Heterozygous Carriers of Gitelman SyndromeHEPHYGINCT02035046

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

A study testing Samplings of blood, Sampling of urine and Measure of the blood pressure in people with Heterozygous Carriers of Gitelman Syndrome, run by Assistance Publique - Hôpitaux de Paris at 5 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Heterozygous Carriers of Gitelman Syndrome
What is being tested?: Samplings of blood, Sampling of urine and Measure of the blood pressure
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 250 participants
Where: 5 sitesFrance
Study dates: Dec 2013to Sep 2016
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

France5 sites

Nephrology Department. Centre Hospitalier Universitaire, Hôpital Dupuytren
Limoges, 87042 Limoges cedex
Department of Functional Investigations. Hospices Civils de Lyon, Hôpital Edouard Herriot.
Lyon, 69437 Lyon
Department of Functional Investigations. Assistance Publique Hôpitaux de Paris, Hôpital Tenon
Paris, 75020
Clinical Research Center. Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou.
Paris, 75908
Department of Functional Investigations. Centre Hospitalier Universitaire, Hôpital de Rangueil.
Toulouse, 31059 TOULOUSE cedex 9

Other trials in France

About this study

Read the 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).

Conditions: Heterozygous Carriers of Gitelman Syndrome
Being tested: Samplings of blood, Sampling of urine, Measure of the blood pressure, glycemia test
Keywords: Gitelman, Heterozygous SLC12A3 mutation, Blood pressure, Hypokalemia
Medical subject headings: Hypokalemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Samplings of bloodProcedure or surgery
Sampling of urineProcedure or surgery
Measure of the blood pressureProcedure or surgery
glycemia testProcedure or surgery

Study groups in NCT02035046
Study group	Role	What they receive
study's population	Other	Not described Receives: Procedure: Samplings of blood; Procedure: Sampling of urine; Procedure: Measure of the blood pressure; Procedure: glycemia test

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (7)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2013Sep 2016

First posted14 Jan 2014 (estimated)
Study startDec 2013
Primary completionSep 2016
Study completionSep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Heterozygous Carriers of Gitelman SyndromeStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 250 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02035046
Sponsor's protocol ID: P120111
Acronym: HEPHYGI
Status last verified: Jan 2017
First submitted: 18 Dec 2013
Last updated: 16 Jan 2017
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 15198479
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.
PubMed 17981812
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.
PubMed 18391953
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.
PubMed 19033254
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.
PubMed 23392128
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.
PubMed 11408395

Study at a glance

From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Significance of Heterozygosity for Mutations of the SLC12A3 Gene Coding for the Thiazide Sensitive Na-Cl Cotransporter
ClinicalTrials.gov ID: NCT02035046
Acronym / sponsor ID: HEPHYGI / P120111
Conditions: Heterozygous Carriers of Gitelman Syndrome
Keywords: Gitelman, Heterozygous SLC12A3 mutation, Blood pressure, Hypokalemia
Study type: Interventional
Recruitment status: Completed
Enrolment: 250 participants (estimated)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Collaborators: Ministry of Health, France
Study start: Dec 2013
Primary completion: Sep 2016 (actual)
Study completion: Sep 2016 (actual)
First posted: 14 Jan 2014 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
study's population	Other	Procedure: Samplings of blood, Procedure: Sampling of urine, Procedure: Measure of the blood pressure, Procedure: glycemia test

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Samplings of blood	Procedure or surgery	study's population
Sampling of urine	Procedure or surgery	study's population
Measure of the blood pressure	Procedure or surgery	study's population
glycemia test	Procedure or surgery	study's population

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

7 secondary outcomes

Salt balance
Time frame: 1 day
Potassium metabolism
Time frame: 1 day
Glucose and lipide metabolism
Time frame: 1 day
Oral glucose tolerance test
Time frame: 1 day
Mineral metabolism
Time frame: 1 day
Renal fonction
Time frame: 1 day
Vascular fonction evaluation
Time frame: 1 day

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
Background: PubMed 15198479Tago 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.
Background: PubMed 17981812Fava 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.
Background: PubMed 18391953Ji 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.
Background: PubMed 19033254Hsu 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.
Background: PubMed 23392128Ren 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.
Background: PubMed 11408395Cruz 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Rosa Vargas-Poussou, MD, PhD principal investigator

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

Anne Blanchard, MD, PhD study director

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

Marie Essig, MD, PhD study chair

Departement of Nephrology. Centre Hospitalier Universitaire. Limoges, France

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Systolic blood pressure evaluated by self-measurement (time frame: 3 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02035046, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2017.