Aliskiren for Immunoglobulin A (IgA) Nephropathy

Study Overview
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Brief Summary
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Immunoglobulin A (IgA) nephropathy is the most common type of primary glomerulonephritis in the world. Current treatment with angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) is not entirely effective. Aliskiren, a direct renin inhibitor, acts on the rate limiting step of the renin-angiotensin axis. In addition to lowering the blood pressure, recent study in diabetic nephropathy suggests an independent anti-proteinuric effect. The investigators plan to conduct a randomized placebo-control cross-over study to evaluate the safety and efficacy of aliskiren in the treatment of IgA nephropathy. The investigators plan to recruit 57 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite conventional therapy. They will be randomized to aliskiren for 16 weeks or no treatment, followed by cross over to the other arm after a washout period. Proteinuria, albuminuria, renal function, serum and urinary markers will be quantified. This study will explore the potential anti-proteinuric effect of aliskiren in the treatment of IgA nephropathy, which has no specific treatment at present.

Official Title
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The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: Aliskiren
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-65 years requires anti-hypertensive therapy renal biopsy within the past 3 years and confirmed the diagnosis of IgA nephropathy proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 3 consecutive samples within 12 weeks despite ACE inhibitor or ARB treatment for at least 3 months estimated glomerular filtration rate > 30 ml/min/1.73m2 willingness to give written consent and comply with the study protocol Exclusion Criteria: Patients who are diabetic, and patients with systemic diseases that may cause IgA nephropathy or another nephropathy. Pregnancy, lactating or childbearing potential without effective method of birth control Severe gastrointestinal disorders that interfere with their ability to receive or absorb oral medication History of malignancy, including leukemia and lymphoma within the past 2 years Systemic infection requiring therapy at study entry Any other severe coexisting disease such as, but not limited to, chronic liver disease, myocardial infarction, cerebrovascular accident, malignant hypertension History of drug or alcohol abuse within past 2 years Participation in any previous trial on aliskiren or other renin inhibitor Previous treatment with fish oil, steroid, cytotoxic agents, or aldosterone antagonist History of treatment with other drugs that may affect proteinuria within past 2 years Patients receiving treatment of corticosteroid On other investigational drugs within last 30 days History of a psychological illness or condition such as to interfere with the patient's ability to understand the requirement of the study History of non-compliance Known history of sensitivity or allergy to aliskiren or other renin inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I<br>each subject will receive oral aliskiren 300 mg/day for 16 weeks, followed by a washout period of 4 weeks, then crossed over to placebo for another 16 weeks | Drug: Aliskiren<br>* Aliskiren 300 mg daily oral<br>Drug: Placebo<br>* starch tablet, 300 mg/day<br>|
| Active Comparator: II<br>each subject will receive placebo for 16 weeks, followed by a washout period of 4 weeks, then crossed over to oral aliskiren 300 mg/day for another 16 weeks | Drug: Aliskiren<br>* Aliskiren 300 mg daily oral<br>Drug: Placebo<br>* starch tablet, 300 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the degree of proteinuria |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of decline of estimated GFR |  | 16 weeks | 
| change in serum and urinary inflammatory markers |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proteinuria, renal failure, glomerulonephritis