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

Primary Purpose

Chronic Kidney Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
D6-25-hydroxyvitamin D3
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Chronic Kidney Disease focused on measuring chronic kidney disease, vitamin d catabolism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Washington

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study Population

Arm Description

D6-25-hydroxyvitamin D3

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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
October 14, 2016
Last Updated
August 31, 2021
Sponsor
University of Washington
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT02937350
Brief Title
Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease
Acronym
CLEAR
Official Title
Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
July 8, 2019 (Actual)
Study Completion Date
January 1, 2021 (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 better understand vitamin D catabolism and how it is affected by CKD and race.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease
Keywords
chronic kidney disease, 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
88 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study Population
Arm Type
Experimental
Arm Description
D6-25-hydroxyvitamin D3
Intervention Type
Drug
Intervention Name(s)
D6-25-hydroxyvitamin D3
Other Intervention Name(s)
stable isotope deuterium-labeled 25(OH)D3
Intervention Description
Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
AUC of D6-25(OH)D3
Description
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.
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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
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. Concentration was measured at 5 minutes, 4 hours, and at 1, 4, 7, 14, 21, 28, 42, and 56 days post administration.
Time Frame
8 weeks
Title
Change in the Serum Concentration of Calcium
Description
Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3 administration
Time Frame
7 days
Title
Change in the Serum Concentration of Creatinine
Description
Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3 administration
Time Frame
Baseline, 7 days
Title
Change in the Serum Concentration of AST
Description
Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3 administration
Time Frame
Baseline, 7 days
Title
Change in the Serum Concentration of ALT
Description
Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3 administration
Time Frame
Baseline, 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
98195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33115916
Citation
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.
Results Reference
derived

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Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

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