Ergocalciferol Therapy in Calcidiol Deficient, Hemodialysis Patients on Therapeutic Doses of Paricalcitol
Status:
Completed
Trial end date:
2011-01-01
Target enrollment:
Participant gender:
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, the hypothesis is 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.
Interleulin-6 (IL-6) is thought to play a central role in insulin resistance by
down-regulating glucose transporter-4 messenger RNA. Furthermore, IL-6 levels are
significantly negatively associated with calcidiol levels, therefore will be measured as the
primary outcome.