PK/PD of Vitamin D3 in Adults With CF

Not Applicable

Terminated

• Conditions: Vitamin D Deficiency; Cystic Fibrosis
• Interventions: Dietary Supplement: Vitamin D3

• Registration Number: NCT03734744
• Lead Sponsor: University of Southern California

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-11-06
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-08
• Study Start: 2019-06-17
• Status Verified: 2022-05
• Primary Completion: 2022-05-16
• Study Completion: 2022-05-16
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non-CF Controls with Low vitamin D	Vitamin D3	Non-CF controls with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)
Adults with Cystic Fibrosis	Vitamin D3	CF adults with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve (AUC)	10 weeks
Peak plasma concentrations (Cmax)	10 weeks
Time taken to reach the maximum concentration (Tmax)	10 weeks

Secondary Outcome Measures

Name	Time	Method
Levels of serum inflammatory biomarkers	10 weeks	Changes in IL-6, IL-8, TNF-α, IL-1β, C-reactive protein

Trial Locations

Locations (1)

Keck Hospital of University of Southern California; 🇺🇸 Los Angeles, California, United States