Clearance of 25-hydroxyvitamin D in Cystic Fibrosis

Study Overview
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Brief Summary
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The goal of this study is to define 25(OH)D3 catabolism in CF patients using gold standard pharmacokinetics studies. Specifically, the investigators will evaluate the metabolic clearance of 25(OH)D3 among participants with CF and matched control subjects. The goal of this work is to provide the first comprehensive characterization of vitamin D metabolism in CF patients and promote novel hypotheses for subsequent studies.

Official Title
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Clearance of 25-hydroxyvitamin D in Cystic Fibrosis

Conditions
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Cystic Fibrosis

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 Serum total 25(OH)D 10-50 ng/mL Diagnosis of cystic fibrosis in accordance with CF Foundation Guidelines; OR, normal CONTROL 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 or end stage renal disease treated with dialysis 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 < 9 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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Accepts Healthy Volunteers

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: Single pharmacokinetics arm<br> | Drug: d6-25-hydroxyvitamin D3<br>* intravenous administration of stable isotope-labeled D6-25(OH)D3<br>|

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. | 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. | 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. | 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. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, vitamin d catabolism