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PK/PD of Vitamin D3 in Adults With CF

Primary Purpose

Vitamin D Deficiency, Cystic Fibrosis

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Vitamin D Deficiency focused on measuring Pharmacokinetics, Pharmacodynamics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Keck Hospital of University of Southern California

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Adults with Cystic Fibrosis

Non-CF Controls with Low vitamin D

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
November 6, 2018
Last Updated
May 16, 2022
Sponsor
University of Southern California
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1. Study Identification

Unique Protocol Identification Number
NCT03734744
Brief Title
PK/PD of Vitamin D3 in Adults With CF
Official Title
A Pilot Study Evaluating Single, High-dose Pharmacokinetics/Pharmacodynamics of Vitamin D3 in CF
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Clinical research currently on hold
Study Start Date
June 17, 2019 (Actual)
Primary Completion Date
May 16, 2022 (Actual)
Study Completion Date
May 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Southern California

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vitamin D Deficiency, Cystic Fibrosis
Keywords
Pharmacokinetics, Pharmacodynamics

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adults with Cystic Fibrosis
Arm Type
Experimental
Arm Description
CF adults with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)
Arm Title
Non-CF Controls with Low vitamin D
Arm Type
Experimental
Arm Description
Non-CF controls with vitamin D insufficiency or deficiency will receive 300,000-600,000 IU vitamin D3 (cholecalciferol)
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Cholecalciferol
Intervention Description
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
Primary Outcome Measure Information:
Title
Peak plasma concentrations (Cmax)
Time Frame
10 weeks
Title
Time taken to reach the maximum concentration (Tmax)
Time Frame
10 weeks
Title
Area under the plasma concentration versus time curve (AUC)
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Levels of serum inflammatory biomarkers
Description
Changes in IL-6, IL-8, TNF-α, IL-1β, C-reactive protein
Time Frame
10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul M Beringer, Pharm.D.
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
Keck Hospital of University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21193656
Citation
Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011 Jan;86(1):50-60. doi: 10.4065/mcp.2010.0567.
Results Reference
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PubMed Identifier
22399505
Citation
Tangpricha V, Kelly A, Stephenson A, Maguiness K, Enders J, Robinson KA, Marshall BC, Borowitz D; Cystic Fibrosis Foundation Vitamin D Evidence-Based Review Committee. An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation. J Clin Endocrinol Metab. 2012 Apr;97(4):1082-93. doi: 10.1210/jc.2011-3050. Epub 2012 Mar 7.
Results Reference
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PubMed Identifier
22998937
Citation
Shepherd D, Belessis Y, Katz T, Morton J, Field P, Jaffe A. Single high-dose oral vitamin D3 (stoss) therapy--a solution to vitamin D deficiency in children with cystic fibrosis? J Cyst Fibros. 2013 Mar;12(2):177-82. doi: 10.1016/j.jcf.2012.08.007. Epub 2012 Sep 19.
Results Reference
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PubMed Identifier
22928076
Citation
Grossmann RE, Zughaier SM, Kumari M, Seydafkan S, Lyles RH, Liu S, Sueblinvong V, Schechter MS, Stecenko AA, Ziegler TR, Tangpricha V. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. Dermatoendocrinol. 2012 Apr 1;4(2):191-7. doi: 10.4161/derm.20332.
Results Reference
background
PubMed Identifier
11237938
Citation
Lark RK, Lester GE, Ontjes DA, Blackwood AD, Hollis BW, Hensler MM, Aris RM. Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr. 2001 Mar;73(3):602-6. doi: 10.1093/ajcn/73.3.602.
Results Reference
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PK/PD of Vitamin D3 in Adults With CF

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