Ignite Creation Date:
2024-05-05 @ 4:46 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00319761
Status:
COMPLETED
Last Update Posted:
2009-01-30
First Post:
2006-04-27
Brief Title:
Calcitriol in the Treatment of Immunoglobulin A IgA Nephropathy
Sponsor:
Chinese University of Hong Kong
Organization:
Chinese University of Hong Kong
Study Overview
Official Title:
The Safety and Short-Term Efficacy of Calcitriol in the Treatment of Immunoglobulin A Nephropathy
Status:
COMPLETED
Status Verified Date:
2009-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Immunoglobulin A IgA nephropathy is the most 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 Calcitriol an active form of vitamin D is commonly used for the treatment of secondary hyperparathyroidism in patients with advanced chronic kidney diseases Therefore the investigators plan to conduct a open-label single-arm study to evaluate the safety and efficacy of calcitriol in the treatment of IgA nephropathy Ten patients with biopsy-proven IgA nephropathy and persistent proteinuria despite conventional therapy will be recruited They will be treated with calcitriol for 12 weeks Proteinuria renal function serum and urinary inflammatory markers will be monitored This study will explore the potential anti-proteinuric and anti-inflammatory effects of calcitriol in the treatment of IgA nephropathy which is a major cause of dialysis-dependent renal failure
Detailed Description:
This is a open-label and single arm study We plan to recruit 10 patients with biopsy-proven IgA nephropathy will be recruited
Treatment regimen and dosage adjustment
At week 0 all patients will receive calcitriol oral capsule at a fixed dose of 05 mcg twice weekly If there is no adverse effect and corrected serum calcium remains 255 mmoll the dose of calcitriol will be maintained for 12 weeks
If corrected serum calcium is 255 to 262 mmoll the dose of calcitriol will be reduced to 025 mcg twice weekly Serum calcium will be rechecked after 2 weeks or more frequently if indicated If corrected serum calcium remains 255 mmoll the dose of calcitriol will be maintained for the rest of the study period If corrected serum calcium remains 262 mmoll for two consecutive measurements despite reducing the dose of calcitriol the study medication will be stopped and the subject will be discontinued from the study
If corrected serum calcium is 275 mmoll at any time hold calcitriol for one week and repeat laboratory test for calcium If the subjects next serum calcium is 262 mmoll calcitriol may be restarted at 025 mcg twice weekly If the next serum calcium level is 262 mmoll the subject will be discontinued from the study
Concomitant therapy
Prior to enrollment all of the patients will be stable while receiving ACE inhibitor or angiotensin receptor blocker Anti-hypertensive therapy will be titrated throughout the study period to maintain the blood pressure below 130 80 mmHg
Visit schedule
Follow up visits will take place according to the following schedule
week -4 screening
weeks 0 start calcitriol 2 4 6 8 12 stop calcitriol and 16
During every visit the following parameters will be measured body weight blood pressure pulse adverse effects of treatment complete blood picture differential white cell count renal function test liver enzymes serum calcium phosphate and early morning urine collection for protein-to-creatinine ratio Renal function is determined by the estimated glomerular filtration rate GFR according to a standardized formula 20 Serum fasting glucose and lipid profile will be measured at 0 and 12 weeks
In order to examine the anti-proliferative and anti-inflammatory action of calcitriol serum level of C-reactive protein CRP interleukin-6 IL-6 and transforming growth factor-beta TGF and urinary levels of TGF hepatocyte growth factor HGF monocyte chemoattractant protein-1 MCP-1 and thrombospondin-1 TSP-1 will be measured at 0 4 12 and 16 weeks by ELISA The above panel of cytokine is chosen because of their documented relevance in IgA nephropathy and progressive renal failure 161921-27
End points
Primary end point of the study is the change in the degree of proteinuria Secondary end points include the change in renal function and other serum inflammatory markers
Adverse events
Information about every adverse event will be collected and recorded An adverse event is any undesirable symptom or medical condition occurring after starting the study medication whether considered drug-related or not
Patient withdrawal
The patient will be withdrawn from the study for
death
doubling of baseline serum creatinine level
pregnancy
hypercalcemia serum calcium 262 mmolL for two consecutive measurements
any other intolerable adverse events
significant non-compliance with the protocol
the desire of the patient to withdraw from the study All female patients will be advised on taking effective contraceptive measures during the study period
Treatment regimen and dosage adjustment
At week 0 all patients will receive calcitriol oral capsule at a fixed dose of 05 mcg twice weekly If there is no adverse effect and corrected serum calcium remains 255 mmoll the dose of calcitriol will be maintained for 12 weeks
If corrected serum calcium is 255 to 262 mmoll the dose of calcitriol will be reduced to 025 mcg twice weekly Serum calcium will be rechecked after 2 weeks or more frequently if indicated If corrected serum calcium remains 255 mmoll the dose of calcitriol will be maintained for the rest of the study period If corrected serum calcium remains 262 mmoll for two consecutive measurements despite reducing the dose of calcitriol the study medication will be stopped and the subject will be discontinued from the study
If corrected serum calcium is 275 mmoll at any time hold calcitriol for one week and repeat laboratory test for calcium If the subjects next serum calcium is 262 mmoll calcitriol may be restarted at 025 mcg twice weekly If the next serum calcium level is 262 mmoll the subject will be discontinued from the study
Concomitant therapy
Prior to enrollment all of the patients will be stable while receiving ACE inhibitor or angiotensin receptor blocker Anti-hypertensive therapy will be titrated throughout the study period to maintain the blood pressure below 130 80 mmHg
Visit schedule
Follow up visits will take place according to the following schedule
week -4 screening
weeks 0 start calcitriol 2 4 6 8 12 stop calcitriol and 16
During every visit the following parameters will be measured body weight blood pressure pulse adverse effects of treatment complete blood picture differential white cell count renal function test liver enzymes serum calcium phosphate and early morning urine collection for protein-to-creatinine ratio Renal function is determined by the estimated glomerular filtration rate GFR according to a standardized formula 20 Serum fasting glucose and lipid profile will be measured at 0 and 12 weeks
In order to examine the anti-proliferative and anti-inflammatory action of calcitriol serum level of C-reactive protein CRP interleukin-6 IL-6 and transforming growth factor-beta TGF and urinary levels of TGF hepatocyte growth factor HGF monocyte chemoattractant protein-1 MCP-1 and thrombospondin-1 TSP-1 will be measured at 0 4 12 and 16 weeks by ELISA The above panel of cytokine is chosen because of their documented relevance in IgA nephropathy and progressive renal failure 161921-27
End points
Primary end point of the study is the change in the degree of proteinuria Secondary end points include the change in renal function and other serum inflammatory markers
Adverse events
Information about every adverse event will be collected and recorded An adverse event is any undesirable symptom or medical condition occurring after starting the study medication whether considered drug-related or not
Patient withdrawal
The patient will be withdrawn from the study for
death
doubling of baseline serum creatinine level
pregnancy
hypercalcemia serum calcium 262 mmolL for two consecutive measurements
any other intolerable adverse events
significant non-compliance with the protocol
the desire of the patient to withdraw from the study All female patients will be advised on taking effective contraceptive measures during the study period
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None