Evaluating the Vitamin K2 Status of Calcium-based Stone Formers

Active, not recruiting

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

• Registration Number: NCT05081960
• Lead Sponsor: Lawson Health Research Institute

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-09-22
• Study First Submitted QC: 2021-10-05
• Study First Posted: 2021-10-18
• Study Start: 2022-08-01
• Primary Completion: 2023-06-08
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-15
• Last Update Posted: 2024-08-19
• Study Completion: 2025-06-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Concentration of blood menaquinones (vitamin K2) - MK-12	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)	At baseline only	dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay
Concentration of blood undercarboxylated osteocalcin (ucOC)	At baseline only	ucOC will be quantified using an enzyme-linked immunosorbent assay
Concentration of urine undercarboxylated osteocalcin (ucOC)	At baseline only	ucOC will be quantified using an enzyme-linked immunosorbent assay
Concentration of blood menaquinones (vitamin K2) - MK-7	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Fecal microbiota composition of stone-formers and controls	At baseline only	Fecal samples will be collected using out validated toilet paper method. Microbial DNA will be extracted and sequenced using next-generation sequencing.
Concentration of blood menaquinones (vitamin K2) - MK-4	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of blood menaquinones (vitamin K2) - MK-9	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)	At baseline only	dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay
Concentration of blood total osteocalcin (OC)	At baseline only	Total OC will be quantified using an enzyme-linked immunosorbent assay
Concentration of blood menaquinones (vitamin K2) - MK-10	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of urine total osteocalcin (OC)	At baseline only	Total OC will be quantified using an enzyme-linked immunosorbent assay
Concentration of blood menaquinones (vitamin K2) - MK-13	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of blood menaquinones (vitamin K2) - MK-8	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.
Concentration of blood menaquinones (vitamin K2) - MK-11	At baseline only	Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.

Secondary Outcome Measures

Name	Time	Method
Concentration of urinary phosphate	At baseline only	Phosphate will be quantified in the core laboratory as per established protocols
Percentage of blood Hemoglobin A1C (HbA1c)	At baseline only	HbA1c will be quantified in the core laboratory as per established protocols
Concentration of urinary oxalate	At baseline only	Oxalate will be quantified using high-performance liquid chromatography and normalized to creatinine
Concentration of urinary creatinine	At baseline only	Creatinine will be quantified using high-performance liquid chromatography
Concentration of blood fetuin A	At baseline only	Fetuin A will be quantified using enzyme-linked immunosorbent assay
Concentration of urine fetuin A	At baseline only	Fetuin A will be quantified using enzyme-linked immunosorbent assay
Concentration of ionized calcium in blood	At baseline only	Calcium levels will be quantified in the core laboratory
Concentration of blood albumin	At baseline only	Albumin levels will be quantified in the core laboratory as per established protocols
Total plasma calcium	At baseline only	Calcium levels will be quantified in the core laboratory
Concentration of urinary γ-carboxyglutamic acid	At baseline only	γ-carboxyglutamic acid will be quantified using high-performance liquid chromatography and normalized to creatinine

Trial Locations

Locations (1)

St. Joseph's Health Care London; 🇨🇦 London, Ontario, Canada