4 , a Regulatory Protein of the Epithelial Sodium Channel

Nedd4.2 is a regulator of ENac, a transporter of sodium involved in the regulation of salt retention by the kidney. The study address the consequence of a frequent genetic variation leading expected to impact the function of Nedd4 and in turn, the ability of kidneys to excrete salt intake. Our hypothesis is that the genetic variants of Nedd4.2 could constitute a genetic predisposition to (or protection against) salt-sensitive hypertension.

Study Overview

• Status: Terminated
• Conditions: Hypertension
• Intervention / Treatment: Other: Diet Amiloride

Detailed Description

Subjects were submitted one week to a low sodium-high potassium diet, and then switch to a high sodium,-low potassium diet for two weeks. the last week, subject were taken a 20 MG daily dose of amiloride, a potassium sparing diuretic.

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy volunteers
• between 18 and 35 years odl
• BMI between 18 and 28 Kg per m2
• non smokers
• no active disease
• no alcool or drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet Amiloride; One week Low Na diet (10 mmol/d) followed by ine week high Na diet (200 mmol/d) followed by 2 weeks administration of amiloride (10 mg the 1 st week and the 20mg).	Other: Diet Amiloride; only arm of the trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Blood Pressure among genotypes	24h AMBP will be measured weekly for the duration of study, an expected average of 3 weeks	24h AMBP will be measured weekly for the duration of study, an expected average of 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ambulatory Blood Pressure (AMBP)	24h AMBP was measured fourth : at the beginning of the study,at the end of the low sodium-high potassium diet, after one week under the high sodium-low potassium diet and at the end of amiloride treatment under high sodium-low potassium diet	three weeks

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Xavier Jeunemaître, PD, PhD, genetic department

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Estimate): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 12, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: blood pressure; polymorphism; salt intake; Nedd4-2; between 18 and 35 years old; BMI between 18 and 28 Kg per m2; no active disease; no alcool or drug abuse or smoke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing; Acid Sensing Ion Channel Blockers; Epithelial Sodium Channel Blockers; Amiloride
• Other Study ID Numbers: P060215