PK/PD of Vitamin D3 in Adults With CF

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Study Evaluating Single, High-dose Pharmacokinetics/Pharmacodynamics of Vitamin D3 in CF

Conditions
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Vitamin D Deficiency, Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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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)

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adults with Cystic Fibrosis<br>CF adults with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol) | Dietary Supplement: Vitamin D3<br>* 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<br>* Other names: Cholecalciferol;|
| Experimental: Non-CF Controls with Low vitamin D<br>Non-CF controls with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol) | Dietary Supplement: Vitamin D3<br>* 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<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of serum inflammatory biomarkers | Changes in IL-6, IL-8, TNF-α, IL-1β, C-reactive protein | 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Pharmacodynamics