Cystic Fibrosis, Vitamin D Deficiency
Conditions
Keywords
Pharmacokinetics, Pharmacodynamics
Brief summary
Despite the extensive literature on adverse clinical outcomes associated with vitamin D deficiency, there are currently no proven treatment strategy that effectively achieves and maintains optimal serum vitamin D status in cystic fibrosis (CF) patients. For the treatment of vitamin D deficiency, CF Foundation currently recommends 2,000 IU daily. However, because achieving adequate serum 25(OH)D levels is a challenge in CF, higher doses of vitamin D may be necessary to reach and maintain vitamin D sufficiency. Poor oral bioavailability of ergocalciferol has been demonstrated in CF patients, which may potentially also be an issue with cholecalciferol. In order to optimize the treatment of vitamin D deficiency in CF, the kinetic disposition must be well understood. However, there are very few data currently available describing the kinetics of both vitamin D and 25-hydroxyvitamin D, and to the investigator's knowledge, no studies have yet characterized the pharmacokinetic disposition of vitamin D and its metabolites in cystic fibrosis. Addressing this issue is crucial in effectively and safely correcting vitamin D deficiency in CF.
Detailed description
Clinically stable CF patients with a history of pancreatic insufficiency (n=6) and matching non-CF subjects (n=6) will be recruited in this study. All subjects will be pre-screened for 25(OH)D status to include those with 25(OH)D levels below 30 ng/mL. The subjects will receive a single oral dose (300,000 - 600,000 IU) of vitamin D3, and the dose will be based on study participant's baseline 25-hydroxyvitamin D3 level. For CF patients, the dose will be administered with food and pancreatic enzyme supplement. This dose was chosen as previous studies in pediatric CF patients demonstrated that a large single dose of up to 600,000 IU vitamin D3 raised and maintained sufficient 25(OH)D concentrations without any signs of adverse events.
Interventions
DIETARY_SUPPLEMENTVitamin D3
Vitamin D is a fat-soluble vitamin that plays an important role in immune modulation in addition to its classical roles in regulation of calcium homeostasis and bone health
Sponsors
University of Southern California
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For CF, diagnosis of CF based on positive sweat chloride or known CF mutation * For CF, Patients with pancreatic insufficiency * Age ≥ 18 years * Serum 25(OH)D concentrations below 30 ng/mL (75 nmol/L)
Exclusion criteria
* Pregnancy * History of lung transplant, * Severe anemia (hemoglobin concentration \< 7 g/dL), * Liver disease (AST/ALT \> 3x ULN), kidney disease (GFR ≤ 40 mL/min), or granulomatous conditions * Patients taking steroids, cholesterol-lowering drug (cholestyramine), weight-loss drugs (orlistat) , statins, anti-tuberculosis drugs (rifampin and isoniazid), phenobarbital, phenytoin, carbamazepine, immunosuppressants (cyclosporine, tacrolimus)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peak plasma concentrations (Cmax) | 10 weeks |
| Time taken to reach the maximum concentration (Tmax) | 10 weeks |
| Area under the plasma concentration versus time curve (AUC) | 10 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of serum inflammatory biomarkers | 10 weeks | Changes in IL-6, IL-8, TNF-α, IL-1β, C-reactive protein |
Countries
United States
Outcome results
None listed