Clinical Trial: Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter

Brief Summary: Gitelman syndrome is a salt wasting tubulopathy caused by mutations in the SLC12A3 gene coding for the thiazide sensitive sodium chloride cotransporter. This disease mimics the chronic treatment with thiazide diuretics and is characterized by renal hypokalemia, low to normal blood pressure, hypocalciuria and hypomagnesemia. The purpose of this study is to determine whether the heterozygous carriers present the metabolic risks and/or the benefits of this disease.

Detailed Summary: Gitelman syndrome (GS), is an autosomal recessive salt wasting tubulopathy caused mainly by loss of function mutations in the SLC12A3 gene coding for the thiazide sensitive sodium-chloride cotransporter (NCC). Thus, GS mimics a chronic treatment with high doses of thiazide diuretics. NCC is expressed in the distal convoluted tubule, which is responsible for 7% of NaCl reabsorption. GS is the more frequent hereditary tubulopathie with estimated prevalence of 1/40000, which implicates that 1% of general population are heterozygous carriers (600 000 in France). Previous publications suggest that the apparently asymptomatic heterozygous carriers could present some clinical traits of GS or chronic thiazide treatment. These including: beneficial aspects (low blood pressure, low urinary calcium excretions) or metabolic risks (hypokalemia, insulin resistance). Nevertheless, these studies do not evaluate all the aspects and blood pressure was evaluated once in hospital setting. This study aims to compare home monitoring blood pressure; salt balance; potassium, glucose lipid and mineral metabolism and vascular function in 80 heterozygous carriers, 80 GS patients and 80 controls persons (without mutations in SLC12A3 gene).
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Systolic blood pressure evaluated by self-measurement [ Time Frame: 3 days ]

self-measurement at home, 3 times a day during 3 consecutive days


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Salt balance [ Time Frame: 1 day ]
    Blood renin and aldosterone measurements, 24h urinary sodium and aldosterone excretion
  • Potassium metabolism [ Time Frame: 1 day ]
    Dietary intake, blood potassium and 24 h urinary potassium excretion
  • Glucose and lipide metabolism [ Time Frame: 1 day ]
    BMI, blood glucose, insulin, cholesterol, LDL, HDL and triglycerides.
  • Oral glucose tolerance test [ Time Frame: 1 day ]
  • Mineral metabolism [ Time Frame: 1 day ]
    Blood and urinary calcium, magnesium and phosphate. bone remodeling markers
  • Renal fonction [ Time Frame: 1 day ]
    Estimated GFR, proteinuria and albuminuria
  • Vascular fonction evaluation [ Time Frame: 1 day ]
    Pulse wave analysis and central blood pressure. Blood and urinary vascular fonction markers


Original Secondary Outcome:

  • Salt balance [ Time Frame: 1 day ]
    Blood renin and aldosterone measurements, 24h urinary sodium and aldosterone excretion
  • Potassium metabolism [ Time Frame: 1 day ]
    Dietary intake, blood potassium and 24 h urinary potassium excretion
  • Lipide metabolism [ Time Frame: 1 day ]
    BMI, blood cholesterol, LDL, HDL and triglycerides.
  • Glucose, insulin, HOMA index, pre and post test [ Time Frame: 1 day ]
  • Mineral metabolism [ Time Frame: 1 day ]
    Blood and urinary calcium, magnesium and phosphate. PTH, 25 OH vitamin D calcitriol, bone remodeling markers
  • Renal function [ Time Frame: 1 day ]
    Estimated GFR, proteinuria and albuminuria
  • Vascular function evaluation [ Time Frame: 1 day ]
    Pulse wave velocity and central blood pressure. Blood and urinary vascular function markers


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: December 18, 2013
Date Started: December 2013
Date Completion:
Last Updated: January 13, 2017
Last Verified: January 2017