CF: Clearance of 25-hydroxyvitamin D in Cystic Fibrosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single pharmacokinetics arm
|
Drug: d6-25-hydroxyvitamin D3
intravenous administration of stable isotope-labeled D6-25(OH)D3
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
Other Outcome Measures
- Metabolic formation clearance of D6-25(OH)D3 metabolites [8 weeks]
Metabolic formation clearance is calculated as the daughter metabolite plasma AUC divided by the AUC of D6-25(OH)D3 (metabolite/parent AUC ratio). AUC is calculated using the linear trapezoidal method.
- serum concentration of calcium [7 days]
Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3
- serum concentration of creatinine [7 days]
Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3
- serum concentration of AST [7 days]
Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3
- serum concentration of ALT [7 days]
Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3
Eligibility Criteria
Criteria
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:
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Primary hyperparathyroidism
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Gastric bypass
-
Tuberculosis or sarcoidosis
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Current pregnancy
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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)
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History of kidney transplantation or end stage renal disease treated with dialysis
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Use of vitamin D3 or vitamin D2 supplements exceeding a mean daily dose of 400 IU, within 3 months (wash-out allowed)
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Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
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Serum calcium > 10.1 mg/dL
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Hemoglobin < 9 g/dL
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Washington | Seattle | Washington | United States | 98104 |
Sponsors and Collaborators
- University of Washington
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
- Principal Investigator: Ian de Boer, MD, MS, University of Washington
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 50852
- R01DK099199
- P30DK089507