Ignite Creation Date:
2025-12-25 @ 2:06 AM
Ignite Modification Date:
2025-12-27 @ 10:30 AM
Study NCT ID:
NCT05081960
Status:
COMPLETED
Last Update Posted:
2025-07-22
First Post:
2021-09-22
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluating the Vitamin K2 Status of Calcium-based Stone Formers
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007669', 'term': 'Kidney Calculi'}, {'id': 'C563477', 'term': 'Nephrolithiasis, Calcium Oxalate'}, {'id': 'D053040', 'term': 'Nephrolithiasis'}], 'ancestors': [{'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052878', 'term': 'Urolithiasis'}, {'id': 'D014545', 'term': 'Urinary Calculi'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D002137', 'term': 'Calculi'}, {'id': 'D020763', 'term': 'Pathological Conditions, Anatomical'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Urine, fecal, and blood samples will be collected.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 60}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2022-08-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2025-06-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-07-17', 'studyFirstSubmitDate': '2021-09-22', 'studyFirstSubmitQcDate': '2021-10-05', 'lastUpdatePostDateStruct': {'date': '2025-07-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-10-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-06-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Fecal microbiota composition of stone-formers and controls', 'timeFrame': 'At baseline only', 'description': 'Fecal samples will be collected using out validated toilet paper method. Microbial DNA will be extracted and sequenced using next-generation sequencing.'}, {'measure': 'Concentration of urine dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)', 'timeFrame': 'At baseline only', 'description': 'dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of blood dp-ucMGP (dephosphorylated-uncarboxylated Matrix Gla Protein)', 'timeFrame': 'At baseline only', 'description': 'dp-ucMGP will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of blood total osteocalcin (OC)', 'timeFrame': 'At baseline only', 'description': 'Total OC will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of blood undercarboxylated osteocalcin (ucOC)', 'timeFrame': 'At baseline only', 'description': 'ucOC will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of urine total osteocalcin (OC)', 'timeFrame': 'At baseline only', 'description': 'Total OC will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of urine undercarboxylated osteocalcin (ucOC)', 'timeFrame': 'At baseline only', 'description': 'ucOC will be quantified using an enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-4', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-7', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-8', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-9', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-10', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-11', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-12', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}, {'measure': 'Concentration of blood menaquinones (vitamin K2) - MK-13', 'timeFrame': 'At baseline only', 'description': 'Menaquinones will be quantified using liquid chromatography with mass spectrometry or fluorescence.'}], 'secondaryOutcomes': [{'measure': 'Concentration of blood fetuin A', 'timeFrame': 'At baseline only', 'description': 'Fetuin A will be quantified using enzyme-linked immunosorbent assay'}, {'measure': 'Concentration of urine fetuin A', 'timeFrame': 'At baseline only', 'description': 'Fetuin A will be quantified using enzyme-linked immunosorbent assay'}, {'measure': 'Percentage of blood Hemoglobin A1C (HbA1c)', 'timeFrame': 'At baseline only', 'description': 'HbA1c will be quantified in the core laboratory as per established protocols'}, {'measure': 'Total plasma calcium', 'timeFrame': 'At baseline only', 'description': 'Calcium levels will be quantified in the core laboratory'}, {'measure': 'Concentration of ionized calcium in blood', 'timeFrame': 'At baseline only', 'description': 'Calcium levels will be quantified in the core laboratory'}, {'measure': 'Concentration of blood albumin', 'timeFrame': 'At baseline only', 'description': 'Albumin levels will be quantified in the core laboratory as per established protocols'}, {'measure': 'Concentration of urinary γ-carboxyglutamic acid', 'timeFrame': 'At baseline only', 'description': 'γ-carboxyglutamic acid will be quantified using high-performance liquid chromatography and normalized to creatinine'}, {'measure': 'Concentration of urinary creatinine', 'timeFrame': 'At baseline only', 'description': 'Creatinine will be quantified using high-performance liquid chromatography'}, {'measure': 'Concentration of urinary oxalate', 'timeFrame': 'At baseline only', 'description': 'Oxalate will be quantified using high-performance liquid chromatography and normalized to creatinine'}, {'measure': 'Concentration of urinary phosphate', 'timeFrame': 'At baseline only', 'description': 'Phosphate will be quantified in the core laboratory as per established protocols'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Kidney stone disease', 'Microbiota', 'Menaquinone', 'Vitamin K2', 'Matrix Gla protein', 'dp-ucMGP', 'Nephrolithiasis'], 'conditions': ['Kidney Calculi', 'Calcium Oxalate Kidney Stones', 'Vitamin K 2', 'Human', 'Kidney Stone', 'Calcium Oxalate Urolithiasis', 'Calcium Phosphate Urolithiasis', 'Nephrolithiasis']}, 'referencesModule': {'references': [{'pmid': '7895417', 'type': 'BACKGROUND', '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.'}, {'pmid': '3042764', 'type': 'BACKGROUND', '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.'}, {'pmid': '16443041', 'type': 'BACKGROUND', '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.'}, {'pmid': '23140417', 'type': 'BACKGROUND', '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.'}, {'pmid': '22498635', 'type': 'BACKGROUND', '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.'}, {'pmid': '11356998', 'type': 'BACKGROUND', '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.'}, {'pmid': '11960685', 'type': 'BACKGROUND', '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.'}, {'pmid': '32503496', 'type': 'BACKGROUND', '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.'}, {'pmid': '28340119', 'type': 'BACKGROUND', '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 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': '37161031', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Stone formers will be recruited from the Urology clinic or London and surrounding community. Controls will be recruited from the London and surrounding community.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male/Female, 18 - 65 years old\n* No self-reported kidney stones during their lifetime (controls)\n* Ultrasound examination confirming absence of kidney stones (controls)\n* Have had at least 1 incidence of a clinically confirmed calcium-based kidney stone in the last 12 months (stone formers)\n* Ability to collect a clean catch urine sample\n* Prescription and over-the-counter drugs unchanged for ≥30 days\n* Willingness to provide medical information, blood, urine, and fecal samples\n\nExclusion Criteria:\n\n* Current, or within 30 days, use of antibiotics or antifungals\n* Current, or within 30 days, use of vitamin K antagonists\n* Current probiotic use or any use within 14 days of screening sample collection should be recorded\n* A history or currently undergoing immunosuppressive drug therapy, chemotherapy, or radiation therapy 2021-06-29 1.0 Page 4 of 6\n* Fecal incontinence\n* History of disorder with abnormal calcium regulation such as hyperparathyroidism, active malignancy, or osteoporosis.'}, 'identificationModule': {'nctId': 'NCT05081960', 'briefTitle': 'Evaluating the Vitamin K2 Status of Calcium-based Stone Formers', 'organization': {'class': 'OTHER', 'fullName': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's"}, 'officialTitle': 'Evaluating the Vitamin K2 Status of Calcium-based Stone Formers', 'orgStudyIdInfo': {'id': '119537'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Stone Formers', 'description': 'Individuals who have experienced at least one incidence of calcium-based kidney stones in the last 12 months'}, {'label': 'Controls', 'description': 'Individuals who have never had a kidney stone in their lifetime.'}]}, 'contactsLocationsModule': {'locations': [{'zip': 'N6J 3T9', 'city': 'London', 'state': 'Ontario', 'country': 'Canada', 'facility': "St. Joseph's Health Care London", 'geoPoint': {'lat': 42.98339, 'lon': -81.23304}}], 'overallOfficials': [{'name': 'Jennifer Bjazevic, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Lawson Heath Research'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's", 'class': 'OTHER'}, 'collaborators': [{'name': "St. Joseph's Health Care London", 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator, MD', 'investigatorFullName': 'Jennifer Bjazevic', 'investigatorAffiliation': "London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's"}}}}