An interventional study of Cholecalciferol in Chronic Kidney Diseases and Deficiency, Vitamin D, sponsored by University of Colorado, Denver. Completed at 2 sites in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-30.
Sponsored by University of Colorado, Denver · Not applicable, Interventional, and Other
This study investigates the effect of vitamin D deficiency on drug metabolism and transport in patients with chronic kidney disease (CKD) and in healthy controls.
The central hypothesis is that vitamin D concentrations independently affect metabolism and transport function in CKD patients. An over-arching goal of this proposal is to make drug therapies safer and more effective to reduce the significant morbidity and mortality in patients with CKD.
Specific Aim 1: Determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will mechanistically evaluate the function of major pathways of metabolism and transport by prospectively studying clearance phenotypes utilizing "probe" drugs commonly used for this purpose in CKD patients and healthy volunteers under vitamin D deficient and replete states. Bupropion, midazolam, olmesartan, fexofenadine, in addition to an endogenous probe (N-methylnicotinamide), will be used to phenotype major phase I drug metabolizing enzymes [cytochrome P450 2B6 (CYP2B6), cytochrome P450 3A4/5 (CYP3A4/5)], and transporters [multidrug resistance associated protein 2 (MRP2), P-glycoprotein (P-gp), and multidrug and toxin extrusion protein 1/2K (MATE1/2K)], respectively. Hypothesis: The in vivo function of individual pathways of xenobiotic metabolism and transport are affected by vitamin D status (and CKD).
Specific Aim 2: Determine the effect of CKD on the in vivo function of individual CYPs responsible for vitamin D metabolism and the pharmacokinetics of cholecalciferol (vitamin D3). The research will prospectively measure the activity of CYP450s responsible for cholecalciferol metabolism, and simultaneously evaluate the pharmacokinetics (PK) of cholecalciferol after single- and multiple-dose administration to CKD patients (stages 1-5) and healthy volunteers. Hypothesis: CKD alters the activity of individual CYPs responsible for vitamin D metabolism, leading to modified clearance of cholecalciferol.
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This study's enrollment of 23 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.
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Inclusion criteria for CKD patients:
Inclusion Criteria for Healthy Controls:
Exclusion criteria for CKD patients:
Exclusion Criteria for Healthy Controls:
The aim of Arm 1 is to determine the effect of vitamin D deficiency and repletion on xenobiotic clearance in vivo. The study will evaluate the in vivo function of targeted metabolism and transport pathways in 40 CKD and 18 healthy volunteer subjects (controls) under the influence of a vitamin D depleted state and repeated under a vitamin D replete state with cholecalciferol. The function of two major phase I drug metabolizing enzymes (CYP2B6, CYP3A), and three transporters \[P-gp, MRP2, and MATE1/2K\] will be assessed by administering oral bupropion, midazolam, olmesartan, and fexofenadine.
Dietary Supplement: Cholecalciferol
The aim of Arm 2 is to determine the effect of CKD on the in vivo function of individual CYP450s responsible for vitamin D metabolism and their functional relevance on the pharmacokinetics of cholecalciferol. A total of 90 CKD subjects will be enrolled \[30 per group: group I (CKD stage 1/2), group II (CKD stage 3), and group III (CKD stage 4/5, pre-ESRD)\], as well as 30 healthy controls.
Dietary Supplement: Cholecalciferol
Vitamin D deficient patients, in both Arms, will be administered Cholecalciferol 5,000 IU daily.
Also known as: Vitamin D
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan and fexofenadine) from baseline to 12 weeks.
Change in area under the plasma concentration time curves for probe drugs (bupropion, midazolam, olmesartan, and fexofenadine) at 12 weeks.
Time frame: 12 weeks
Change in area under the plasma concentration time curves for cholecalciferol from baseline to 12 weeks.
Change in area under the plasma concentration time curves for cholecalciferol at 12 weeks.
Time frame: 12 weeks
Plan to share: No
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This study is completed, as verified in Jun 2021. You cannot join it, but the record below documents what was studied.
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University of Colorado, Denver