Bone Mass and Strength After Kidney Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to test whether active vitamin D (calcitriol) protects bones from weakening and protects blood vessels from calcium deposits over the first year of kidney transplantation.

Detailed Description
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Kidney transplant recipients at highest fracture risk, as determined by epidemiologic studies (Caucasians and older recipients). Rocaltrol (calcitriol) is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body.

Official Title
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A Comparative Trial of Calcitriol Versus Placebo for the Preservation of Bone Mass and Strength After Kidney Transplantation

Conditions
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End Stage Renal Disease, Kidney Transplantation, Bone Loss, Fractures, Vascular Calcifications

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Calcitriol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age older than 18 Self-describes as White race Exclusion Criteria: Lower extremity amputations Non-ambulatory Paget´s disease of bone Current hyperthyroidism, untreated hypothyroidism Medical diseases (end stage liver, intestinal malabsorption) Use within the prior year pod anti-seizure medications that induce the cytochrome P450 system, testosterone, estrogen, selective estrogen receptor modulators Weight >300 pounds Dual organ transplant Myocardial infarction or stroke Tobacco use within the past year

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 plus Calcitriol<br>1 pill of Vitamin D3 (cholecalciferol) 1000 IU daily for 12 months 1 pill of Rocaltrol (calcitriol) 0.5 mcg daily for 12 months | Drug: Vitamin D3<br>* Vitamin D3 1000 IU per day for 12 months<br>* Other names: cholecalciferol;Drug: Calcitriol<br>* Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months<br>* Other names: Rocaltrol;|
| Placebo Comparator: Vitamin D3 plus Placebo<br>1 pill of Vitamin D3 (cholecalciferol) 1000 IU per day for 12 months 1 pill of placebo (sugar pill) per day for 12 months | Drug: Vitamin D3<br>* Vitamin D3 1000 IU per day for 12 months<br>* Other names: cholecalciferol;Drug: Placebo<br>* Placebo (sugar pill) 1 pill per day for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in bone quality from pre to post-calcitriol treatment compared to placebo as assessed by both standard methodologies. | Novel high resolution bone imaging can separately measure and quantify cortical and trabecular responses to bone active treatments. Finite element analysis (FEA) can be applied to HRpQCT datasets. to provide a computational estimate of bone mechanical competence that has been validated against true compressive tests of bone stiffness and strength. | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Areal and Volumetric Bone Mass Density from baseline to 12 months after transplantation | Apply imaging methods to shed light on whether preservation of areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) is accompanied by preservation of bone mechanical competence measured by a method that has been validated against true compressive tests of bone strength. | Baseline, 12 months | 
| Percent change in cortical and trabecular bone strength pre- and post-transplantation measured by high resolution imaging methods. | Apply advanced imaging methods to determine the influence of calcitriol on cortical and trabecular microarchitecture and strength after kidney transplantation. | Baseline, 12 months | 
| Percent contribution of cortical porosity to mechanical competence pre- and post-intervention measured by Cortical Porosity Assessment techniques. | Apply Cortical Porosity Assessment techniques to high resolution peripheral quantitative computed tomography (HRpQCT) scans to quantify the contribution of cortical porosity to mechanical competence in kidney transplant patients both pre- and post-calcitriol treatment compared to placebo. | Baseline, 12 months | 
| Changes from baseline to 12 months on vascular calcifications loads of the lower extremity | Measured by a novel method applied to HRpQCT datasets. | Baseline, 12 months | 
| Number of patients with vascular calcifications of the lower extremity | Quantification of calcifications of the anterior and posterior tibia arteries measured by a novel method applied to HRpQCT at baseline and 12 months. | Baseline, 12 months | 
| Change in pre- and post- intervention parathyroid hormone (PTH) levels at baseline,1 month and 12 months after transplantation. | Determine effects of calcitriol on post-transplantation PTH. . | Baseline, 1month, 12 months | 
| Change in pre- and post- intervention levels of bone remodeling markers for bone remodeling assessment from baseline to 1 month and 12 months after transplantation. | Determine effects of calcitriol on post-transplantation bone remodeling markers. | Baseline, 1 month, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney Transplantation, Calcitriol, Bone Mineral Density, Bone Mass and Strength, Vascular Calcifications, Hyperparathyroidism, Parathyroid Hormone