Clinical trial NCT05081960: Evaluating the Vitamin K2 Status of Calcium-based Stone Formers
Official title: Evaluating the Vitamin K2 Status of Calcium-based Stone Formers
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
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
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: St. Joseph's Health Care London
First posted: 2021-10-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fecal microbiota composition of stone-formers and controls
timeFrame: At baseline only
measure: Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)
timeFrame: At baseline only
measure: Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)
timeFrame: At baseline only
measure: Concentration of blood total osteocalcin (OC)
timeFrame: At baseline only
measure: Concentration of blood undercarboxylated osteocalcin (ucOC)
timeFrame: At baseline only
measure: Concentration of urine total osteocalcin (OC)
timeFrame: At baseline only
measure: Concentration of urine undercarboxylated osteocalcin (ucOC)
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-4
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-7
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-8
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-9
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-10
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-11
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-12
timeFrame: At baseline only
measure: Concentration of blood menaquinones (vitamin K2) - MK-13
timeFrame: At baseline only
Secondary outcomes:
measure: Concentration of blood fetuin A
timeFrame: At baseline only
measure: Concentration of urine fetuin A
timeFrame: At baseline only
measure: Percentage of blood Hemoglobin A1C (HbA1c)
timeFrame: At baseline only
measure: Total plasma calcium
timeFrame: At baseline only
measure: Concentration of ionized calcium in blood
timeFrame: At baseline only
measure: Concentration of blood albumin
timeFrame: At baseline only
measure: Concentration of urinary γ-carboxyglutamic acid
timeFrame: At baseline only
measure: Concentration of urinary creatinine
timeFrame: At baseline only
measure: Concentration of urinary oxalate
timeFrame: At baseline only
measure: Concentration of urinary phosphate
timeFrame: At baseline only
Other outcomes:
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care London
state: Ontario
Study officials:
affiliation: Lawson Heath Research
name: Jennifer Bjazevic, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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