Clearance of 25-hydroxyvitamin D in Chronic Kidney Disease

NCT02937350 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: STUDY00009578R01DK099199
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Chronic Kidney Disease

Keywords

chronic kidney disease; vitamin d catabolism

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• AUC of D6-25(OH)D3

  8 weeks

• Terminal Half-life of D6-25(OH)D3

  8 weeks

• Volume of Distribution of D6-25(OH)D3

  8 weeks

Other Outcomes (5)

• Metabolic Formation Clearance of D6-25(OH)D3 Metabolites.

  8 weeks

• Change in the Serum Concentration of Calcium

  7 days

• Change in the Serum Concentration of Creatinine

  Baseline, 7 days

Study Arms (1)

Study Population

EXPERIMENTAL

D6-25-hydroxyvitamin D3

Drug: D6-25-hydroxyvitamin D3

Interventions

D6-25-hydroxyvitamin D3 DRUG

Intravenous administration of a deuterium-labeled 25(OH)D3 to evaluate the metabolic clearance of 25(OH)D3

Also known as: stable isotope deuterium-labeled 25(OH)D3

Study Population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Self-reported race Caucasian, African American, or African
• Serum total 25(OH)D 10-50 ng/mL
• Estimated GFR:
• mL/min/1.73m2 (N=40) 15-45 mL/min/1.73m2 (N=40) \<15 mL/min/1.73m2, treated with hemodialysis (N=40)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (2)

• Best CM, Thummel KE, Hsu S, Lin Y, Zelnick LR, Kestenbaum B, Kushnir MM, de Boer IH, Hoofnagle AN. The plasma free fraction of 25-hydroxyvitamin D3 is not strongly associated with 25-hydroxyvitamin D3 clearance in kidney disease patients and controls. J Steroid Biochem Mol Biol. 2023 Feb;226:106206. doi: 10.1016/j.jsbmb.2022.106206. Epub 2022 Oct 28.

  PMID: 36404469 DERIVED

• 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.

  PMID: 33115916 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Ian de Boer
• Organization: University of Washington

IDeBoer@Nephrology.washington.edu

206-616-5403

Study Officials

• Ian de Boer, MD, MS

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine/Nephrology

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: October 18, 2016
• Study Start: March 1, 2017
• Primary Completion: July 8, 2019
• Study Completion: January 1, 2021
• Last Updated: September 1, 2021
• Results First Posted: September 1, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)