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A New Application of Amiloride in the Treatment of Patient With Chronic Kidney Disease In Reducing Urinary PROtein (ANTI-UPRO)

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ClinicalTrials.gov Identifier: NCT03170336
Recruitment Status : Recruiting
First Posted : May 31, 2017
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Guangdong General Hospital

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.


Condition or disease Intervention/treatment Phase
Chronic Kidney Diseases Drug: Amiloride Drug: Hydrochlorothiazide Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: 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.Then the patients will discontinue amiloride or hydrochlorothiazide for a washout for 4 weeks, but continue with ACEI(angiotensin-converting enzyme inhibitor ) or ARB. After that patients will cross over to receive another medication for another 8 weeks.
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effect and Safety of Amiloride in Decreasing Proteinuria for Patients With Chronic Kidney Disease in a Prospective , Crossover, Open-label Study.
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : June 1, 2019
Estimated Study Completion Date : June 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: amiloride
Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks
Drug: Amiloride
Amiloride first for 8 weeks, then for a washout for 4 weeks, and cross over to receive hydrochlorothiazide for another 8 weeks.

Active Comparator: hydrochlorothiazide
hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.
Drug: Hydrochlorothiazide
hydrochlorothiazide first for 8 weeks, then for a washout for 4 weeks, and cross over to receive amiloride for another 8 weeks.




Primary Outcome Measures :
  1. The remission of proteinuria [ Time Frame: after treatment for 12 weeks ]

Secondary Outcome Measures :
  1. estimated Glomerular Filtration Rate [ Time Frame: after treatment for 12 weeks ]
    time to a 50% reduction in baseline estimated Glomerular filtration rate (according to CKD-EPI) and to doubling of baseline creatinine

  2. creatinine [ Time Frame: after treatment for 12 weeks ]
    time to doubling of baseline creatinine

  3. hyperkalemia [ Time Frame: at 12 weeks after treatment ]
    The ratio of hyperkalemia occurred at 12 weeks after treatment.



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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03170336


Contacts
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Contact: xinling Liang, M.D.,PH.D 13808819770 xinlingliang_ggh@163.com

Locations
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China, Guangdong
Nephrology Dept,Guangdong General Hospital Recruiting
Guangzhou, Guangdong, China
Contact: Liang Xinling, MD,PhD    86-13808819770    xinlingliang_ggh@163.com   
Sponsors and Collaborators
Guangdong General Hospital

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Responsible Party: Guangdong General Hospital
ClinicalTrials.gov Identifier: NCT03170336     History of Changes
Other Study ID Numbers: GGH2016422H
First Posted: May 31, 2017    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hydrochlorothiazide
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Amiloride
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing