Chronic Kidney Disease (CKD), End-stage Renal Disease (ESRD)
Conditions
Brief summary
This investigation will consist of a prospective study utilizing two separate populations of patients with 25(OH)D deficiency, one population with chronic kidney disease (CKD) and one with normal renal function.
Detailed description
Vitamin D helps form and strengthens bones by allowing the body to absorb calcium. Vitamin D helps the immune system fight infection as well as helps keep muscles strong. Without enough vitamin D, bones can become weak, thin and brittle. Vitamin D is useful in people with all different types of health issues. CKD is the slow loss of kidney function over time. The main function of the kidneys is to remove wastes and excess water from the body. This loss of function usually takes months or years to occur Patients with CKD often have low levels of vitamin D in their blood. This study will have two groups of patients with CKD and one group of patients that have normal kidney function, but all groups will have low levels of vitamin D. The two groups with CKD (group 1 and group 2) will receive either cholecalciferol or calcitriol. The purpose of having a control group (group 3) without CKD will be to evaluate if any changes that are witnessed in response to vitamin D therapy are specific to patients with kidney disease or apply to all patients with vitamin D deficiency who receive vitamin D supplements. There are two different drugs in this study. One is called Calcitriol and is approved by the Food and Drug Administration (FDA) as a vitamin D supplement. The other drug is called cholecalciferol and it is approved by the FDA. Unlike calcitriol, cholecalciferol is a nutritional form of vitamin D that can often be found in various types of foods and its chemical structure must be changed by the body to become the active form of vitamin D. It is believed that cholecalciferol may have different effects in the body compared to calcitriol. It is possible that CKD patients would benefit from receiving both of these drugs, but this is currently unclear. While on this study you will receive either one of these study drugs, depending on which group you are assigned to.
Interventions
DRUGCholecalciferol - CKD
Cholecalciferol tablet 50,000 IU twice weekly for 8 weeks
DEVICECalcitriol - CKD
Calcitriol 0.25 mcg once daily for 8 weeks
DRUGCholecalciferol - non-CKD
Cholecalciferol tablet 50,000 IU twice weekly for 8 weeks
Sponsors
University of Kansas Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Chronic kidney disease w/GFR\<35ml/min * Nutritional vitamin D deficiency, defined as 25(OH)D \< 25ng/ml * Secondary hyperparathyroidism, PTH\>75pg/mL
Exclusion criteria
* Active infection * Recent hospitalization for acute illness (within last month) * Refusal to study participation * History of chronic inflammatory disease process (i.e. inflammatory bowel, rheumatoid arthritis, SLE, etc.) * Allergy to cholecalciferol or calcitriol * History of parathyroidectomy * Functional renal transplant within 5 years * Current treatment with immunosuppressant medications * Noncompliance with prescribed medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monocyte Protein Expression | 8 weeks of therapy | Flow cytometry analysis of monocyte CD14, ACE, VDR, and Mac-1 expression |
| Change in 24,25(OH)2D Levels in CKD vs. Non-CKD Subjects Receiving Cholecalciferol | 8 weeks of therapy | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Cholecalciferol Patients in this group have low vitamin D levels and Chronic Kidney Disease (CKD). Patients will be randomized to group 1 or group 2.
Cholecalciferol: Cholecalciferol tablet, 50,000 units twice a week | 15 |
| Group 2: Calcitriol Patients in this group have low vitamin D levels and Chronic Kidney Disease (CKD). Patients will be randomized to group 1 or group 2.
calcitriol: calcitriol 0.25 mcg every day | 17 |
| Group 3: Cholecalciferol Patients in this arm have low vitamin D levels and normal kidney function. They will be put into group 3.
Cholecalciferol: Cholecalciferol tablet, 50,000 units twice a week | 24 |
| Total | 56 |
Baseline characteristics
| Characteristic | Group 2: Calcitriol | Group 3: Cholecalciferol | Group 1: Cholecalciferol | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 6 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 20 Participants | 9 Participants | 40 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.6 | 48.5 years STANDARD_DEVIATION 14.2 | 60.1 years STANDARD_DEVIATION 13.3 | 56.1 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 17 participants | 24 participants | 15 participants | 56 participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 9 Participants | 40 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 1 / 17 | 1 / 24 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 | 0 / 24 |
Outcome results
Primary
Change in 24,25(OH)2D Levels in CKD vs. Non-CKD Subjects Receiving Cholecalciferol
Time frame: 8 weeks of therapy
Population: The primary comparison for this outcome of interest was between subjects taking cholecalciferol, so the calcitriol group (group 2) was excluded from the analysis. Only 15 patients per group had data analyzed for this outcome of interest; thus, the number analyzed per group differs from the enrolled numbers.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Cholecalciferol - CKD | Change in 24,25(OH)2D Levels in CKD vs. Non-CKD Subjects Receiving Cholecalciferol | 1.59 ng/ml | Standard Deviation 0.73 |
| Group 2: Calcitriol - CKD | Change in 24,25(OH)2D Levels in CKD vs. Non-CKD Subjects Receiving Cholecalciferol | 3.59 ng/ml | Standard Deviation 1.14 |
Primary
Monocyte Protein Expression
Flow cytometry analysis of monocyte CD14, ACE, VDR, and Mac-1 expression
Time frame: 8 weeks of therapy
Population: The primary comparison for this outcome was between only CKD groups (groups 1 and 2); therefore data from the non-CKD group (group 3) was not analyzed for this outcome. Only 15 patients per group had data analyzed for this outcome of interest; thus, the number analyzed per group differs from the enrolled numbers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group 1: Cholecalciferol - CKD | Monocyte Protein Expression | CD14 | 34110 relative fluorescence units | Standard Deviation 9372 |
| Group 1: Cholecalciferol - CKD | Monocyte Protein Expression | ACE | 1359 relative fluorescence units | Standard Deviation 347.2 |
| Group 1: Cholecalciferol - CKD | Monocyte Protein Expression | VDR | 2799 relative fluorescence units | Standard Deviation 1210 |
| Group 1: Cholecalciferol - CKD | Monocyte Protein Expression | Mac-1 | 14318 relative fluorescence units | Standard Deviation 4196.4 |
| Group 2: Calcitriol - CKD | Monocyte Protein Expression | Mac-1 | 14278.5 relative fluorescence units | Standard Deviation 4891.3 |
| Group 2: Calcitriol - CKD | Monocyte Protein Expression | CD14 | 38540 relative fluorescence units | Standard Deviation 16880 |
| Group 2: Calcitriol - CKD | Monocyte Protein Expression | VDR | 3468 relative fluorescence units | Standard Deviation 3123 |
| Group 2: Calcitriol - CKD | Monocyte Protein Expression | ACE | 1360 relative fluorescence units | Standard Deviation 290.8 |