Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

— CLEAR  

Official title:

Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02937350
• Other study ID #: STUDY00009578
• Secondary ID: R01DK099199
• Status: Completed
• Phase: Phase 1
• Start date: March 1, 2017
• Est. completion date: January 1, 2021

Study information

• Verified date: August 2021
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to better understand vitamin D catabolism and how it is affected by CKD and race.

Description:

Specifically, the study team will evaluate the metabolic clearance of 25-hydroxyvitamin D3 in individuals with varying degrees of CKD and among participants who self-report race as Caucasian, African American or African. The long-term goal of this work is to enhance the clinical evaluation and treatment of impaired vitamin D metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• 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:

• Age = 18 years

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

• Serum total 25(OH)D 10-50 ng/mL

• Estimated GFR:

• 60 mL/min/1.73m2 (N=40) 15-45 mL/min/1.73m2 (N=40) <15 mL/min/1.73m2, treated with hemodialysis (N=40)

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)

• 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 < 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	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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks
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	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	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	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	Baseline, 7 days
Primary	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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks
Secondary	AUC of D6-25(OH)D3	AUC is calculated using the linear trapezoidal method. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks
Secondary	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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks
Secondary	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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks