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2025-12-24 @ 12:03 PM
Ignite Modification Date:
2025-12-27 @ 10:41 PM
Study NCT ID:
NCT00319761
Status:
COMPLETED
Last Update Posted:
2009-01-30
First Post:
2006-04-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Calcitriol in the Treatment of Immunoglobulin A (IgA) Nephropathy
Sponsor:
Chinese University of Hong Kong
Organization:
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 0.5 mcg twice weekly. If there is no adverse effect and corrected serum calcium remains \< 2.55 mmol/l, the dose of calcitriol will be maintained for 12 weeks.
If corrected serum calcium is 2.55 to 2.62 mmol/l, the dose of calcitriol will be reduced to 0.25 mcg twice weekly. Serum calcium will be rechecked after 2 weeks (or more frequently if indicated). If corrected serum calcium remains \< 2.55 mmol/l, the dose of calcitriol will be maintained for the rest of the study period. If corrected serum calcium remains \> 2.62 mmol/l 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 \> 2.75 mmol/l at any time, hold calcitriol for one week and repeat laboratory test for calcium. If the subject's next serum calcium is \< 2.62 mmol/l, calcitriol may be restarted at 0.25 mcg twice weekly. If the next serum calcium level is \> 2.62 mmol/l, 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 \[16,19,21-27\].
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 \> 2.62 mmol/L 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 0.5 mcg twice weekly. If there is no adverse effect and corrected serum calcium remains \< 2.55 mmol/l, the dose of calcitriol will be maintained for 12 weeks.
If corrected serum calcium is 2.55 to 2.62 mmol/l, the dose of calcitriol will be reduced to 0.25 mcg twice weekly. Serum calcium will be rechecked after 2 weeks (or more frequently if indicated). If corrected serum calcium remains \< 2.55 mmol/l, the dose of calcitriol will be maintained for the rest of the study period. If corrected serum calcium remains \> 2.62 mmol/l 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 \> 2.75 mmol/l at any time, hold calcitriol for one week and repeat laboratory test for calcium. If the subject's next serum calcium is \< 2.62 mmol/l, calcitriol may be restarted at 0.25 mcg twice weekly. If the next serum calcium level is \> 2.62 mmol/l, 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 \[16,19,21-27\].
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 \> 2.62 mmol/L 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:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: