Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

University of Washington19 enrolled

Overview

The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.

We expect that this study will enhance interpretation of available diagnostic tests, inform the results of ongoing large clinical trials of vitamin D supplements, and help develop new strategies to target vitamin D to improve health.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Chronic Kidney Disease

Interventions

D6-25-hydroxyvitamin D3DRUG

Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Successful prior completion of related protocol CLEAR (NCT02937350) or CLEAR-CF (NCT03104855) * Age ≥ 18 years * Self-reported race Caucasian, African American, or African Exclusion Criteria: * Primary hyperparathyroidism * Gastric bypass * Tuberculosis or sarcoidosis * Current pregnancy * Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin \>=2 mg/dL, serum albumin \<=3.5 g/dL, or PT \>= 4 seconds) * History of kidney transplantation (unless failed transplant now treated with hemodialysis) * Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed) * Serum calcium \> 10.1 mg/dL * Hemoglobin \< 10 g/dL

Locations (1)

University of Washington

Seattle, Washington, United States

Outcomes

Primary Outcomes

Change in Metabolic Clearance of D6-25(OH)D3

Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Time frame: Baseline, 6 months

Secondary Outcomes

Change in AUC of D6-25(OH)D3

AUC is calculated using the linear trapezoidal method. Change in the AUC of D6-25(OH)D3 will be calculated as D6-25(OH)D3 AUC measured during CLEAR-PLUS minus D6-25(OH)D3 AUC previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Time frame: Baseline, 6 months

Change in Terminal Half-life of D6-25(OH)D3

Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations. Change in the terminal half-life of D6-25(OH)D3 will be calculated as D6-25(OH)D3 half-life measured during CLEAR-PLUS minus D6-25(OH)D3 half-life previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Time frame: Baseline, 6 months

Change in Volume of Distribution of D6-25(OH)D3

Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma. Change in the volume of distribution of D6-25(OH)D3 will be calculated as D6-25(OH)D3 volume of distribution measured during CLEAR-PLUS minus D6-25(OH)D3 volume of distribution previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.

Data from ClinicalTrials.gov

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