Bone Mass and Strength After Kidney Transplantation

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; Kidney Transplantation; Bone Loss; Fractures; Vascular Calcifications
• Intervention / Treatment: Drug: Vitamin D3; Drug: Calcitriol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Vitamin D3; Vitamin D3 1000 IU per day for 12 months; Other Names: cholecalciferol; Drug: Calcitriol; Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months; Other Names: Rocaltrol
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	Drug: Vitamin D3; Vitamin D3 1000 IU per day for 12 months; Other Names: cholecalciferol; Drug: Placebo; Placebo (sugar pill) 1 pill per day for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Bone Density 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
Percent Change in Areal 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 Failure Load Pre- and Post-transplantation Measured by High Resolution Imaging Methods	Failure load refers to the maximum amount of force a bone can withstand before it fractures. Volumetric BMD and microarchitecture of cortical and trabecular compartments were measured using HR-pQCT first- (XCT1) and second-generation scanners (XCT2), with voxel size 82 μm and 60 μm respectively. HR-pQCT imaging was performed on the non-dominant radius and tibia.	Baseline, 12 months
Percent Change of Cortical Porosity Pre- and Post-intervention	Cortical porosity was calculated as the percentage of void space in the cortex. HR-pQCT imaging was performed on the non-dominant radius and tibia.	Baseline, 12 months
Percent Change in Vascular Calcifications Loads of the Lower Extremity	A semi-automated algorithm implemented in image processing language was used for assessment of lower leg arterial calcification (LLAC) and wrist arterial calcification (WAC).	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
Percent Change in Pre- and Post- Intervention Parathyroid Hormone (PTH) Levels	PTH levels were measured in participants to confirm the hypothesis that calcitriol administration over the first year of kidney transplantation would protect the cortical skeleton in recipients managed without corticosteroids due to its ability to suppress PTH and bone remodeling.	Baseline, 12 months
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment	Participants underwent a blood draw for measurement of bone markers: bone-specific alkaline phosphatase (BSAP), propeptide of type 1 procollagen (P1NP), osteocalcin (OC), and the bone resorption marker serum cross-linked C-telopeptide of type I collagen (CTX).	Baseline, 12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Satellite Healthcare
• Investigators: Principal Investigator: Thomas Nickolas, MD, MS, Columbia University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2014
• Primary Completion (Actual): October 12, 2016
• Study Completion (Actual): October 12, 2016

Study Registration Dates

• First Submitted: August 22, 2014
• First Submitted That Met QC Criteria: August 22, 2014
• First Posted (Estimated): August 25, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Hyperparathyroidism; Parathyroid Hormone; Bone Mineral Density; Calcitriol; Vascular Calcifications; Bone Mass and Strength
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Calcium Metabolism Disorders; Kidney Failure, Chronic; Calcinosis; Vascular Calcification; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Bone Density Conservation Agents; Membrane Transport Modulators; Micronutrients; Vitamins; Vasoconstrictor Agents; Calcium Channel Agonists; Vitamin D; Cholecalciferol; Calcitriol
• Other Study ID Numbers: AAAM7850

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No