Official Title: “The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria”

Glomerulonephritis and renal failure represent one of the most life-threatening manifestations of systemic lupus erythematosus (SLE). Although immunosuppressive therapy is often effective for the treatment of acute lupus nephritis, a significant proportion of patients show persistent proteinuria after resolution of the acute nephritic process, and develop progressive renal failure. There is preliminary evidence that calcitriol and other vitamin D analogs can reduce proteinuria in patients with chronic kidney diseases. We plan to conduct a randomized control study to evaluate the safety and efficacy of calcitriol in the treatment of SLE patients with persistent proteinuria. Sixty patients with clinically quiescent SLE and persistent proteinuria despite conventional therapy will be recruited. They will be treated with calcitriol for 48 weeks. Proteinuria, renal function, lupus disease activity, serum and urinary inflammatory markers will be monitored. This study will explore the potential anti-proteinuric and immunomodulating effects of calcitriol in the treatment of SLE, which is a common and life threatening disease in young adults.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2009

Intervention(s) in this Clinical Trial

• Drug: Calcitriol
  • Patients will receive calcitriol (oral capsule) at a fixed dose of 1 mcg twice weekly.
• Drug: Multivitamin
  • Patients will receive multivitamin 1 tab daily (with vitamin D2 300 IU).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: treatment group
  • Patients will receive calcitriol at a fixed dose of 1 mcg twice weekly.
• Active Comparator: control group
  • Patients will receive multivitamin 1 tab daily (with vitamin D2 300 IU).

Primary Measures

• change in proteinuria
  • Time Frame: one year
    Safety Issue?: No

Secondary Measures

• Secondary end points include risk of lupus flare, change in renal function, SLEDAI score, serum and urinary inflammatory markers.
  • Time Frame: one year
    Safety Issue?: Yes

Inclusion Criteria:

• aged 18-65 years
• clinical quiescent SLE for at least 12 weeks
• baseline SLEDAI score <= 4
• history of biopsy-proven lupus nephritis
• estimated glomerular filtration rate 15 to 60 ml/min/1.73m2
• proteinuria > 1 g/day (or proteinuria > 1 g/g-Cr) in 2 consecutive samples within 12 weeks despite ACE inhibitor or angiotensin receptor blocker for at least 3 months
• on maintenance dose of prednisolone < 10 mg/day, with or without other immunosuppressive medications
• corrected serum calcium level < 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 vitamin D analogue
• Patients receiving treatment of vitamin D and/or its analogue for other medical reasons within the past 4 weeks. Patients who are taking multivitamin supplement that contains vitamin D could be enrolled after 4 weeks of wash out period by changing to a preparation that has no vitamin D.
• 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 vitamin D analogs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Chinese University of Hong Kong

Overall Clinical Trial Officials and Contacts

Cheuk-Chun Szeto, MD Principal Investigator Chinese University of Hong Kong  

Overall Contact: Cheuk-Chun Szeto, MD 852-2632-3126 ccszeto@cuhk.edu.hk

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00508898

Study ID Number: CRE-2007.261-T

ClinicalTrials.gov Identifier: NCT00508898

Health Authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee