Paricalcitol for the Treatment of Immunoglobulin A Nephropathy

Paricalcitol for the Treatment of Immunoglobulin A Nephropathy - A Randomized Cross-Over Study

Immunoglobulin A (IgA) nephropathy is the common type of primary glomerulonephritis in the world. A wealth of literature suggests that vitamin D and its analogs have profound effects on immune system function and glomerular mesangial cell proliferation. However, calcitriol, the standard form of vitamin D, carries a substantial risk of hypercalcemia. Recently, paricalcitol (19-nor-1,25-dihydroxyvitamin D2) was approved for the treatment of secondary hyperparathyroidism in chronic renal failure, and the incidence of hypercalcemia is much lower than calcitriol. Therefore, the investigators plan to conduct a randomized cross-over study to evaluate the efficacy of paricalcitol in the treatment of IgA nephropathy. Thirty patients with biopsy-proven IgA nephropathy will be recruited. They will be randomized to paricalcitol for 12 weeks or no treatment, followed by cross over to the other arm after a washout period. Proteinuria, renal function, serum and urinary inflammatory markers will be monitored. This study will explore the potential anti-proteinuric and anti-inflammatory effects of paricalcitol in the treatment of IgA nephropathy, which has no specific treatment at present.

Study Overview

• Status: Withdrawn
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: paricalcitol

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Department of Medicine & Therapeutics, Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 18-65 years
• biopsy-confirmed IgA nephropathy
• proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 3 consecutive samples within 12 weeks despite ACE inhibitor or angiotensin receptor blocker treatment (e.g. ramipril 5 mg daily, lisinopril 10 mg daily, or valsartan 80 mg daily) for at least 3 months
• estimated glomerular filtration rate > 60 ml/min/1.73m2
• corrected serum calcium level > or = 2.45 mmol/l
• willingness to give written consent and comply with the study protocol

Exclusion Criteria:

• 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 paricalcitol
• Patients receiving treatment of vitamin D and/or its analogue for other medical reasons within the past 3 months
• 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 paricalcitol or other vitamin D analogs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; paricalcitol 1 mg/day for 12 weeks, followed by a washout period of 4 weeks, then crossed over to no treatment for another 12 weeks	Drug: paricalcitol; paricalcitol 1 mg/day
Active Comparator: 2; no treatment for 12 weeks, followed by a washout period of 4 weeks, then crossed over to paricalcitol for another 12 weeks	Drug: paricalcitol; paricalcitol 1 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change in the degree of proteinuria	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
rate of decline of estimated GFR (as determined by the least square method) and change in other serum inflammatory markers	12 weeks

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Cheuk Chun Szeto, MD, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): October 1, 2009
• Study Completion (Anticipated): December 1, 2009

Study Registration Dates

• First Submitted: January 2, 2008
• First Submitted That Met QC Criteria: January 14, 2008
• First Posted (Estimate): January 24, 2008

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 31, 2015
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: CRE-2007.409-T