Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

Kidney Stone Clinical Trial

Official title:

Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05081960
• Other study ID #: 119537
• Status: Active, not recruiting
• Start date: August 1, 2022
• Est. completion date: October 2023

Study information

• Verified date: June 2023
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: October 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Calcium Oxalate Urolithiasis
• Calculi
• Human
• Kidney Calculi
• Kidney Stone
• Nephrolithiasis
• Urinary Calculi
• Urolithiasis
• Vitamin K 2

Locations

Country	Name	City	State
Canada	St. Joseph's Health Care London	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	St. Joseph's Health Care London

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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 May 9:1-23. doi: 10.1038/s41585-023-00768-5. Online ahead of print. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 m — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)	dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)	dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of blood total osteocalcin (OC)	Total OC will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of blood undercarboxylated osteocalcin (ucOC)	ucOC will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of urine total osteocalcin (OC)	Total OC will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of urine undercarboxylated osteocalcin (ucOC)	ucOC will be quantified using an enzyme-linked immunosorbent assay	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-4	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-7	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-8	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-9	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-10	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-11	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-12	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Primary	Concentration of blood menaquinones (vitamin K2) - MK-13	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.	At baseline only
Secondary	Concentration of blood fetuin A	Fetuin A will be quantified using enzyme-linked immunosorbent assay	At baseline only
Secondary	Concentration of urine fetuin A	Fetuin A will be quantified using enzyme-linked immunosorbent assay	At baseline only
Secondary	Percentage of blood Hemoglobin A1C (HbA1c)	HbA1c will be quantified in the core laboratory as per established protocols	At baseline only
Secondary	Total plasma calcium	Calcium levels will be quantified in the core laboratory	At baseline only
Secondary	Concentration of ionized calcium in blood	Calcium levels will be quantified in the core laboratory	At baseline only
Secondary	Concentration of blood albumin	Albumin levels will be quantified in the core laboratory as per established protocols	At baseline only
Secondary	Concentration of urinary ?-carboxyglutamic acid	?-carboxyglutamic acid will be quantified using high-performance liquid chromatography and normalized to creatinine	At baseline only
Secondary	Concentration of urinary creatinine	Creatinine will be quantified using high-performance liquid chromatography	At baseline only
Secondary	Concentration of urinary oxalate	Oxalate will be quantified using high-performance liquid chromatography and normalized to creatinine	At baseline only
Secondary	Concentration of urinary phosphate	Phosphate will be quantified in the core laboratory as per established protocols	At baseline only