A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein

NCT ID: NCT03170336

Last Updated: 2020-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2020-08-01

Brief Summary

Nowadays, the prevalence of chronic kidney disease (CKD) in China is about 10.8%,and nearly 120 million people suffer from CKD, which has become a serious public health problem in China. Study confirmed that proteinuria is an independent risk factor for the continuous deterioration of glomerular filtration rate (GFR) in patients with CKD. So it is of great significance to explore the strategy of reducing proteinuria.

According to our previous study, Amiloride can inhibit the expression of uPAR in podocytes and reduce proteinuria, This clinical trial aims to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with Chronic Kidney Disease.

Detailed Description

Amiloride is a Na+ channel blocker and has been used as a diuretic. It mainly inhibits the exchange of Na+-K+ and Na+-H+ in the distal tubule and collecting duct of the kidney, thus increasing the excretion of Na+ and water, reducing the excretion of K+ and H+. Recent studies have found a significant increase in urine uPA in patients with massive proteinuria.Urine uPA concentration were positively correlated with urinary protein and decreased with remission of proteinuria. In children and adults with nephrotic syndrome,as well as rat with proteinuria induced by puromycin amino-nucleoside, amiloride can inhibit uPA concentration in urine, which may be one of the mechanisms of amiloride in reducing proteinuria.

This study is a prospective , crossover, open-Label study. All patients need to be on an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) daily at least four weeks prior to the study. The baseline data would be recorded. Patients enrolled will receive either amiloride or hydrochlorothiazide first for 8 weeks.Hydrochlorothiazide, a similar diuretic as amiloride, but not inhibiting urokinase plasminogen activator receptor (uPAR), will be used as a control. Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with the ACE inhibitor or ARB. After that patients will cross over to receive another medication for another 8 weeks. We aim to evaluate the effect and safety of Amiloride in decreasing proteinuria for patients with chronic kidney disease.

Conditions

Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

amiloride

Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks

Group Type: EXPERIMENTAL

Amiloride

Intervention Type: DRUG

Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks.

hydrochlorothiazide

hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.

Group Type: ACTIVE_COMPARATOR

Hydrochlorothiazide

Intervention Type: DRUG

hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.

Interventions

Amiloride

Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks.

Intervention Type: DRUG

Hydrochlorothiazide

hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients at the age of more than 14 years old with chronic kidney disease
• Good compliance of treatment
• PCR≥500mg/g.cr ，more than double confirmed
• Patients who written informed consent

Exclusion Criteria

• less than 14 years of age
• eGFR≤30ml/min.1.73m2；
• poor compliance of treatment
• Previously intolerant or allergic to hydrochlorothiazide
• Patients with history of gout within six months
• Patients with active infection
• Patients with severe cardiopulmonary disease and dysfunction of central nervous system
• history of malignancy
• life expectancy is less than 1 years
• women who are pregnant,lactating and lack of contraception.
• enrolled in other clinical trials within 3 months
• patients who have used immunosuppressive agents or corticosteroids recently or in the past 12 weeks.
• patients without informed consent written or who enable or unwilling to comply with protocol approved by researchers.

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nephrology Dept,Guangdong General Hospital

Guangzhou, Guangdong, China

Countries

China

Other Identifiers

GGH2016422H

Identifier Type: -

Identifier Source: org_study_id