Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: D6-25-hydroxyvitamin D3


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Population<br>D6-25-hydroxyvitamin D3 with vitamin D3 | Drug: D6-25-hydroxyvitamin D3<br>* Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3<br>* Other names: stable isotope deuterium-labeled 25(OH)D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Baseline, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, vitamin d catabolism