Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease (CLEAR)

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

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: D6-25-hydroxyvitamin D3

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Study Population; D6-25-hydroxyvitamin D3	Drug: D6-25-hydroxyvitamin D3; Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3; Other Names: stable isotope deuterium-labeled 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. 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.	8 weeks
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Hsu S, Zelnick LR, Lin YS, Best CM, Kestenbaum B, Thummel KE, Rose LM, Hoofnagle AN, de Boer IH. Differences in 25-Hydroxyvitamin D Clearance by eGFR and Race: A Pharmacokinetic Study. J Am Soc Nephrol. 2021 Jan;32(1):188-198. doi: 10.1681/ASN.2020050625. Epub 2020 Oct 28.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 8, 2019
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: October 14, 2016
• First Submitted That Met QC Criteria: October 14, 2016
• First Posted (Estimate): October 18, 2016

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: chronic kidney disease; vitamin d catabolism
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcifediol; Hydroxycholecalciferols
• Other Study ID Numbers: STUDY00009578; R01DK099199 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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