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Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter (HEPHYGI)

Primary Purpose

Heterozygous Carriers of Gitelman Syndrome

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Samplings of blood
Sampling of urine
Measure of the blood pressure
glycemia test
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Heterozygous Carriers of Gitelman Syndrome focused on measuring Gitelman, Heterozygous SLC12A3 mutation, Blood pressure, Hypokalemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers
Gitelman syndrome patients, relatives carrying heterozygous mutations and relatives or healthy voluntarees without mutations.

Sites / Locations

  • Nephrology Department. Centre Hospitalier Universitaire, Hôpital Dupuytren
  • Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot.
  • Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon
  • Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou.
  • Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil.

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

study's population

Arm Description

Outcomes

Primary Outcome Measures

Systolic blood pressure evaluated by self-measurement
self-measurement at home, 3 times a day during 3 consecutive days

Secondary Outcome Measures

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

Full Information

First Posted
December 18, 2013
Last Updated
January 13, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT02035046
Brief Title
Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter
Acronym
HEPHYGI
Official Title
Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France

4. Oversight

Data Monitoring Committee
No

5. Study Description

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 Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heterozygous Carriers of Gitelman Syndrome
Keywords
Gitelman, Heterozygous SLC12A3 mutation, Blood pressure, Hypokalemia

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
250 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
study's population
Arm Type
Other
Intervention Type
Procedure
Intervention Name(s)
Samplings of blood
Intervention Type
Procedure
Intervention Name(s)
Sampling of urine
Intervention Type
Procedure
Intervention Name(s)
Measure of the blood pressure
Intervention Type
Procedure
Intervention Name(s)
glycemia test
Primary Outcome Measure Information:
Title
Systolic blood pressure evaluated by self-measurement
Description
self-measurement at home, 3 times a day during 3 consecutive days
Time Frame
3 days
Secondary Outcome Measure Information:
Title
Salt balance
Description
Blood renin and aldosterone measurements, 24h urinary sodium and aldosterone excretion
Time Frame
1 day
Title
Potassium metabolism
Description
Dietary intake, blood potassium and 24 h urinary potassium excretion
Time Frame
1 day
Title
Glucose and lipide metabolism
Description
BMI, blood glucose, insulin, cholesterol, LDL, HDL and triglycerides.
Time Frame
1 day
Title
Oral glucose tolerance test
Time Frame
1 day
Title
Mineral metabolism
Description
Blood and urinary calcium, magnesium and phosphate. bone remodeling markers
Time Frame
1 day
Title
Renal fonction
Description
Estimated GFR, proteinuria and albuminuria
Time Frame
1 day
Title
Vascular fonction evaluation
Description
Pulse wave analysis and central blood pressure. Blood and urinary vascular fonction markers
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Gitelman syndrome patients, relatives carrying heterozygous mutations and relatives or healthy voluntarees without mutations.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rosa Vargas-Poussou, MD, PhD
Organizational Affiliation
Departement of Genetics. Assistance Publique Hôpitaux de Paris,Hôpital Européen Georges Pompidou.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anne Blanchard, MD, PhD
Organizational Affiliation
Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou. Paris, France
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Marie Essig, MD, PhD
Organizational Affiliation
Departement of Nephrology. Centre Hospitalier Universitaire. Limoges, France
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jean Philippe Haymann, MD, PhD
Organizational Affiliation
Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ivan Tack, MD, PhD
Organizational Affiliation
Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil. Toulouse, France
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Laurence DUBOURG, MD, PhD
Organizational Affiliation
Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot. Lyon, France
Official's Role
Study Chair
Facility Information:
Facility Name
Nephrology Department. Centre Hospitalier Universitaire, Hôpital Dupuytren
City
Limoges
ZIP/Postal Code
87042 Limoges cedex
Country
France
Facility Name
Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot.
City
Lyon
ZIP/Postal Code
69437 Lyon
Country
France
Facility Name
Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon
City
Paris
ZIP/Postal Code
75020
Country
France
Facility Name
Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou.
City
Paris
ZIP/Postal Code
75908
Country
France
Facility Name
Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil.
City
Toulouse
ZIP/Postal Code
31059 TOULOUSE cedex 9
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
15198479
Citation
Tago N, Kokubo Y, Inamoto N, Naraba H, Tomoike H, Iwai N. A high prevalence of Gitelman's syndrome mutations in Japanese. Hypertens Res. 2004 May;27(5):327-31. doi: 10.1291/hypres.27.327.
Results Reference
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PubMed Identifier
17981812
Citation
Fava C, Montagnana M, Rosberg L, Burri P, Almgren P, Jonsson A, Wanby P, Lippi G, Minuz P, Hulthen LU, Aurell M, Melander O. Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure. Hum Mol Genet. 2008 Feb 1;17(3):413-8. doi: 10.1093/hmg/ddm318. Epub 2007 Nov 1.
Results Reference
background
PubMed Identifier
18391953
Citation
Ji W, Foo JN, O'Roak BJ, Zhao H, Larson MG, Simon DB, Newton-Cheh C, State MW, Levy D, Lifton RP. Rare independent mutations in renal salt handling genes contribute to blood pressure variation. Nat Genet. 2008 May;40(5):592-599. doi: 10.1038/ng.118. Epub 2008 Apr 6.
Results Reference
background
PubMed Identifier
19033254
Citation
Hsu YJ, Yang SS, Chu NF, Sytwu HK, Cheng CJ, Lin SH. Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure. Nephrol Dial Transplant. 2009 Apr;24(4):1170-5. doi: 10.1093/ndt/gfn619. Epub 2008 Nov 25.
Results Reference
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PubMed Identifier
23392128
Citation
Ren H, Qin L, Wang W, Ma J, Zhang W, Shen PY, Shi H, Li X, Chen N. Abnormal glucose metabolism and insulin sensitivity in Chinese patients with Gitelman syndrome. Am J Nephrol. 2013;37(2):152-7. doi: 10.1159/000346708. Epub 2013 Jan 31.
Results Reference
background
PubMed Identifier
11408395
Citation
Cruz DN, Simon DB, Nelson-Williams C, Farhi A, Finberg K, Burleson L, Gill JR, Lifton RP. Mutations in the Na-Cl cotransporter reduce blood pressure in humans. Hypertension. 2001 Jun;37(6):1458-64. doi: 10.1161/01.hyp.37.6.1458.
Results Reference
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Learn more about this trial

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

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