Ergocalciferol Therapy in Calcidiol Deficient, Hemodialysis Patients on Therapeutic Doses of Paricalcitol
Information source: University of Utah
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Inflammation; Insulin Resistance
Intervention: ergocalciferol 50,000 U/ week (Drug)
Phase: N/A
Status: Completed
Sponsored by: University of Utah Official(s) and/or principal investigator(s): Srinivasan Beddhu, MD, Principal Investigator, Affiliation: University of Utah Vidya Raj Krishnamurthy, MD, Principal Investigator, Affiliation: University of Utah
Summary
The objective of this study is to determine the effects of cholecalciferol treatment on
inflammation and insulin resistance, in patients on hemodialysis that are previously treated
with paricalcitol.
Cholecalciferol is produced by the action of sunlight on a cholesterol precursor in the
skin. This compound is then converted to calcidiol (25(OH) D3) in the liver, whereupon
calcidiol is converted in the kidney to calcitriol (1,25(OH)2D3), the active form of vitamin
D. However, recently it has been shown that deficiency of either calcidiol or calcitriol is
associated with inflammation, insulin resistance and increased mortality in the general
population. Furthermore, when both calcidiol and calcitriol were deficient, the mortality
risk was much higher than the deficiency of either alone. A possible explanation is that
some of the non-renal tissues might critically depend on the endogenous conversion of
calcidiol to calcitriol and not on circulating levels of calcitriol. Thus, low circulating
levels of calcidiol might be associated with tissue level functional calcitriol deficiency
despite adequate circulating levels of calcitriol.
Therefore, we hypothesize that:
1. In non-diabetic hemodialysis (HD) patients treated with therapeutic doses of
paricalcitol (an analog of calcitriol), calcidiol deficiency is associated with
inflammation and insulin resistance and
2. In calcidiol deficient, non-diabetic HD patients with inflammation and treated with
therapeutic doses of paricalcitol, cholecalciferol will reverse the calcidiol
deficiency and thereby, reduce inflammation and insulin resistance.
Clinical Details
Official title: Ergocalciferol Therapy in Calcidiol Deficient, Hemodialysis Patients on Therapeutic Doses of Paricalcitol
Study design: Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Inflammation, Inuslin resistance, paricalcitol
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Non-diabetic in-center HD patients on stable doses of paricalcitol over past three months
with intact parathyroid hormone (iPTH) in the therapeutic range (150-300 pg/ml) will be
identified from review of the dialysis program electronic medical records. Woman in the
reproductive age group (ages 18-55), excluding those women who have undergone
hysterectomy, oopherectomy will undergo a serum β-HCG levels during the selection process.
If β-HCG levels are positive these patients will be excluded from the study.
Inclusion criteria:
- Non diabetic patients on HD, on stable dose of paricalcitol supplements for at least
3 months with iPTH in target range. Of the 60 patients enrolled in the observational
component, those with high CRP (> 3 mg/dl) and calcidiol deficiency (< 15 ng/ml) will
be eligible to participate in the interventional study.
- As the median CRP in the HEMO Study was 11 mg/L and > 80% of HD patients are
calcidiol deficient [10], most of the screened patients will be eligible. In each
year, the first 12 patients who meet the above criteria and consent for the
interventional component, a randomized cross-over trial of cholecalciferol 50,000 IU/
week vs. matching placebo will be conducted.
Exclusion criteria:
- Diabetic patients, not on paricalcitol, enrolled in other interventional studies,
hospitalized in the past month or treated for an infection in the past month and
pregnancy.
- We will conduct a pregnancy test for women in the reproductive age group (18-55
years) during the initial screening process. We will obtain serum β-HCG levels to
rule out pregnancy and the test will be paid for by the study. The results will be
reviewed by the PI. If β-HCG levels are positive these patients will be withdrawn
from the study.
Locations and Contacts
University of Utah, Salt Lake City, Utah 84112, United States
Additional Information
Starting date: May 2009
Last updated: December 12, 2013
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