Clearance of 25-hydroxyvitamin D in Cystic Fibrosis

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Single pharmacokinetics arm	d6-25-hydroxyvitamin D3	-

Primary Outcome Measures

Name	Time	Method
Metabolic Clearance of D6-25(OH)D3	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
AUC of D6-25(OH)D3	8 weeks	AUC is calculated using the linear trapezoidal method.
Terminal Half-life of D6-25(OH)D3	8 weeks	Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations.
Volume of Distribution of D6-25(OH)D3	8 weeks	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.