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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-31

Study Completion Date

2016-09-30

Brief Summary

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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.

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Detailed Description

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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).

Conditions

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Heterozygous Carriers of Gitelman Syndrome

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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study's population

Group Type OTHER

Samplings of blood

Intervention Type PROCEDURE

Sampling of urine

Intervention Type PROCEDURE

Measure of the blood pressure

Intervention Type PROCEDURE

glycemia test

Intervention Type PROCEDURE

Interventions

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Samplings of blood

Intervention Type PROCEDURE

Sampling of urine

Intervention Type PROCEDURE

Measure of the blood pressure

Intervention Type PROCEDURE

glycemia test

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

Gitelman syndrome patients, relatives carrying heterozygous mutations and relatives or healthy voluntarees without mutations.

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rosa Vargas-Poussou, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Departement of Genetics. Assistance Publique Hôpitaux de Paris,Hôpital Européen Georges Pompidou.

Anne Blanchard, MD, PhD

Role: STUDY_DIRECTOR

Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou. Paris, France

Marie Essig, MD, PhD

Role: STUDY_CHAIR

Departement of Nephrology. Centre Hospitalier Universitaire. Limoges, France

Jean Philippe Haymann, MD, PhD

Role: STUDY_CHAIR

Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon, Paris, France

Ivan Tack, MD, PhD

Role: STUDY_CHAIR

Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil. Toulouse, France

Laurence DUBOURG, MD, PhD

Role: STUDY_CHAIR

Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot. Lyon, France

Locations

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Nephrology Department. Centre Hospitalier Universitaire, Hôpital Dupuytren

Limoges, , France

Site Status

Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot.

Lyon, , France

Site Status

Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon

Paris, , France

Site Status

Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou.

Paris, , France

Site Status

Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil.

Toulouse, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND

PMID: 15198479 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 17981812 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 18391953 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 19033254 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 23392128 (View on PubMed)

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.

Reference Type BACKGROUND

PMID: 11408395 (View on PubMed)

Other Identifiers

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P120111

Identifier Type: -

Identifier Source: org_study_id

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

Study Results

Basic Information

Brief Summary

Related Clinical Trials

Polymorphisms of the Thiazide's Receptor Gene SLC12A3 and Development of Hyponatremia

Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia

Salt Supplementation in Gitelman Syndrome

Analyzing Genetic Factors Involved in Blood Pressure Changes Due to Salt and Potassium Intake (The GenSalt Study)

Genetic Based Analysis in Hypertensive Patients

Detailed Description

Conditions

Study Design

Study Groups

study's population

Samplings of blood

Sampling of urine

Measure of the blood pressure

glycemia test

Interventions

Samplings of blood

Sampling of urine

Measure of the blood pressure

glycemia test

Eligibility Criteria

Inclusion Criteria

Sponsors

Ministry of Health, France

Assistance Publique - Hôpitaux de Paris

Responsible Party

Principal Investigators

Rosa Vargas-Poussou, MD, PhD

Anne Blanchard, MD, PhD

Marie Essig, MD, PhD

Jean Philippe Haymann, MD, PhD

Ivan Tack, MD, PhD

Laurence DUBOURG, MD, PhD

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.

Countries

References

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.

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.

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.

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.

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.

Other Identifiers

P120111

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