Vitamin K2 Supplementation and Vascular Calcification

NCT04539418 | Completed Phase 4 DMC

• 1 other identifier: UCASAL-VITK
• Study Type: interventional
• Target: 59
• Locations: 0 countries
• Sites: N/A

Brief Summary

Vascular calcification is the leading cause of death in patients with end stage renal disease (ESRD) in hemodialysis. The protein matrix Gla vitamin K dependent (MGP) is a potent inhibitor of the vascular calcification. Objective: To evaluate the effect of vitamin K2 on vascular calcification in patients on hemodialysis. Materials and Methods: A prospective, randomized, double-blind study will be performed. The study subjects will be divided into a control (1000 µl of saline) or treated group (1000 µl containing 2000 µg of Vitamin K2). Vitamin K2 will be administered three times a week intravenously at the end of each dialysis session. Blood samples for biochemical determinations and vascular calcification will be assessed before and after 6 months of treatment through carotid Doppler ultrasound.

Conditions

Renal Disease

Keywords

Hemodialysis patients; Vascular calcification; Vitamin K2

Outcome Measures

Primary Outcomes (3)

• EFFECT OF VITAMIN K2 ON VASCULAR CALCIFICATION

  Changes in the VC (changes in the intimate thickness of carotide artery versus baseline).

  6 months

• CHANGES IN THE PRODUCT PHOSPHORUS CALCIUM

  Changes in the product phosphorus calcium versus baseline

  6 months

• CHANGES IN PTHi SERUM LEVELS

  Not significant changes in PTHi serum levels versus baseline

  6 months

Study Arms (2)

Vitamn K2 Treated patients

ACTIVE COMPARATOR

Vitamin K2 will be given to patients randomized to ARM 1 three times a week at the end of each dialysis session to prevent it being lost through the ultrafiltration membrane (in order to use the same dialysis access) intravenously to ensure its bioavailability.

Drug: Vitamin K 2

Placebo Group

PLACEBO COMPARATOR

Placebo will be given to patients randomized three times a week to ARM 2 at the end of each dialysis session to prevent it being lost through the ultrafiltration membrane (in order to use the same dialysis access) intravenously to ensure its bioavailability.

Drug: Vitamin K 2

Interventions

Vitamin K 2 DRUG

Patients will be monitored during the whole protocol.

Also known as: PLACEBO GROUP

Placebo Group; Vitamn K2 Treated patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women ≥18 years old
• A period not less than 6 months in HD
• Life expectancy ≥ 18 months
• Signed informed consent

You may not qualify if:

• Patients under treatment with phosphorus chelators
• Patients who do not want to participate in the study

Sponsors & Collaborators

• Catholic University of Salta: lead

Related Publications (32)

• Vo TM, Disthabanchong S. Are there ways to attenuate arterial calcification and improve cardiovascular outcomes in chronic kidney disease? World J Cardiol. 2014 May 26;6(5):216-26. doi: 10.4330/wjc.v6.i5.216.

  PMID: 24944752 RESULT

• Georgianos PI, Pikilidou MI, Liakopoulos V, Balaskas EV, Zebekakis PE. Arterial stiffness in end-stage renal disease-pathogenesis, clinical epidemiology, and therapeutic potentials. Hypertens Res. 2018 May;41(5):309-319. doi: 10.1038/s41440-018-0025-5. Epub 2018 Mar 12.

  PMID: 29531291 RESULT

• Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004 Aug;15(8):2208-18. doi: 10.1097/01.ASN.0000133041.27682.A2.

  PMID: 15284307 RESULT

• Brandenburg VM, Schurgers LJ, Kaesler N, Pusche K, van Gorp RH, Leftheriotis G, Reinartz S, Koos R, Kruger 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.

  PMID: 25744701 RESULT

• Caluwe 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.

  PMID: 26985380 RESULT

• Caluwe R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese AS. Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant. 2014 Jul;29(7):1385-90. doi: 10.1093/ndt/gft464. Epub 2013 Nov 26.

  PMID: 24285428 RESULT

• Cannata-Andia JB, Rodriguez-Garcia M, Carrillo-Lopez N, Naves-Diaz M, Diaz-Lopez B. Vascular calcifications: pathogenesis, management, and impact on clinical outcomes. J Am Soc Nephrol. 2006 Dec;17(12 Suppl 3):S267-73. doi: 10.1681/ASN.2006080925.

  PMID: 17130273 RESULT

• Cranenburg EC, Schurgers LJ, Uiterwijk HH, Beulens JW, Dalmeijer GW, Westerhuis R, Magdeleyns EJ, Herfs M, Vermeer C, Laverman GD. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012 Sep;82(5):605-10. doi: 10.1038/ki.2012.191. Epub 2012 May 30.

  PMID: 22648294 RESULT

• Scheiber D, Veulemans V, Horn P, Chatrou ML, Potthoff SA, Kelm M, Schurgers LJ, Westenfeld R. High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification. Nutrients. 2015 Aug 18;7(8):6991-7011. doi: 10.3390/nu7085318.

  PMID: 26295257 RESULT

• De Vriese AS, Caluwe R, Bailleul E, De Bacquer D, Borrey D, Van Vlem B, Vandecasteele SJ, Emmerechts J. Dose-finding study of rivaroxaban in hemodialysis patients. Am J Kidney Dis. 2015 Jul;66(1):91-8. doi: 10.1053/j.ajkd.2015.01.022. Epub 2015 Mar 21.

  PMID: 25804678 RESULT

• Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000 May 18;342(20):1478-83. doi: 10.1056/NEJM200005183422003.

  PMID: 10816185 RESULT

• Gundberg CM, Lian JB, Booth SL. Vitamin K-dependent carboxylation of osteocalcin: friend or foe? Adv Nutr. 2012 Mar 1;3(2):149-57. doi: 10.3945/an.112.001834.

  PMID: 22516722 RESULT

• Hur DJ, Raymond GV, Kahler SG, Riegert-Johnson DL, Cohen BA, Boyadjiev SA. A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome. Am J Med Genet A. 2005 May 15;135(1):36-40. doi: 10.1002/ajmg.a.30680.

  PMID: 15810001 RESULT

• Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Nakamura T, Sato T, Yamazaki K. Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab. 2009;27(1):66-75. doi: 10.1007/s00774-008-0008-8. Epub 2008 Dec 12.

  PMID: 19082528 RESULT

• January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. No abstract available.

  PMID: 24685669 RESULT

• Jono S, Nishizawa Y, Shioi A, Morii H. Parathyroid hormone-related peptide as a local regulator of vascular calcification. Its inhibitory action on in vitro calcification by bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1997 Jun;17(6):1135-42. doi: 10.1161/01.atv.17.6.1135.

  PMID: 9194765 RESULT

• Kaesler N, Magdeleyns E, Herfs M, Schettgen T, Brandenburg V, Fliser D, Vermeer C, Floege J, Schlieper G, Kruger T. Impaired vitamin K recycling in uremia is rescued by vitamin K supplementation. Kidney Int. 2014 Aug;86(2):286-93. doi: 10.1038/ki.2013.530. Epub 2014 Jan 15.

  PMID: 24429407 RESULT

• Kruger T, Floege J. Vitamin K antagonists: beyond bleeding. Semin Dial. 2014 Jan-Feb;27(1):37-41. doi: 10.1111/sdi.12175.

  PMID: 24400802 RESULT

• London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003 Sep;18(9):1731-40. doi: 10.1093/ndt/gfg414.

  PMID: 12937218 RESULT

• Malluche HH, Monier-Faugere MC. Understanding and managing hyperphosphatemia in patients with chronic renal disease. Clin Nephrol. 1999 Nov;52(5):267-77.

  PMID: 10584989 RESULT

• Moe SM, Chen NX. Mechanisms of vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2008 Feb;19(2):213-6. doi: 10.1681/ASN.2007080854. Epub 2007 Dec 19.

  PMID: 18094365 RESULT

• Szczerba E. [Summary of the article: Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med, 2011; 365: 1557-1559]. Kardiol Pol. 2012;70(1):102-3. No abstract available. Polish.

  PMID: 22267443 RESULT

• Pucaj K, Rasmussen H, Moller M, Preston T. Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7. Toxicol Mech Methods. 2011 Sep;21(7):520-32. doi: 10.3109/15376516.2011.568983. Epub 2011 Jul 25.

  PMID: 21781006 RESULT

• Rumberger JA, Brundage BH, Rader DJ, Kondos G. Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc. 1999 Mar;74(3):243-52. doi: 10.4065/74.3.243.

  PMID: 10089993 RESULT

• Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM. Exploring the biology of vascular calcification in chronic kidney disease: what's circulating? Kidney Int. 2008 Feb;73(4):384-90. doi: 10.1038/sj.ki.5002696. Epub 2007 Nov 28.

  PMID: 18046319 RESULT

• Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, Vermeer C, Choukroun G, Massy ZA. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol. 2010 Apr;5(4):568-75. doi: 10.2215/CJN.07081009. Epub 2010 Feb 4.

  PMID: 20133489 RESULT

• Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM. Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation. 2008 Oct 21;118(17):1748-57. doi: 10.1161/CIRCULATIONAHA.108.783738. Epub 2008 Oct 6.

  PMID: 18838561 RESULT

• Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr. 2012 Nov 14;108(9):1652-7. doi: 10.1017/S0007114511007185. Epub 2012 Jan 31.

  PMID: 22289649 RESULT

• Vissers LE, Dalmeijer GW, Boer JM, Monique Verschuren WM, van der Schouw YT, Beulens JW. Intake of dietary phylloquinone and menaquinones and risk of stroke. J Am Heart Assoc. 2013 Dec 10;2(6):e000455. doi: 10.1161/JAHA.113.000455.

  PMID: 24326161 RESULT

• Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95. doi: 10.1053/j.ajkd.2011.10.041. Epub 2011 Dec 9.

  PMID: 22169620 RESULT

• Winkelmayer WC, Patrick AR, Liu J, Brookhart MA, Setoguchi S. The increasing prevalence of atrial fibrillation among hemodialysis patients. J Am Soc Nephrol. 2011 Feb;22(2):349-57. doi: 10.1681/ASN.2010050459. Epub 2011 Jan 13.

  PMID: 21233416 RESULT

• Zhang YT, Tang ZY. Research progress of warfarin-associated vascular calcification and its possible therapy. J Cardiovasc Pharmacol. 2014 Jan;63(1):76-82. doi: 10.1097/FJC.0000000000000008.

  PMID: 24072176 RESULT

MeSH Terms

Conditions

Kidney Diseases; Vascular Calcification

Interventions

Vitamin K 2

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Rocío Pérez Abud, PhD

  Universidad Católica de Salta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Patients are assigned to groups through computer-generated randomization. The investigator will know about the randomization and he will give the care provider the saline or vitamin K2
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective, randomized, double-blind study

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 7, 2020
• Study Start: December 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: June 30, 2017
• Last Updated: September 9, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share