Trial Outcomes & Findings for Bone Mass and Strength After Kidney Transplantation (NCT NCT02224144)

NCT ID: NCT02224144

Last Updated: 2025-03-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 61 participants
• Primary outcome timeframe: Baseline, 12 months
• Results posted on: 2025-03-07

Participant Flow

Participant milestones

Measure	Vitamin D3 Plus Calcitriol Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Overall Study STARTED	32	29
Overall Study COMPLETED	27	27
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Measure	Vitamin D3 Plus Calcitriol Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Overall Study Lost to Follow-up	3	1
Overall Study Death	2	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Bone Mass and Strength After Kidney Transplantation

Baseline characteristics by cohort

Measure	Vitamin D3 Plus Calcitriol n=32 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=29 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.	Total n=61 Participants Total of all reporting groups
Age, Continuous	51 years STANDARD_DEVIATION 14 • n=5 Participants	51 years STANDARD_DEVIATION 13 • n=7 Participants	51 years STANDARD_DEVIATION 13 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	28 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants	29 participants n=7 Participants	61 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Bone Density From Pre to Post-calcitriol Treatment Compared to Placebo as Assessed by Both Standard Methodologies	-0.81 percent change Standard Deviation 0.54	-0.70 percent change Standard Deviation 0.46

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Areal Bone Mass Density From Baseline to 12 Months After Transplantation BMD Ultradistal Radius	-3.19 percent change Standard Deviation 1.15	-3.30 percent change Standard Deviation 0.99
Percent Change in Areal Bone Mass Density From Baseline to 12 Months After Transplantation BMD Lumbar Spine	1.91 percent change Standard Deviation 0.94	0.85 percent change Standard Deviation 1.05
Percent Change in Areal Bone Mass Density From Baseline to 12 Months After Transplantation BMD Total Hip	0.88 percent change Standard Deviation 0.94	-0.09 percent change Standard Deviation 1.03
Percent Change in Areal Bone Mass Density From Baseline to 12 Months After Transplantation BMD Femoral Neck	0.64 percent change Standard Deviation 1.31	-0.45 percent change Standard Deviation 1.41

SECONDARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Failure Load Pre- and Post-transplantation Measured by High Resolution Imaging Methods Scan of radius	-5 percent change Standard Deviation 1	-3.4 percent change Standard Deviation 1.3
Percent Change in Failure Load Pre- and Post-transplantation Measured by High Resolution Imaging Methods Scan of tibia	-1.9 percent change Standard Deviation 1.2	-2.5 percent change Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change of Cortical Porosity Pre- and Post-intervention Scan of tibia	21 percent change Standard Deviation 7	13.3 percent change Standard Deviation 5.6
Percent Change of Cortical Porosity Pre- and Post-intervention Scan of radius	11.6 percent change Standard Deviation 11.1	12.5 percent change Standard Deviation 7.8

SECONDARY outcome

Timeframe: Baseline, 12 months

A semi-automated algorithm implemented in image processing language was used for assessment of lower leg arterial calcification (LLAC) and wrist arterial calcification (WAC).

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Vascular Calcifications Loads of the Lower Extremity LLAC	1.5 percent change Standard Deviation 3.5	-8.4 percent change Standard Deviation 6.1
Percent Change in Vascular Calcifications Loads of the Lower Extremity WAC	112 percent change Standard Deviation 118	68 percent change Standard Deviation 70

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Number of Patients With Vascular Calcifications of the Lower Extremity Baseline	13 Participants	9 Participants
Number of Patients With Vascular Calcifications of the Lower Extremity 12 months	13 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline, 12 months

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.

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Pre- and Post- Intervention Parathyroid Hormone (PTH) Levels	-63 percent change Standard Deviation 11	-59 percent change Standard Deviation 6

SECONDARY outcome

Timeframe: Baseline, 12 months

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).

Outcome measures

Measure	Vitamin D3 Plus Calcitriol n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=27 Participants Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment BSAP	9.6 percent change Standard Deviation 13.2	60 percent change Standard Deviation 35
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment Osteocalcin	-80 percent change Standard Deviation 4	-72 percent change Standard Deviation 6.2
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment P1NP	-14 percent change Standard Deviation 23	2.9 percent change Standard Deviation 17.7
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment CTX	-77 percent change Standard Deviation 5	-70 percent change Standard Deviation 6

Adverse Events

Vitamin D3 Plus Calcitriol

Serious events: 0 serious events

Other events: 12 other events

Deaths: 2 deaths

Vitamin D3 Plus Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vitamin D3 Plus Calcitriol n=32 participants at risk Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	Vitamin D3 Plus Placebo n=29 participants at risk Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.
Musculoskeletal and connective tissue disorders Hypercalcemia	37.5% 12/32 • 12 months	3.4% 1/29 • 12 months
Surgical and medical procedures Rejection	12.5% 4/32 • 12 months	27.6% 8/29 • 12 months
Musculoskeletal and connective tissue disorders Fracture after transplantation	0.00% 0/32 • 12 months	6.9% 2/29 • 12 months
General disorders Hospitalizations	28.1% 9/32 • 12 months	24.1% 7/29 • 12 months
Renal and urinary disorders Calcifications on Kidney Biopsy	21.9% 7/32 • 12 months	13.8% 4/29 • 12 months

Additional Information

Thomas Nickolas MD, MS

Columbia University

Phone: 2123053273

Email: tln2001@cumc.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place