Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

NCT ID: NCT05081960

Last Updated: 2025-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

60 participants

Study Classification

OBSERVATIONAL

Study Start Date

2022-08-01

Study Completion Date

2025-06-08

Brief Summary

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This is an observation, single site-study with one study visit during which all data and samples will be collected. Study participants will be asked to provide blood, urine, and fecal samples so that the investigators may study the differences in the gut microbiota, vitamin K2 levels, and other parameters between participants who form kidney stones and those who do not.

Detailed Description

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It is hypothesized that calcium-based stone formers will have an altered fecal gut microbiota compared to non-stone former controls. This altered microbiota will have a lower abundance of bacteria that produce menaquinones (vitamin K2), thus stone formers will also have a different blood menaquinone profile compared to controls. Ultimately, the different levels of menaquinones will result in increased inactive Matrix Gla protein (dp-ucMGP), which is a key protein that sequesters free calcium. To test this hypothesis, calcium-based stone former and non-stone forming controls will be recruited to a single site, observation study to collect urine, blood, and fecal samples. These samples will be used to determine dp-ucMGP levels, menaquinone profiles, the composition of the gut microbiota, and other parameters of interest.

Conditions

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Kidney Calculi Calcium Oxalate Kidney Stones Vitamin K 2 Human Kidney Stone Calcium Oxalate Urolithiasis Calcium Phosphate Urolithiasis Nephrolithiasis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Stone Formers

Individuals who have experienced at least one incidence of calcium-based kidney stones in the last 12 months

No interventions assigned to this group

Controls

Individuals who have never had a kidney stone in their lifetime.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Male/Female, 18 - 65 years old
* No self-reported kidney stones during their lifetime (controls)
* Ultrasound examination confirming absence of kidney stones (controls)
* Have had at least 1 incidence of a clinically confirmed calcium-based kidney stone in the last 12 months (stone formers)
* Ability to collect a clean catch urine sample
* Prescription and over-the-counter drugs unchanged for ≥30 days
* Willingness to provide medical information, blood, urine, and fecal samples

Exclusion Criteria

* Current, or within 30 days, use of antibiotics or antifungals
* Current, or within 30 days, use of vitamin K antagonists
* Current probiotic use or any use within 14 days of screening sample collection should be recorded
* A history or currently undergoing immunosuppressive drug therapy, chemotherapy, or radiation therapy 2021-06-29 1.0 Page 4 of 6
* Fecal incontinence
* History of disorder with abnormal calcium regulation such as hyperparathyroidism, active malignancy, or osteoporosis.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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St. Joseph's Health Care London

OTHER

Sponsor Role collaborator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role lead

Responsible Party

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Jennifer Bjazevic

Principal Investigator, MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jennifer Bjazevic, MD

Role: PRINCIPAL_INVESTIGATOR

Lawson Heath Research

Locations

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St. Joseph's Health Care London

London, Ontario, Canada

Site Status

Countries

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Canada

References

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Conly J, Stein K. Reduction of vitamin K2 concentrations in human liver associated with the use of broad spectrum antimicrobials. Clin Invest Med. 1994 Dec;17(6):531-9.

Reference Type BACKGROUND
PMID: 7895417 (View on PubMed)

Fraser JD, Price PA. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem. 1988 Aug 15;263(23):11033-6.

Reference Type BACKGROUND
PMID: 3042764 (View on PubMed)

Moe OW. Kidney stones: pathophysiology and medical management. Lancet. 2006 Jan 28;367(9507):333-44. doi: 10.1016/S0140-6736(06)68071-9.

Reference Type BACKGROUND
PMID: 16443041 (View on PubMed)

Sato T, Schurgers LJ, Uenishi K. Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women. Nutr J. 2012 Nov 12;11:93. doi: 10.1186/1475-2891-11-93.

Reference Type BACKGROUND
PMID: 23140417 (View on PubMed)

Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012 Jul;62(1):160-5. doi: 10.1016/j.eururo.2012.03.052. Epub 2012 Mar 31.

Reference Type BACKGROUND
PMID: 22498635 (View on PubMed)

Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis. 2000 Nov-Dec;30(6):298-307. doi: 10.1159/000054147.

Reference Type BACKGROUND
PMID: 11356998 (View on PubMed)

Schurgers LJ, Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim Biophys Acta. 2002 Feb 15;1570(1):27-32. doi: 10.1016/s0304-4165(02)00147-2.

Reference Type BACKGROUND
PMID: 11960685 (View on PubMed)

Stanford J, Charlton K, Stefoska-Needham A, Ibrahim R, Lambert K. The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature. BMC Nephrol. 2020 Jun 5;21(1):215. doi: 10.1186/s12882-020-01805-w.

Reference Type BACKGROUND
PMID: 32503496 (View on PubMed)

Wei FF, Thijs L, Zhang ZY, Jacobs L, Yang WY, Salvi E, Citterio L, Cauwenberghs N, Kuznetsova T, E A Drummen N, Hara A, Manunta P, Li Y, Verhamme P, Allegaert K, Cusi D, Vermeer C, Staessen JA. The risk of nephrolithiasis is causally related to inactive matrix Gla protein, a marker of vitamin K status: a Mendelian randomization study in a Flemish population. Nephrol Dial Transplant. 2018 Mar 1;33(3):514-522. doi: 10.1093/ndt/gfx014.

Reference Type BACKGROUND
PMID: 28340119 (View on PubMed)

Chmiel JA, Stuivenberg GA, Al KF, Akouris PP, Razvi H, Burton JP, Bjazevic J. Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome. Nat Rev Urol. 2023 Oct;20(10):615-637. doi: 10.1038/s41585-023-00768-5. Epub 2023 May 9.

Reference Type BACKGROUND
PMID: 37161031 (View on PubMed)

Other Identifiers

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119537

Identifier Type: -

Identifier Source: org_study_id

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