Specific Blockage of Angiotensine 2 and Podocyturia in Glomerular Nephropathies With Hypertension and Proteinuria

NCT00369538 | Suspended Phase 4

• 1 other identifier: 3742
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic glomerular diseases are one of the main causes leading to end stage renal disease (ESRD). Hypertension and proteinuria are two modifiable factors promoting the progression of ESRD. Podocyte are terminally differentiated epithelial cells and play a central role in the progression of chronic kidney disease and in the development of glomerulosclerosis. The presence of podocyte in urines (podocyturia) has been documented by several teams with continuous and regular podocyturia during glomerular disease. This facts suggests that podocyturia could become a marker of podocyte loss and glomerular damage. In our university hospital, we developed a technique to evaluate the number of microparticles (cellular fragments) in different biologic samples. The podocytary origin of microparticles will be determinated thanks to specific antibodies. The aim of the present study is: i) to quantify podocyturia during glomerular nephropathies by dosing podocyte microparticles ii) to study the relationship between podocyturia and other biologic markers such as proteinuria iii) to evaluate the effect of angiotensine 2 blockage on podocyturia. This is an open-labelled randomized monocenter cross-over study. Twenty subjects with hypertension and glomerular nephropathy characterized by proteinuria and a normal or slightly altered renal function will be included. Patients will be treated successively by an angiotensin receptor blocker (ARB), losartan and by a thiazide, hydrochlorothiazide, (after a wash out period). We will study the impact of these two therapies on podocyturia. Results will be compared with others markers like proteinuria (and its selectivity). We may finally dispose of a non invasive urinary marker of podocyte lesions responsible for glomerulosclerosis and for ESRD progression. Moreover mechanism of nephroprotection of the ARB may be more comprehensive.

Conditions

Proteinuria; Hypertension; End Stage Renal Disease

Keywords

Podocyte - podocyturia - microparticles - angiotensin receptor antagonist - glomerulosclerosis; Patients presenting with stable glomerular nephropathy with proteinuria, normal or slightly altered renal function, with hypertension

Outcome Measures

Primary Outcomes (1)

• Podocyturia

Secondary Outcomes (3)

• Proteinuria;

• selectivity index of proteinuria

• arterial blood pressure

Study Arms (2)

1

ACTIVE COMPARATOR

losartan, hydrochlorothiazide

Drug: losartan, hydrochlorothiazide

2

ACTIVE COMPARATOR

hydrochlorothiazide, losartan

Drug: hydrochlorothiazide, losartan

Interventions

losartan, hydrochlorothiazide DRUG

Two administrations of losartan per day,up to 100mg per day, during 2 months, followed by a wash-out during 1 month, and then one administration of hydrochlorothiazide, 25 mg per day during 2 months

1

hydrochlorothiazide, losartan DRUG

One administration of hydrochlorothiazide, 25 mg per day during 2 months, followed by a wash-out during 1 month, and then, two administrations of losartan per day,up to 100mg per day, during 2 months

2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

* Hypertension (TAs \> 130, TAd \> 80mmHg or under antihypertensive treatment) * Glomerular nephropathy, proteinuria \> 1 g/day, serum creatinin \< 200 µmol/L ; * Informed consent given ; * No contraindication for ARB and hydrochlorothiazide ; * Efficient contraception for women

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Service de Néphrologie, Hôpital Civil, Hôpitaux Universitaires

Strasbourg, 67091, France

Location

MeSH Terms

Conditions

Proteinuria; Hypertension; Kidney Failure, Chronic

Interventions

hydrochlorothiazide, losartan drug combination

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Study Officials

• Luc FRANTZEN, MD

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 28, 2006
• First Posted: August 29, 2006
• Study Start: August 1, 2006
• Last Updated: February 18, 2009

Record last verified: 2009-02

Locations

FR (1)