Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

NCT05081960 | Completed

• 1 other identifier: 119537
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Kidney stone disease; Microbiota; Menaquinone; Vitamin K2; Matrix Gla protein; dp-ucMGP; Nephrolithiasis

Outcome Measures

Primary Outcomes (15)

• Fecal microbiota composition of stone-formers and controls

  Fecal samples will be collected using out validated toilet paper method. Microbial DNA will be extracted and sequenced using next-generation sequencing.

  At baseline only

• Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)

  dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)

  dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of blood total osteocalcin (OC)

  Total OC will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of blood undercarboxylated osteocalcin (ucOC)

  ucOC will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of urine total osteocalcin (OC)

  Total OC will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of urine undercarboxylated osteocalcin (ucOC)

  ucOC will be quantified using an enzyme-linked immunosorbent assay

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-4

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-7

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-8

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-9

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-10

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-11

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-12

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

• Concentration of blood menaquinones (vitamin K2) - MK-13

  Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

  At baseline only

Secondary Outcomes (10)

• Concentration of blood fetuin A

  At baseline only

• Concentration of urine fetuin A

  At baseline only

• Percentage of blood Hemoglobin A1C (HbA1c)

  At baseline only

• Total plasma calcium

  At baseline only

• Concentration of ionized calcium in blood

  At baseline only

Study Arms (2)

Stone Formers

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

Controls

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Stone formers will be recruited from the Urology clinic or London and surrounding community. Controls will be recruited from the London and surrounding community.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• St. Joseph's Health Care London: collaborator

Study Sites (1)

St. Joseph's Health Care London

London, Ontario, N6J 3T9, Canada

Location

Related Publications (10)

• 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.

  PMID: 7895417 BACKGROUND

• 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.

  PMID: 3042764 BACKGROUND

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

  PMID: 16443041 BACKGROUND

• 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.

  PMID: 23140417 BACKGROUND

• 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.

  PMID: 22498635 BACKGROUND

• 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.

  PMID: 11356998 BACKGROUND

• 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.

  PMID: 11960685 BACKGROUND

• 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.

  PMID: 32503496 BACKGROUND

• 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.

  PMID: 28340119 BACKGROUND

• 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.

  PMID: 37161031 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Urine, fecal, and blood samples will be collected.

MeSH Terms

Conditions

Kidney Calculi; Nephrolithiasis, Calcium Oxalate; Nephrolithiasis

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urolithiasis; Urinary Calculi; Male Urogenital Diseases; Calculi; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer Bjazevic, MD

  Lawson Heath Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: October 18, 2021
• Study Start: August 1, 2022
• Primary Completion: June 8, 2023
• Study Completion: June 8, 2025
• Last Updated: July 22, 2025

Record last verified: 2024-08

Locations

CA (1)