End-Stage Renal Disease
Conditions
Keywords
Endstage renal disease, Vitamin D, Monocyte function
Brief summary
The goal of this study is to evaluate the role of nutritional Vitamin D deficiency as a potential contributor to the morbidity witnessed in patients with end-stage renal disease
Detailed description
The goals of this study are to elucidate the function of extrarenal 1 alpha-hydroxylase activity in the setting of renal failure and to evaluate the role of nutritional vitamin D deficiency as a potential contributor to monocyte-associated inflammatory pathways in patients with end-stage renal disease (ESRD). This study will consist of patients on chronic maintenance hemodialysis three times per week who have been identified to have nutritional vitamin D deficiency. After consent for study enrollment, patients will undergo a 4 week washout period of all active vitamin D supplementation. After washout is complete, an blood sample will be obtained for baseline 25(OH)D levels and monocyte isolation for analysis by flow cytometry. Patients will then be started on cholecalciferol 50,000 IU twice weekly for 8 weeks. 25-vitamin D levels will be monitored midway through the treatment phase of the study and dosing adjusted as further described in detail within the protocol section. An additional blood sample will be drawn post-therapy for repeat 25(OH)D levels and monocyte isolation for flow cytometry analysis.
Interventions
DRUGCholecalciferol
50,000 Units PO Twice weekly for 8 weeks
Sponsors
University of Kansas
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 88 Years
Healthy volunteers
No
Inclusion criteria
* End-stage renal disease undergoing maintenance hemodialysis at KUMC outpatient hemodialysis unit * Dialysis vintage of at least 6 months duration * Nutritional vitamin D deficiency, defined as 25(OH)D \<25 ng/ml * Age 21 to 88 years
Exclusion criteria
* Active infection * Recent hospitalization for acute illness (within last 1 month) * Refusal to study participation * Poorly controlled secondary hyperparathyroidism (iPTH\>500) * History of chronic inflammatory disease process, such as inflammatory bowel, rheumatoid arthritis, lupus, etc. * Cinacalcet therapy * Previous allergy to ergocalciferol * History of parathyroidectomy * Current treatment with immunosuppressant medications * Noncompliance with prescribed hemodialysis regimen (i.e. skipping treatments, ending sessions early) * Functional renal transplant within the last five years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Monocyte VDR Expression With Vitamin D Therapy | Change from End of Washout to Week 12 | Monocytes will be analyzed pre- and post-cholecalciferol by flow cytometry to measure changes in monocyte VDR expression. Unit of measure is represented by mean florescence intensity (MFI), which is a relative measure. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 50,000 U Vitamin D | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Washout (Weeks 1-4) | did not qualify after signing consent | 1 |
| Washout (Weeks 1-4) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cholecalciferol 50,000 U |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Monocyte Vitamin D receptor (VDR) expression | 572.7 MFI STANDARD_DEVIATION 172.3 |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Change in Monocyte VDR Expression With Vitamin D Therapy
Monocytes will be analyzed pre- and post-cholecalciferol by flow cytometry to measure changes in monocyte VDR expression. Unit of measure is represented by mean florescence intensity (MFI), which is a relative measure.
Time frame: Change from End of Washout to Week 12
Population: Clinical pilot trial - proof of concept
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol 50,000 U | Change in Monocyte VDR Expression With Vitamin D Therapy | 1899 units on a scale | Standard Deviation 644.4 |