Optimalization of Nephroprotection Using N-Acetylcysteine

Chronic Kidney Disease Clinical Trial

Official title:

The Effect of N-Acetylcysteine on Proteinuria and Markers of Tubular Injury in Non-Diabetic Patientswith Chronic Kidney Disease-Placebo Controlled, Randomized,Open, Cross-Over Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00572663
• Other study ID #: ST-4/NAC/01
• Status: Completed
• Phase: N/A
• First received: December 12, 2007
• Last updated: December 12, 2007
• Start date: January 2005

Study information

• Verified date: December 2007
• Source: Medical University of Gdansk
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The main purpose of the study is find whether the addition of N-acetylcysteine (antioxidant) to dual renin-angiotensin-aldosterone system blockade involving angiotensin converting enzyme inhibitor and AT-1 angiotensin II receptor blocker leads to the reduction of proteinuria, main prognostic marker of chronic kidney disease progression.

Description:

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney diseases (CKD), and inhibition of the RAAS with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) may retard CKD progression. Dual pharmacological blockade of the RAAS with ACEI and ARB is recommended as a standard renoprotective management at least in patients with nondiabetic proteinuric CKD. However, neither ACEI nor ARB, even in high doses or in concomitant usage, abrogate the progression of CKD completely. Innovative approaches are needed to keep patients with CKD off dialysis. Additional antioxidant (N-acetylcysteine) may prove to be such beneficial therapeutic concept. To shed more light on this issue, we performed a randomised open controlled study to evaluate the influence of triple N-acetylcysteine and RAAS therapy on surrogate markers of kidney injury, i.e. proteinuria, markers of tubular involvement and kidney fibrosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Chronic kidney disease

• Stable proteinuria above 300 mg/24 hours (no variations above 25% in the last 6 months)

• Normal or slightly impaired stable renal function defined as serum creatinine level below 1.7 mg/dl (eGFR > 45 ml/min)

Exclusion Criteria:

• Nephrotic syndrome

• Steroids or other immunosuppressive treatment minimum during six months before the study

• Diabetes mellitus

• Potassium serum level > 5.1 mEq/L

• Albumin serum level < 2.0mg/dL

• Creatinine serum level >2 mg/dl

• Current diagnosis of heart failure New York Heart Association (NYHA) Class II-IV

• Clinically significant valvular heart disease or second or third degree heart block without a pacemaker

• History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack

• History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention

• History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years

• Pregnant or nursing women

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs.

• History of alcohol abuse

• NSAID abuse (more than 2 doses per week)

• Known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors, AT-1 receptor blockers and N-acetylcysteine

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Proteinuria
• Renal Insufficiency, Chronic

Intervention

Drug:
• ACC (N-acetylcysteine) 1200 mg
N-acetylcysteine (ACC) 1200 mg In the 8-weeks run-in period angiotensin converting enzyme inhibitors and/or angiotensin II subtype 1 receptor antagonists were administered to achieve the target blood pressure below 130/80 mmHg. Next, they were randomly assigned to add (or not) 1200 mg N-acetylcysteine in two active treatment periods lasting 8 weeks each

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Gdansk

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigate the antiproteinuric effect of adding antioxidant, N-acetylcysteine to the combination therapy with angiotensin converting enzyme inhibitor and AT-1 receptor blocker in maximal recommended doses.
Secondary	Investigate the effect of the study intervention on urine excretion of N-acetyl-ß-D-glucosaminidase, alfa1-microglobulin and amino-terminal propeptide of type III procollagen