Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Chronic Kidney Disease Clinical Trial

— CLEAR-PLUS  

Official title:

Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03576716
• Other study ID #: STUDY00000608
• Secondary ID: R01DK099199
• Status: Completed
• Phase: Phase 1
• Start date: June 1, 2018
• Est. completion date: January 1, 2021

Study information

• Verified date: May 2022
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.

Description:

We expect that this study will enhance interpretation of available diagnostic tests, inform the results of ongoing large clinical trials of vitamin D supplements, and help develop new strategies to target vitamin D to improve health.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 1, 2021
• Est. primary completion date: July 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Successful prior completion of related protocol CLEAR (NCT02937350) or CLEAR-CF (NCT03104855)

• Age = 18 years

• Self-reported race Caucasian, African American, or African

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 (unless failed transplant now treated with hemodialysis)

• 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 < 10 g/dL

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• D6-25-hydroxyvitamin D3
Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in 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. Changes in the metabolic formation clearance of D6-25(OH)D3 metabolites will be calculated as metabolic formation clearance measured during CLEAR-PLUS minus metabolic formation clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.	Baseline, 6 months
Other	Change in the Serum Concentration of Calcium	Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3 administration. The change listed is between two timepoints.	Baseline, 7 days
Other	Change in the Serum Concentration of Creatinine	Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3 administration. The change listed is between two timepoints.	Baseline, 7 days
Other	Change in the Serum Concentration of AST	Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3 administration. The change listed is between two timepoints.	Baseline, 7 days
Other	Change in the Serum Concentration of ALT	Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3 administration. The change listed is between two timepoints.	Baseline, 7 days
Primary	Change in 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. Change in clearance of D6-25(OH)D3 will be calculated as D6-25(OH)D3 clearance measured during CLEAR-PLUS minus D6-25(OH)D3 clearance previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.	Baseline, 6 months
Secondary	Change in AUC of D6-25(OH)D3	AUC is calculated using the linear trapezoidal method. Change in the AUC of D6-25(OH)D3 will be calculated as D6-25(OH)D3 AUC measured during CLEAR-PLUS minus D6-25(OH)D3 AUC previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.	Baseline, 6 months
Secondary	Change in 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. Change in the terminal half-life of D6-25(OH)D3 will be calculated as D6-25(OH)D3 half-life measured during CLEAR-PLUS minus D6-25(OH)D3 half-life previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.	Baseline, 6 months
Secondary	Change in 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. Change in the volume of distribution of D6-25(OH)D3 will be calculated as D6-25(OH)D3 volume of distribution measured during CLEAR-PLUS minus D6-25(OH)D3 volume of distribution previously measured during participation in the related study protocol (without vitamin D3 supplementation). Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration. The change listed is between two timepoints.	Baseline, 6 months