Vitamin D3 Substitution in Vitamin D Deficient Kidney Transplant Recipients

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effects of Cholecalciferol (Vitamin D3) substitution on the posttransplant outcome (glomerular filtration rate as well as serum creatinine levels, number of acute rejection episodes, number of infections and C-reactive protein levels within the first year after transplantation) in vitamin D deficient kidney transplant recipients.

Detailed Description
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Apart from its classical actions in calcium homeostasis, vitamin D acts as a potent immunomodulatory agent. As such, vitamin D is thought to have beneficial effects in the transplant setting, especially in kidney transplant recipients considering the fact that approximately 40% of all kidney transplant recipients are vitamin D deficient. Therefore, the objective is to conduct a randomized, double-blind, placebo-controlled study focusing on the impact of Cholecalciferol substitution in vitamin D deficient kidney transplant recipients on graft function (glomerular filtration rate as well as serum creatinine levels), incidence of acute rejection episodes, frequency and severity (CRP levels) of posttransplant infections within the first year after kidney transplantation. Moreover, the impact of Vitamin D3 on renal osteodystrophy will be analyzed by means of bone mineral density. DXA measurements will be performed during the first four weeks after kidney transplantation, after 5, and after 12 months posttransplant. Kidney transplant recipients found to have vitamin D deficiency (defined as 25-hydroxyvitamin D < 50 nmol/l) will be included and will be randomized to receive either oral Vitamin D3 therapy or placebo. Vitamin D3 will be administered at a daily dose of 6800IU over a time period of one year. All in all, 200 subjects will be included in the VITA-D study.

Official Title
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VITA-D: Cholecalciferol Substitution in Vitamin D Deficient Kidney Transplant Recipients: A Randomized, Placebo-controlled Study to Evaluate the Posttransplant Outcome

Conditions
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Kidney Transplantation, Vitamin D Deficiency, Renal Osteodystrophy

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 deceased donor kidney transplant recipients only kidney transplant recipients vitamin D deficiency defined as 25 (OH)D < 50nmol/l Exclusion Criteria: re-transplantation for the second time if the patient is highly immunized and therefore included in the aphaeresis program re-transplantation for the third or further time significant impaired intestinal resorption: malabsorption due to celiac sprue, systemic scleroderma; maldigestion due to chronic pancreatitis, pancreatic insufficiency, pancreas resection, mucoviscidosis, Zollinger-Ellison-syndrome history of inflammatory bowel disease: Crohn's disease, ulcerative colitis previous gastrectomy, small bowel or large bowel resection, intestinal bypass surgery severe liver disease: cirrhosis HIV positive

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>6800 IU/day of Cholecalciferol (Vitamin D3) orally for one year | Drug: Cholecalciferol<br>* 6800 IU of Cholecalciferol will be administered in the form of Oleovit® D3-drops once a day for one year. Treatment starts on day 5 after kidney transplantation. At serum calcium levels >2,65 mmol/l vitamin D3 administration will be reduced to 3600 IU per day. If calcium levels persist above 2,85 mmol/l over a period of four weeks vitamin D3 administration will be discontinued and restarted when serum calcium levels declined to ≤ 2,65 mmol/l with only 3600 International Units per day.<br>* Other names: Oleovit® D3;|
| Placebo Comparator: 2<br>Oral placebo solution daily for one year | Drug: Placebo<br>* An oral placebo solution matching Cholecalciferol in terms of appearance, smell and taste will be administered once a day for one year. Treatment starts on day 5 after kidney transplantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The immunologic effects of Vitamin D3 substitution in vitamin D deficient kidney transplant recipients will be evaluated by means of: Glomerular filtration rate |  | one year after kidney transplantation | 
| Number of acute rejection episodes |  | one year after kidney transplantation | 
| Number of infections |  | one year after kidney transplantation | 
| CRP levels |  | one year after kidney transplantation | 
| Courses of calcium levels |  | within the first year after kidney transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of Vitamin D3 substitution on renal osteopathy will be analyzed by means of absolute bone mineral density (g/cm2) |  | within the first year after kidney transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute rejection, Vitamin D, Cholecalciferol, Vitamin D3, 25-hydroxyvitamin D3, Immunomodulation, Vitamin D deficiency, Kidney transplantation, Renal transplantation, Graft function, Renal osteodystrophy, Posttransplant bone loss