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CLEAR: Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT02937350
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
88
Enrollment
1
Location
1
Arm
46.1
Actual Duration (Months)
1.9
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: D6-25-hydroxyvitamin D3
 Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
88 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Diagnostic
Official Title:
Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease
Actual Study Start Date :
Mar 1, 2017
Actual Primary Completion Date :
Jul 8, 2019
Actual Study Completion Date :
Jan 1, 2021

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Metabolic Clearance of D6-25(OH)D3 [8 weeks]

      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

    1. AUC of D6-25(OH)D3 [8 weeks]

      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.

    2. Terminal Half-life of D6-25(OH)D3 [8 weeks]

      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.

    3. Volume of Distribution of D6-25(OH)D3 [8 weeks]

      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.

    Other Outcome Measures

    1. Metabolic Formation Clearance of D6-25(OH)D3 Metabolites. [8 weeks]

      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.

    2. Change in the Serum Concentration of Calcium [7 days]

      Change in the serum concentration of calcium from baseline to 7 days after 25(OH)D3 administration

    3. Change in the Serum Concentration of Creatinine [Baseline, 7 days]

      Change in the serum concentration of creatinine from baseline to 7 days after 25(OH)D3 administration

    4. Change in the Serum Concentration of AST [Baseline, 7 days]

      Change in the serum concentration of AST from baseline to 7 days after 25(OH)D3 administration

    5. Change in the Serum Concentration of ALT [Baseline, 7 days]

      Change in the serum concentration of ALT from baseline to 7 days after 25(OH)D3 administration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Washington Seattle Washington United States 98195

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Ian de Boer, MD, MS, University of Washington

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Ian deBoer, Professor, Medicine/Nephrology, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02937350
    Other Study ID Numbers:
    • STUDY00009578
    • R01DK099199
    First Posted:
    Oct 18, 2016
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Ian deBoer, Professor, Medicine/Nephrology, University of Washington
    chronic kidney disease
    vitamin d catabolism
    Additional relevant MeSH terms:
    Kidney Diseases
    Renal Insufficiency, Chronic
    Hydroxycholecalciferols
    Calcifediol

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Period Title: Overall Study
    STARTED 43 25 20
    COMPLETED 43 24 20
    NOT COMPLETED 0 1 0

    Baseline Characteristics

    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group Total
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis Total of all reporting groups
    Overall Participants 43 24 20 87
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    64
    (10)
    67
    (11)
    58
    (9)
    64
    (11)
    Sex: Female, Male (Count of Participants)
    Female
    24
    55.8%
    8
    33.3%
    4
    20%
    36
    41.4%
    Male
    19
    44.2%
    16
    66.7%
    16
    80%
    51
    58.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    12
    27.9%
    8
    33.3%
    6
    30%
    26
    29.9%
    White
    31
    72.1%
    16
    66.7%
    14
    70%
    61
    70.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Vitamin-D3 Supplement Use (participants) [Number]
    Number [participants]
    6
    14%
    1
    4.2%
    1
    5%
    8
    9.2%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [milliliter per day (ml/d)]
    360
    (108)
    313
    (86)
    263
    (163)
    2. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [nanograms x day/mL (ngxd/mL)]
    59.8
    (10.2)
    68.7
    (10.2)
    76.6
    (12.0)
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [days (d)]
    21.9
    (5.7)
    25.5
    (6.5)
    35.6
    (8.1)
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [Liters (L)]
    11.0
    (2.9)
    11.1
    (2.8)
    12.5
    (4.0)
    5. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [ratio]
    0.12
    (0.04)
    0.08
    (0.03)
    0.03
    (0.03)
    6. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [milligrams/deciliter (mg/dl)]
    0.42
    (1.75)
    0.16
    (0.26)
    -0.27
    (0.48)
    7. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [milligrams/deciliter (mg/dl)]
    0.04
    (0.09)
    -0.05
    (0.27)
    2.81
    (2.26)
    8. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [units/Liter (u/L)]
    0.40
    (3.43)
    0.57
    (5.98)
    0.10
    (5.22)
    9. Other Pre-specified Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Healthy Controls CKD Group Kidney Failure Group
    Arm/Group Description Healthy controls defined as normal eGFR (>60 ml/min per 1.73m2) CKD group defined as those with eGFR <60ml/min per 1.73 m2) Kidney failure group defined as those with ESKD treated with dialysis
    Measure Participants 43 24 20
    Mean (Standard Deviation) [units/Liter (u/L)]
    0.16
    (3.71)
    1.52
    (6.92)
    0.45
    (3.66)

    Adverse Events

    Time Frame 8 weeks
    Adverse Event Reporting Description Everyone had the same treatment, so it was more appropriate to summarize AEs for the whole group. Adverse events were not collected separately per arm.
    Arm/Group Title All Participants
    Arm/Group Description All participants (N=87)
    All Cause Mortality
    All Participants
    Affected / at Risk (%) # Events
    Total 0/87 (0%)
    Serious Adverse Events
    All Participants
    Affected / at Risk (%) # Events
    Total 1/87 (1.1%)
    Blood and lymphatic system disorders
    Deep vein thrombosis 1/87 (1.1%)
    Other (Not Including Serious) Adverse Events
    All Participants
    Affected / at Risk (%) # Events
    Total 16/87 (18.4%)
    General disorders
    Pain or sensation in arm during infusion 16/87 (18.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Ian de Boer
    Organization University of Washington
    Phone 206-616-5403
    Email IDeBoer@Nephrology.washington.edu
    Responsible Party:
    Ian deBoer, Professor, Medicine/Nephrology, University of Washington
    ClinicalTrials.gov Identifier:
    NCT02937350
    Other Study ID Numbers:
    • STUDY00009578
    • R01DK099199
    First Posted:
    Oct 18, 2016
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021