Clinical trial NCT00752401: Vitamin D3 Substitution in Vitamin D Deficient Kidney Transplant Recipients
Official title: VITA-D: Cholecalciferol Substitution in Vitamin D Deficient Kidney Transplant Recipients: A Randomized, Placebo-controlled Study to Evaluate the Posttransplant Outcome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Kidney Transplantation
Vitamin D Deficiency
Renal Osteodystrophy
Keywords: Vitamin D
Cholecalciferol
Vitamin D3
25-hydroxyvitamin D3
Immunomodulation
Vitamin D deficiency
Kidney transplantation
Renal transplantation
Graft function
Acute rejection
Renal osteodystrophy
Posttransplant bone loss
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2008-09-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The immunologic effects of Vitamin D3 substitution in vitamin D deficient kidney transplant recipients will be evaluated by means of: Glomerular filtration rate
timeFrame: one year after kidney transplantation
measure: Number of acute rejection episodes
timeFrame: one year after kidney transplantation
measure: Number of infections
timeFrame: one year after kidney transplantation
measure: CRP levels
timeFrame: one year after kidney transplantation
measure: Courses of calcium levels
timeFrame: within the first year after kidney transplantation
Secondary outcomes:
measure: The impact of Vitamin D3 substitution on renal osteopathy will be analyzed by means of absolute bone mineral density (g/cm2)
timeFrame: within the first year after kidney transplantation
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis
Study officials:
affiliation: Medical University of Vienna, Department of Internal Medicine III, Division of Nephrology and Dialysis
name: Kyra Borchhardt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thiem U, Heinze G, Segel R, Perkmann T, Kainberger F, Muhlbacher F, Horl W, Borchhardt K. VITA-D: cholecalciferol substitution in vitamin D deficient kidney transplant recipients: a randomized, placebo-controlled study to evaluate the post-transplant outcome. Trials. 2009 May 29;10:36. doi: 10.1186/1745-6215-10-36.