Bone Mass and Strength After Kidney Transplantation

Overview

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.

Full Title of Study: “A Comparative Trial of Calcitriol Versus Placebo for the Preservation of Bone Mass and Strength After Kidney Transplantation”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 12, 2016

Detailed Description

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.

Interventions

  • Drug: Vitamin D3
    • Vitamin D3 1000 IU per day for 12 months
  • Drug: Calcitriol
    • Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months
  • Drug: Placebo
    • Placebo (sugar pill) 1 pill per day for 12 months

Arms, Groups and Cohorts

  • Experimental: Vitamin D3 plus Calcitriol
    • 1 pill of Vitamin D3 (cholecalciferol) 1000 IU daily for 12 months 1 pill of Rocaltrol (calcitriol) 0.5 mcg daily for 12 months
  • Placebo Comparator: Vitamin D3 plus Placebo
    • 1 pill of Vitamin D3 (cholecalciferol) 1000 IU per day for 12 months 1 pill of placebo (sugar pill) per day for 12 months

Clinical Trial Outcome Measures

Primary Measures

  • Percent change in bone quality from pre to post-calcitriol treatment compared to placebo as assessed by both standard methodologies.
    • Time Frame: Baseline, 12 months
    • 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.

Secondary Measures

  • Change in Areal and Volumetric Bone Mass Density from baseline to 12 months after transplantation
    • Time Frame: Baseline, 12 months
    • 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.
  • Percent change in cortical and trabecular bone strength pre- and post-transplantation measured by high resolution imaging methods.
    • Time Frame: Baseline, 12 months
    • Apply advanced imaging methods to determine the influence of calcitriol on cortical and trabecular microarchitecture and strength after kidney transplantation.
  • Percent contribution of cortical porosity to mechanical competence pre- and post-intervention measured by Cortical Porosity Assessment techniques.
    • Time Frame: Baseline, 12 months
    • 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.
  • Changes from baseline to 12 months on vascular calcifications loads of the lower extremity
    • Time Frame: Baseline, 12 months
    • Measured by a novel method applied to HRpQCT datasets.
  • Number of patients with vascular calcifications of the lower extremity
    • Time Frame: Baseline, 12 months
    • Quantification of calcifications of the anterior and posterior tibia arteries measured by a novel method applied to HRpQCT at baseline and 12 months.
  • Change in pre- and post- intervention parathyroid hormone (PTH) levels at baseline,1 month and 12 months after transplantation.
    • Time Frame: Baseline, 1month, 12 months
    • Determine effects of calcitriol on post-transplantation PTH. .
  • 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.
    • Time Frame: Baseline, 1 month, 12 months
    • Determine effects of calcitriol on post-transplantation bone remodeling markers.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Columbia University
  • Collaborator
    • Satellite Healthcare
  • Provider of Information About this Clinical Study
    • Principal Investigator: Thomas Nickolas, MD MS, Associate Professor of Medicine – Columbia University
  • Overall Official(s)
    • Thomas Nickolas, MD, MS, Principal Investigator, Columbia University

References

Iyer SP, Nikkel LE, Nishiyama KK, Dworakowski E, Cremers S, Zhang C, McMahon DJ, Boutroy S, Liu XS, Ratner LE, Cohen DJ, Guo XE, Shane E, Nickolas TL. Kidney transplantation with early corticosteroid withdrawal: paradoxical effects at the central and peripheral skeleton. J Am Soc Nephrol. 2014 Jun;25(6):1331-41. doi: 10.1681/ASN.2013080851. Epub 2014 Feb 7.

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