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Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation (CLEAR-PLUS)

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:

  • 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

Sites / Locations

  • University of Washington

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study Population

Arm Description

D6-25-hydroxyvitamin D3 with vitamin D3

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
June 22, 2018
Last Updated
May 14, 2022
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
NCT03576716
Brief Title
Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation
Acronym
CLEAR-PLUS
Official Title
Clearance of 25-hydroxyvitamin D3 During Vitamin D3 Supplementation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (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 determine how 25(OH)D3 clearance is affected by vitamin D3 supplementation using a gold standard pharmacokinetic approach.
Detailed 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.

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
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study Population
Arm Type
Experimental
Arm Description
D6-25-hydroxyvitamin D3 with vitamin 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
Change in 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. 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.
Time Frame
Baseline, 6 months
Secondary Outcome Measure Information:
Title
Change in AUC of D6-25(OH)D3
Description
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.
Time Frame
Baseline, 6 months
Title
Change in 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. 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.
Time Frame
Baseline, 6 months
Title
Change in 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. 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.
Time Frame
Baseline, 6 months
Other Pre-specified Outcome Measures:
Title
Changes in 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. 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.
Time Frame
Baseline, 6 months
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. The change listed is between two timepoints.
Time Frame
Baseline, 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. The change listed is between two timepoints.
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. The change listed is between two timepoints.
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. The change listed is between two timepoints.
Time Frame
Baseline, 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
IPD Sharing Plan Description
Coded individual participant data may be shared with other researchers under mutually agreeable terms.
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 D3 During Vitamin D3 Supplementation

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