PK/PD of Vitamin D3 in Adults With CF

Sponsor

University of Southern California (Other)

Overall Status

Terminated

CT.gov ID

NCT03734744

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency Cystic Fibrosis	Dietary Supplement: Vitamin D3	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 17, 2019

Actual Primary Completion Date :

May 16, 2022

Actual Study Completion Date :

May 16, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adults with Cystic Fibrosis CF adults with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)	Dietary Supplement: Vitamin 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 Other Names: Cholecalciferol
Experimental: Non-CF Controls with Low vitamin D Non-CF controls with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)	Dietary Supplement: Vitamin 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 Other Names: Cholecalciferol

Arm

Intervention/Treatment

Experimental: Adults with Cystic Fibrosis

CF adults with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)

Dietary Supplement: Vitamin 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

Other Names:

Cholecalciferol

Experimental: Non-CF Controls with Low vitamin D

Non-CF controls with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)

Dietary Supplement: Vitamin 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

Other Names:

Cholecalciferol

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)