Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study) (IMPROVE)

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ClinicalTrials.gov Identifier: NCT03813550

Recruitment Status : Unknown

Verified January 2019 by University Hospital, Angers.
Recruitment status was: Recruiting

First Posted : January 23, 2019

Last Update Posted : February 4, 2019

Sponsor:

Collaborators:

Maastricht University

Biofortis Mérieux NutriSciences

Information provided by (Responsible Party):

University Hospital, Angers

No Study Results Posted on ClinicalTrials.gov for this Study

About Study Results Reporting on ClinicalTrials.gov

Recruitment Status :	Unknown
Estimated Primary Completion Date :	January 30, 2020
Estimated Study Completion Date :	January 30, 2020

Publications:

Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26.

Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25.

Pomozi V, Brampton C, van de Wetering K, Zoll J, Calio B, Pham K, Owens JB, Marh J, Moisyadi S, Váradi A, Martin L, Bauer C, Erdmann J, Aherrahrou Z, Le Saux O. Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice. Am J Pathol. 2017 Jun;187(6):1258-1272. doi: 10.1016/j.ajpath.2017.02.009. Epub 2017 Apr 14.

Gheduzzi D, Boraldi F, Annovi G, DeVincenzi CP, Schurgers LJ, Vermeer C, Quaglino D, Ronchetti IP. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. 2007 Oct;87(10):998-1008. Epub 2007 Aug 27.

Hendig D, Zarbock R, Szliska C, Kleesiek K, Götting C. The local calcification inhibitor matrix Gla protein in pseudoxanthoma elasticum. Clin Biochem. 2008 Apr;41(6):407-12. doi: 10.1016/j.clinbiochem.2007.12.023. Epub 2008 Jan 11.

Li Q, Jiang Q, Schurgers LJ, Uitto J. Pseudoxanthoma elasticum: reduced gamma-glutamyl carboxylation of matrix gla protein in a mouse model (Abcc6-/-). Biochem Biophys Res Commun. 2007 Dec 14;364(2):208-13. Epub 2007 Oct 4.

Vanakker OM, Martin L, Schurgers LJ, Quaglino D, Costrop L, Vermeer C, Pasquali-Ronchetti I, Coucke PJ, De Paepe A. Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome. Lab Invest. 2010 Jun;90(6):895-905. doi: 10.1038/labinvest.2010.68. Epub 2010 Apr 5.

Gorgels TG, Waarsing JH, Herfs M, Versteeg D, Schoensiegel F, Sato T, Schlingemann RO, Ivandic B, Vermeer C, Schurgers LJ, Bergen AA. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum. J Mol Med (Berl). 2011 Nov;89(11):1125-35. doi: 10.1007/s00109-011-0782-y. Epub 2011 Jul 2.

Shearer MJ, Bach A, Kohlmeier M. Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J Nutr. 1996 Apr;126(4 Suppl):1181S-6S. doi: 10.1093/jn/126.suppl_4.1181S. Review.

Ramotar K, Conly JM, Chubb H, Louie TJ. Production of menaquinones by intestinal anaerobes. J Infect Dis. 1984 Aug;150(2):213-8.

Shearer MJ. Vitamin K. Lancet. 1995 Jan 28;345(8944):229-34. Review.

Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr. 2013 Jul 1;4(4):463-73. doi: 10.3945/an.113.003855. Review.

Bentley R, Meganathan R. Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol Rev. 1982 Sep;46(3):241-80. Review.

Conly JM, Stein K. The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Prog Food Nutr Sci. 1992 Oct-Dec;16(4):307-43. Review.

Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K₂) in human health. Br J Nutr. 2013 Oct;110(8):1357-68. doi: 10.1017/S0007114513001013. Epub 2013 Apr 16. Review.

Conly JM, Stein K. Quantitative and qualitative measurements of K vitamins in human intestinal contents. Am J Gastroenterol. 1992 Mar;87(3):311-6.

Schurgers LJ, Teunissen KJ, Hamulyák K, Knapen MH, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007 Apr 15;109(8):3279-83. Epub 2006 Dec 7.

Suttie JW. The importance of menaquinones in human nutrition. Annu Rev Nutr. 1995;15:399-417. Review.

Usui Y, Tanimura H, Nishimura N, Kobayashi N, Okanoue T, Ozawa K. Vitamin K concentrations in the plasma and liver of surgical patients. Am J Clin Nutr. 1990 May;51(5):846-52.

Berkner KL, Runge KW. The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost. 2004 Dec;2(12):2118-32. Review.

Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: the coagulation vitamin that became omnipotent. Thromb Haemost. 2007 Jul;98(1):120-5. Review.

McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009 Oct;90(4):889-907. doi: 10.3945/ajcn.2009.27930. Epub 2009 Aug 19. Review.

Shearer MJ. Role of vitamin K and Gla proteins in the pathophysiology of osteoporosis and vascular calcification. Curr Opin Clin Nutr Metab Care. 2000 Nov;3(6):433-8. Review.

Shanahan CM, Proudfoot D, Farzaneh-Far A, Weissberg PL. The role of Gla proteins in vascular calcification. Crit Rev Eukaryot Gene Expr. 1998;8(3-4):357-75. Review.

Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007 Apr 1;109(7):2823-31.

Li Q, Guo H, Chou DW, Harrington DJ, Schurgers LJ, Terry SF, Uitto J. Warfarin accelerates ectopic mineralization in Abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum. Am J Pathol. 2013 Apr;182(4):1139-50. doi: 10.1016/j.ajpath.2012.12.037. Epub 2013 Feb 15.

Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997 Mar 6;386(6620):78-81.

Theuwissen E, Smit E, Vermeer C. The role of vitamin K in soft-tissue calcification. Adv Nutr. 2012 Mar 1;3(2):166-73. doi: 10.3945/an.111.001628. Review.

Shea MK, O'Donnell CJ, Hoffmann U, Dallal GE, Dawson-Hughes B, Ordovas JM, Price PA, Williamson MK, Booth SL. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr. 2009 Jun;89(6):1799-807. doi: 10.3945/ajcn.2008.27338. Epub 2009 Apr 22.

Vermeer C, Shearer MJ, Zittermann A, Bolton-Smith C, Szulc P, Hodges S, Walter P, Rambeck W, Stöcklin E, Weber P. Beyond deficiency: potential benefits of increased intakes of vitamin K for bone and vascular health. Eur J Nutr. 2004 Dec;43(6):325-35. Epub 2004 Feb 5. Review.

Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5.

Gast GC, de Roos NM, Sluijs I, Bots ML, Beulens JW, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10. doi: 10.1016/j.numecd.2008.10.004. Epub 2009 Jan 28.

Beulens JW, Bots ML, Atsma F, Bartelink ML, Prokop M, Geleijnse JM, Witteman JC, Grobbee DE, van der Schouw YT. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009 Apr;203(2):489-93. doi: 10.1016/j.atherosclerosis.2008.07.010. Epub 2008 Jul 19.

Brandenburg VM, Schurgers LJ, Kaesler N, Püsche K, van Gorp RH, Leftheriotis G, Reinartz S, Koos R, Krüger T. Prevention of vasculopathy by vitamin K supplementation: can we turn fiction into fact? Atherosclerosis. 2015 May;240(1):10-6. doi: 10.1016/j.atherosclerosis.2015.02.040. Epub 2015 Feb 24. Review.

Caluwé R, Pyfferoen L, De Boeck K, De Vriese AS. The effects of vitamin K supplementation and vitamin K antagonists on progression of vascular calcification: ongoing randomized controlled trials. Clin Kidney J. 2016 Apr;9(2):273-9. doi: 10.1093/ckj/sfv146. Epub 2015 Dec 29.

Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015 Aug 7;21(29):8787-803. doi: 10.3748/wjg.v21.i29.8787. Review.

Carrillo-Linares JL, García-Fernández MI, Morillo MJ, Sánchez P, Rioja J, Barón FJ, Ariza MJ, Harrington DJ, Card D, Boraldi F, Quaglino D, Valdivielso P. The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study. Front Med (Lausanne). 2018 Apr 16;5:86. doi: 10.3389/fmed.2018.00086. eCollection 2018.

Brampton C, Yamaguchi Y, Vanakker O, Van Laer L, Chen LH, Thakore M, De Paepe A, Pomozi V, Szabó PT, Martin L, Váradi A, Le Saux O. Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum. Cell Cycle. 2011 Jun 1;10(11):1810-20. Epub 2011 Jun 1.

Karlsson FH, Fåk F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266.

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