Bone Mass and Strength After Kidney Transplantation

• ClinicalTrials.gov Identifier: NCT02224144
• Recruitment Status: Completed
• First Posted: August 25, 2014
• Last Update Posted: April 15, 2022
• Sponsor: Columbia University
• Collaborator: Satellite Healthcare
• Information provided by (Responsible Party): Thomas Nickolas, MD MS, Columbia University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
End Stage Renal Disease; Kidney Transplantation; Bone Loss; Fractures; Vascular Calcifications	Drug: Vitamin D3; Drug: Calcitriol; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Comparative Trial of Calcitriol Versus Placebo for the Preservation of Bone Mass and Strength After Kidney Transplantation
• Actual Study Start Date: August 18, 2014
• Actual Primary Completion Date: October 12, 2016
• Actual Study Completion Date: October 12, 2016

Arms and Interventions

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 Name: cholecalciferol; Drug: Calcitriol; Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months; Other Name: 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 Name: cholecalciferol; Drug: Placebo; Placebo (sugar pill) 1 pill per day for 12 months

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.

   .

7. 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

Columbia University Irving Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Satellite Healthcare

Investigators

• Principal Investigator: Thomas Nickolas, MD, MS; Columbia University

More Information

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.

• Responsible Party: Thomas Nickolas, MD MS, Associate Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT02224144
• Other Study ID Numbers: AAAM7850
• First Posted: August 25, 2014
• Last Update Posted: April 15, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Keywords provided by Thomas Nickolas, MD MS, Columbia University:

Kidney Transplantation; Calcitriol; Bone Mineral Density; Bone Mass and Strength; Vascular Calcifications; Hyperparathyroidism; Parathyroid Hormone

Additional relevant MeSH terms:

Kidney Failure, Chronic; Calcinosis; Vascular Calcification; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Calcium Metabolism Disorders; Metabolic Diseases; Vitamin D; Cholecalciferol; Calcitriol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents