Clinical trial NCT00870493: Aliskiren for Immunoglobulin A (IgA) Nephropathy
Official title: The Safety and Short-Term Efficacy of Aliskiren in the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: IgA Nephropathy
Keywords: proteinuria
renal failure
glomerulonephritis
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2009-03-27
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: change in the degree of proteinuria
timeFrame: 16 weeks
Secondary outcomes:
measure: rate of decline of estimated GFR
timeFrame: 16 weeks
measure: change in serum and urinary inflammatory markers
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
References:
citation: Szeto CC, Kwan BC, Chow KM, Leung CB, Li PK. The safety and short-term efficacy of aliskiren in the treatment of immunoglobulin a nephropathy--a randomized cross-over study. PLoS One. 2013 May 10;8(5):e62736. doi: 10.1371/journal.pone.0062736. Print 2013.