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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02224144

Enrollment

Registered

2014-08-25

Start date

2014-08-18

Completion date

2016-10-12

Last updated

2025-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

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

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.

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

DRUGVitamin D3

Vitamin D3 1000 IU per day for 12 months

DRUGCalcitriol

Calcitriol (Rocaltrol) 0.5 mcg per day for 12 months

DRUGPlacebo

Placebo (sugar pill) 1 pill per day for 12 months

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percent Change in Bone Density From Pre to Post-calcitriol Treatment Compared to Placebo as Assessed by Both Standard Methodologies	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

Measure	Time frame	Description
Percent Change in Failure Load Pre- and Post-transplantation Measured by High Resolution Imaging Methods	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.
Percent Change of Cortical Porosity Pre- and Post-intervention	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.
Percent Change in Vascular Calcifications Loads of the Lower Extremity	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).
Percent Change in Areal Bone Mass Density From Baseline to 12 Months After Transplantation	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 Pre- and Post- Intervention Parathyroid Hormone (PTH) Levels	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.
Percent Change in Pre- and Post- Intervention Levels of Bone Remodeling Markers for Bone Remodeling Assessment	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).
Number of Patients With Vascular Calcifications of the Lower Extremity	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Vitamin D3 Plus Calcitriol Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 0.5 mcg of Rocaltrol (calcitriol) daily for 12 months.	32
Vitamin D3 Plus Placebo Participants will take 1000 IU of Vitamin D3 (cholecalciferol) and 1 sugar pill (placebo) daily for 12 months.	29
Total	61

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	2	0
Overall Study	Lost to Follow-up	3	1
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Vitamin D3 Plus Calcitriol	Total	Vitamin D3 Plus Placebo
Age, Continuous	51 years STANDARD_DEVIATION 14	51 years STANDARD_DEVIATION 13	51 years STANDARD_DEVIATION 13
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	32 Participants	60 Participants	28 Participants
Region of Enrollment United States	32 participants	61 participants	29 participants
Sex: Female, Male Female	11 Participants	20 Participants	9 Participants
Sex: Female, Male Male	21 Participants	41 Participants	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 32	0 / 29
other Total, other adverse events	12 / 32	8 / 29
serious Total, serious adverse events	0 / 32	0 / 29

Outcome results

Primary

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.