Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Study Overview
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Brief Summary
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The goal of this study is to better understand vitamin D catabolism and how it is affected by CKD and race.

Detailed Description
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Specifically, the study team will evaluate the metabolic clearance of 25-hydroxyvitamin D3 in individuals with varying degrees of CKD and among participants who self-report race as Caucasian, African American or African. The long-term goal of this work is to enhance the clinical evaluation and treatment of impaired vitamin D metabolism.

Official Title
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Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

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: Age ≥ 18 years Self-reported race Caucasian, African American, or African Serum total 25(OH)D 10-50 ng/mL Estimated GFR: 60 mL/min/1.73m2 (N=40) 15-45 mL/min/1.73m2 (N=40) <15 mL/min/1.73m2, treated with hemodialysis (N=40) 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) Use of vitamin D3, or vitamin D2 supplements exceeding a mean daily dose of 400 IU, within 3 months (wash-out allowed) 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 | 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 |
| --- | --- | --- |
| 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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of D6-25(OH)D3 | AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. | 8 weeks | 
| 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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. | 8 weeks | 
| 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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. | 8 weeks | 

 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