Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05060809
Other study ID # vit k in hemodialysis patient
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
Start date January 1, 2018
Est. completion date January 1, 2020

Study information

Verified date September 2021
Source Assiut University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Vascular calcification (VC) represents one of the major complications associated with progressive renal impairment. Matrix Gla-protein (MGP) is a vitamin K-dependent protein that acts as a powerful inhibitor of vascular calcification. Despite this fact, it remains unknown whether supplementation with vitamin K can lead to reduction or reversal of vascular and heart valve calcification. Our study aims primarily to investigate the effect of intravenous vitamin K1 three times weekly for a total duration of 6 months on the serum levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP) as well as aortic calcification score and severity of aortic and mitral valve lesions.


Description:

Vascular calcification (VC) represents one of the major complications associated with progressive renal impairment. In addition, VC has been regarded as one of the major predictors of cardiovascular risk, the most common cause of mortality in chronic kidney disease patients (CKD). 65% of end-stage kidney disease (ESKD) patients on regular peritoneal dialysis (PD) and 80-85% of ESKD patients on regular hemodialysis (HD) showed coronary or aortic calcification. These calcifications were associated with the total time on dialysis, with a yearly-increase of vascular calcification by 15% . Traditional risk factors for vascular calcification include age, male gender, smoking, diabetes, hypertension, and dyslipidemia. VC, the pathological deposition of mineral in the vascular system, can manifest as intimal, medial, or heart valve calcification. Whereas intimal calcification, taking place within atherosclerotic plaque in aorta and coronary arteries, indicates advanced atherosclerosis, media calcification, which is often found in patients with diabetes and/or CKD, is characterized by diffuse mineral deposition along elastic fibers in both low resistance elastic-type as well as high resistance muscle-type arteries. Calciphylaxis, or calcific uremic arteriolopathy, represents a special form of ectopic, extraosseous calcification, that is characteristically observed in CKD patients, particularly those with ESKD with additional secondary hyperparathyroidism or those receiving warfarin. A study on hemodialysis patients showed more than two-fold higher odds of aortic and iliac calcifications in patients receiving warfarin than those who do not . VC results from an imbalance of promoters and inhibitors. Matrix Gla-protein (MGP) is a vitamin K-dependent protein and has been found to be expressed by medial vascular smooth muscles of arteries, endothelial cells, chondroblasts, and fibroblasts. Moreover, it is also expressed in the heart, kidneys, and lungs . MGP acts as a powerful inhibitor of vascular calcification. Loss-of-function mutations of MGP was associated with vascular calcification in animal models. In the setting of progressive vascular calcification, MGP transcription increases, giving rise to dephosphorylated-uncarboxylated MGP (dp-ucMGP). This molecule represents the inactive form of MGP, which later undergoes a γ- glutamate carboxylation and serine phosphorylation to produce the active form, phosphorylated carboxylated MGP (p- cMGP). Vitamin K acts as a cofactor for the enzyme γ-glutamylcarboxylase that is responsible for activating dp-ucGMP into dp-cMGP. Despite its key role in activation of dp-ucMGP, it remains unknown whether supplementation with vitamin K can lead to reduction or reversal of vascular and heart valve calcification in hemodialysis patients.


Recruitment information / eligibility

Status Completed
Enrollment 120
Est. completion date January 1, 2020
Est. primary completion date July 30, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Males or females =18 years of age, - Not less than 6 months on HD, - High level of serum dephosphorylated uc-MGP - Signed informed consent, Exclusion Criteria: - Patients with normal level of dp-ucMGP - History of thrombosis, - Intake of vitamin K antagonists (warfarin) at baseline or in the 3 months prior to baseline, - Inflammatory bowel disease, - Liver dysfunction,

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
oral vitamin k1 (phylloquinone)
The enrolled patients received 5 mg of oral vitamin K1 (phylloquinone) three times /week for 6 months at the end of HD session to ensure compliance. We measured the serum dephosphorylated- uncarboxylated matrix Gla protein (dp-ucMGP) before and 6 months after vitamin K1 supplementation. In addition, plain lateral abdominal x-ray was conducted prior to and after 6 months of vitamin K supplementation to assess lumbar aorta calcification. The extent of aortic calcification score (AAC) was assessed by a semi-quantitative grading system developed by Kauppila.

Locations

Country Name City State
Egypt Assiut University Hospital Assiut

Sponsors (1)

Lead Sponsor Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (2)

Aoun M, Makki M, Azar H, Matta H, Chelala DN. High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K(2), A pre-post intervention clinical trial. BMC Nephrol. 2017 Jun 7;18(1):191. doi: 10.1186/s12882-017-0609-3. — View Citation

Krueger T, Schlieper G, Schurgers L, Cornelis T, Cozzolino M, Jacobi J, Jadoul M, Ketteler M, Rump LC, Stenvinkel P, Westenfeld R, Wiecek A, Reinartz S, Hilgers RD, Floege J. Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol. Nephrol Dial Transplant. 2014 Sep;29(9):1633-8. doi: 10.1093/ndt/gft459. Epub 2013 Nov 26. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Effect of vitamin k1 supplementation on vascular calcification Our study aims primarily to investigate the effect of oral vitamin K1 three times weekly for a total duration of 6 months on the serum levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP) as well as aortic calcification score and severity of aortic and mitral valve lesions. 6 months
See also
  Status Clinical Trial Phase
Completed NCT03960437 - The Effect of Etelcalcetide on CKD-MBD Phase 2
Recruiting NCT04983875 - Mammography and Breast Arterial Calcification: An Information-Sharing Trial N/A
Completed NCT03292029 - Pilot Medical Evaluation of the T50 Test N/A
Completed NCT02561299 - Orbital Vessel PreparaTIon to MaximIZe Dcb Efficacy in Calcified Below the Knee (BTK) Lesions - A Pilot Study N/A
Completed NCT00379899 - ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis Phase 4
Active, not recruiting NCT02598635 - Effects of Cholecalciferol on Osteoprotegerin Levels in Patients on Peritoneal Dialysis Phase 4
Completed NCT00183001 - Effect of Vitamin K on Age-Related Bone Loss and Vascular Calcification Phase 3
Completed NCT04114695 - Aortic Calcification and Central Blood Pressure in Patients With Chronic Kidney Disease
Not yet recruiting NCT03169400 - Theranova Dialyzer and Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) N/A
Completed NCT03314493 - Prevention of the Progression of Coronary Calcification With Use of Spironolactone in Peritoneal Dialysis Patients Phase 3
Completed NCT03839732 - Observer Variability in Scoring Abdominal Aortic Calcifications and Vertebral Morphometry
Completed NCT02542319 - Effect of Oral Magnesium on Vascular Calcification in Chronic Kidney Disease Phase 2
Completed NCT02610933 - Effect on Vascular Calcification of Replacing Warfarin by Rivaroxaban With or Without VitK2 in Hemodialysis Patients Phase 4
Completed NCT00481364 - Atorvastatin Treatment to Attenuate the Progression of Cardiovascular Disease in Hemodialysis Patients Phase 3
Completed NCT00694824 - Vascular Calcification's Risk Factors in Haemodialysis Patients
Recruiting NCT01364688 - Oral Alfacalcidol and Coronary Artery Calcification in Predialysis Chronic Kidney Disease Phase 2
Completed NCT01675206 - Dose Defining Study for the Administration of Vitamin K2 Supplements in Hemodialysis Patients Phase 3
Active, not recruiting NCT03937349 - Impact of Parathyroidectomy on Cardiovascular Calcification in Dialysis-dependent Patients
Not yet recruiting NCT05720156 - Immunomodulatory Effects of PCSK9 Inhibition
Completed NCT02719665 - THE OMEGA-SPM-DOSE and OMEGA-SPM-PAD: Specialized Pro-Resolving Mediators in Patients With Peripheral Artery Disease N/A