Clearance of 25-hydroxyvitamin D in Cystic Fibrosis (CF)

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: d6-25-hydroxyvitamin D3

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single pharmacokinetics arm	Drug: d6-25-hydroxyvitamin D3; intravenous administration of stable isotope-labeled D6-25(OH)D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of D6-25(OH)D3	AUC is calculated using the linear trapezoidal method.	8 weeks
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.	8 weeks
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.	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic Formation Clearance of D6-25(OH)D3 Metabolites	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.	8 weeks
Serum Concentration of Calcium	Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3	7 days
Serum Concentration of Creatinine	Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3	7 days
Serum Concentration of AST	Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3	7 days
Serum Concentration of ALT	Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3	7 days

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Ian de Boer, MD, MS, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Actual): October 9, 2018
• Study Completion (Actual): September 6, 2023

Study Registration Dates

• First Submitted: February 17, 2017
• First Submitted That Met QC Criteria: April 6, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: cystic fibrosis; vitamin d catabolism
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcifediol; Hydroxycholecalciferols
• Other Study ID Numbers: 50852; R01DK099199 (U.S. NIH Grant/Contract); P30DK089507 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No