Clearance of 25-hydroxyvitamin D in Cystic Fibrosis (CF)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
d6-25-hydroxyvitamin D3
Sponsored by
About this trial
This is an interventional diagnostic trial for Cystic Fibrosis focused on measuring cystic fibrosis, vitamin d catabolism
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Serum total 25(OH)D 10-50 ng/mL
- Diagnosis of cystic fibrosis in accordance with CF Foundation Guidelines; OR, normal CONTROL
Exclusion Criteria:
- Primary hyperparathyroidism
- Gastric bypass
- Tuberculosis or sarcoidosis
- Current pregnancy
- Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)
- History of kidney transplantation or end stage renal disease treated with dialysis
- Use of vitamin D3 or vitamin D2 supplements exceeding a mean daily dose of 400 IU, within 3 months (wash-out allowed)
- Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
- Serum calcium > 10.1 mg/dL
- Hemoglobin < 9 g/dL
Sites / Locations
- University of Washington
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single pharmacokinetics arm
Arm Description
Outcomes
Primary Outcome Measures
Metabolic Clearance of D6-25(OH)D3
Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method.
Secondary Outcome Measures
AUC of D6-25(OH)D3
AUC is calculated using the linear trapezoidal method.
Terminal Half-life of D6-25(OH)D3
Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations.
Volume of Distribution of D6-25(OH)D3
Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma.
Full Information
NCT ID
NCT03104855
First Posted
February 17, 2017
Last Updated
September 18, 2023
Sponsor
University of Washington
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT03104855
Brief Title
Clearance of 25-hydroxyvitamin D in Cystic Fibrosis
Acronym
CF
Official Title
Clearance of 25-hydroxyvitamin D in Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
April 3, 2017 (Actual)
Primary Completion Date
October 9, 2018 (Actual)
Study Completion Date
September 6, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of this study is to define 25(OH)D3 catabolism in CF patients using gold standard pharmacokinetics studies. Specifically, the investigators will evaluate the metabolic clearance of 25(OH)D3 among participants with CF and matched control subjects. The goal of this work is to provide the first comprehensive characterization of vitamin D metabolism in CF patients and promote novel hypotheses for subsequent studies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
cystic fibrosis, vitamin d catabolism
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single pharmacokinetics arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
d6-25-hydroxyvitamin D3
Intervention Description
intravenous administration of stable isotope-labeled D6-25(OH)D3
Primary Outcome Measure Information:
Title
Metabolic Clearance of D6-25(OH)D3
Description
Metabolic clearance is calculated as the administered dose of 25(OH)D3 divided by the area under the plasma concentration-time curve (AUC). AUC is calculated using the linear trapezoidal method.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
AUC of D6-25(OH)D3
Description
AUC is calculated using the linear trapezoidal method.
Time Frame
8 weeks
Title
Terminal Half-life of D6-25(OH)D3
Description
Terminal half-life is equal to ln2/k, where k is the slope of the terminal regression line estimated using ≥3 plasma concentrations.
Time Frame
8 weeks
Title
Volume of Distribution of D6-25(OH)D3
Description
Volume of distribution in the central compartment is calculated as dose/C0, where dose is the administered dose of 25(OH)D3 and C0 is the initial (estimated) concentration of drug in plasma.
Time Frame
8 weeks
Other Pre-specified Outcome Measures:
Title
Metabolic Formation Clearance of D6-25(OH)D3 Metabolites
Description
Metabolic formation clearance is calculated as the daughter metabolite plasma AUC divided by the AUC of D6-25(OH)D3 (metabolite/parent AUC ratio). AUC is calculated using the linear trapezoidal method.
Time Frame
8 weeks
Title
Serum Concentration of Calcium
Description
Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3
Time Frame
7 days
Title
Serum Concentration of Creatinine
Description
Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3
Time Frame
7 days
Title
Serum Concentration of AST
Description
Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3
Time Frame
7 days
Title
Serum Concentration of ALT
Description
Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3
Time Frame
7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Serum total 25(OH)D 10-50 ng/mL
Diagnosis of cystic fibrosis in accordance with CF Foundation Guidelines; OR, normal CONTROL
Exclusion Criteria:
Primary hyperparathyroidism
Gastric bypass
Tuberculosis or sarcoidosis
Current pregnancy
Child-Pugh Class B or C cirrhosis (i.e. cirrhosis with ascites, hepatic encephalopathy, bilirubin >=2 mg/dL, serum albumin <=3.5 g/dL, or PT >= 4 seconds)
History of kidney transplantation or end stage renal disease treated with dialysis
Use of vitamin D3 or vitamin D2 supplements exceeding a mean daily dose of 400 IU, within 3 months (wash-out allowed)
Use of 1,25(OH)2D3 or an analogue, calcimimetics, or medications known to induce CYP24A1 within 4 weeks (wash-out allowed)
Serum calcium > 10.1 mg/dL
Hemoglobin < 9 g/dL
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian de Boer, MD, MS
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
Learn more about this trial
Clearance of 25-hydroxyvitamin D in Cystic Fibrosis
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