Arterial Dysfunction, Chronic Kidney Disease
Conditions
Keywords
chronic kidney disease, vitamin D deficiency
Brief summary
The purpose of this study is to determine whether nutritional (cholecalciferol) or active vitamin D (calcitriol) supplementation improves vascular endothelial function in patients with stage IIIB and IV chronic kidney disease with vitamin D insufficiency or deficiency. The investigators hypothesize that the use of calcitriol supplementation will result in improved vascular endothelial function as compared to cholecalciferol supplementation.
Interventions
DRUGCholecalciferol
DRUGCalcitriol
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Chronic kidney disease stage IIIB or IV by 4 parameter Modified Diet in Renal Diseases Formula (Estimated Glomerular Filtration Rate \[GFR\] 44-15 ml/min/1.73m2) * Vitamin D (D2 + D3) deficient, defined as serum 25(OH)D level \< 30 ng/mL * Corrected serum calcium \< 10.2 mg/dL * Serum phosphate \< 4.6 mg/dL * Serum albumin \> 3.0 g/dL * Body mass index \< 40 kg/m2 * Ability to give informed consent
Exclusion criteria
* Significant co-morbid conditions that lead the investigator to conclude that life expectancy is less than 1 year * Expected to undergo living related kidney transplant in next 6 months * Pregnant, breastfeeding, or unwilling to use adequate birth control * History of severe liver disease * Nephrotic range proteinuria (\> 3.5 gm/day) * Use of active vitamin D analogs within 30 days of randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment. | 6 months | EDD will be measured by brachial artery flow-mediated dilation (FMD). The mean change in percent FMD from baseline will be documented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | 6 months | Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation |
| Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB | 6 months | The effect of calcitriol and cholecalciferol supplementation will be evaluated calculating the mean change in total vascular endothelial cell NFkB expression. NFkB expression is given as arbitrary units and represent ratios of endothelial cell protein expression to human umbilical vein endothelial cell (HUVEC) expression in order to account for any variation in the staining procedure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months
Cholecalciferol | 64 |
| Calcitriol Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months
Calcitriol | 64 |
| Total | 128 |
Baseline characteristics
| Characteristic | Cholecalciferol | Calcitriol | Total |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 13 | 59 years STANDARD_DEVIATION 12 | 58 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Hispanic | 16 Participants | 23 Participants | 39 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 18 Participants | 14 Participants | 32 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 23 Participants | 23 Participants | 46 Participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 42 Participants |
| Sex: Female, Male Male | 45 Participants | 41 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 64 | 0 / 64 |
| other Total, other adverse events | 1 / 64 | 4 / 64 |
| serious Total, serious adverse events | 9 / 64 | 5 / 64 |
Outcome results
Primary
Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment.
EDD will be measured by brachial artery flow-mediated dilation (FMD). The mean change in percent FMD from baseline will be documented.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment. | -0.5 percent change in FMD | Standard Deviation 4.2 |
| Calcitriol | Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment. | 0.3 percent change in FMD | Standard Deviation 3.5 |
Secondary
Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB
The effect of calcitriol and cholecalciferol supplementation will be evaluated calculating the mean change in total vascular endothelial cell NFkB expression. NFkB expression is given as arbitrary units and represent ratios of endothelial cell protein expression to human umbilical vein endothelial cell (HUVEC) expression in order to account for any variation in the staining procedure.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB | 0.03 ratio of NFkB to HUVEC expression | Standard Deviation 0.1 |
| Calcitriol | Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB | -0.01 ratio of NFkB to HUVEC expression | Standard Deviation 0.1 |
Secondary
Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein
Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation
Time frame: 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cholecalciferol | Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | End of Study | 3.1 mg/dL |
| Cholecalciferol | Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | Baseline | 3.0 mg/dL |
| Calcitriol | Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | Baseline | 3.4 mg/dL |
| Calcitriol | Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | End of Study | 3.9 mg/dL |