Vitamin K to Slow Progression of Cardiovascular Disease Risk in Hemodialysis Patients

Vitamin K to Slow Progression of Cardiovascular Disease Risk in Hemodialysis Patients (Vita-K 'n' CKD Study)

The life span of adults with end-stage renal disease is reduced, and cardiovascular disease (CVD) accounts for approximately half the deaths among those undergoing hemodialysis (HD). Vascular calcification is a key process in the development of atherosclerotic and arteriosclerotic CVD, and contributes significantly to the greater mortality rates and CVD events in HD patients. Recently, there has been growing interest in the vitamin K-dependent matrix Gla protein (MGP) and its role in inhibiting vascular calcification. Animal studies have revealed that the vitamin K-dependent protein MGP may reduce the progression of vascular calcification, possibly by means of improving vascular function. The relationship between MGP and vitamin K lies in the fact that inactive matrix Gla protein requires vitamin K to carboxylate it for its activation. Currently, data in HD patients are scant and equivocal on the effects of vitamin K supplementation on CVD risk outcomes. Therefore, the purpose of this 8-week randomized, placebo-controlled, double-blind clinical trial is to determine whether daily vitamin K supplementation can favorably alter measurements of endothelial function and arterial stiffness in HD patients.

Study Overview

• Status: Unknown
• Conditions: Cardiovascular Diseases; Hemodialysis; Chronic Kidney Disease Stage 5; Chronic Kidney Disease Stage 3; Chronic Kidney Disease Stage 4; Vitamin K Deficiency
• Intervention / Treatment: Dietary supplement: Placebo-Control; Dietary supplement: Vitamin K2 (menaquinone-7; 360-mcg/d)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Recruiting
      • Augusta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic Kidney Disease Stages 3 to 5
• Receiving hemodialysis treatment for at least 3 months
• Subject understands the study protocol and agrees to comply with it
• Informed consent documents signed by subject

Exclusion Criteria:

• Using vitamin supplements containing vitamin K
• History of metabolic gastrointestinal diseases
• Subjects presenting chronic degenerative and/or inflammatory diseases
• Receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters (salicylates, antibiotics)
• Subjects receiving corticosteroid
• Use of anticoagulants
• History of soy allergy
• Have an unstable medical condition, such as having a life expectancy of less than 6 months in the judgment of the investigator
• Known sensitivity, intolerance, or other adverse response to study drugs which would prevent compliance with study medication
• Subjects who have participated in a clinical study more recently than one month before the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo-Control; The placebo-control group will take four placebo softgel capsules (similar in taste and appearance to the vitamin K2 supplements) every day for 8 weeks.	Dietary supplement: Placebo-Control; four placebo softgel capsules per day for 8 weeks containing no vitamin K2 (menaquinone-7)
EXPERIMENTAL: Vitamin K2 (360-mcg/d); The experimental group will take four 90-mcg of vitamin K2 (menaquinone-7; 360-mcg) softgel capsules every day for 8 weeks.	Dietary supplement: Vitamin K2 (menaquinone-7; 360-mcg/d); four 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Mediated Dilation (FMD)	The FMD test is non-invasive assessment of vascular endothelial function.	Change from baseline to 8 weeks
Pulse Wave Velocity (PWV)	The PWV test is a non-invasive test of arterial stiffness.	Change from baseline to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prothrombin Time	The prothrombin time test is a measurement of clotting time.	Change from baseline to 8 weeks

Collaborators and Investigators

• Sponsor: Augusta University
• Investigators: Principal Investigator: Norman K Pollock, PhD, Augusta University

Publications and helpful links

General Publications

• Fain ME, Kapuku GK, Paulson WD, Williams CF, Raed A, Dong Y, Knapen MHJ, Vermeer C, Pollock NK. Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in African American Hemodialysis Patients. Am J Hypertens. 2018 May 7;31(6):735-741. doi: 10.1093/ajh/hpy049.

Helpful Links

• Principal Investigator - Faculty Profile

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 13, 2017
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 30, 2021

Study Registration Dates

• First Submitted: October 9, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (ACTUAL): October 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Endothelial Function; Arterial Stiffness; Vitamin K
• Additional Relevant MeSH Terms: Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Nutrition Disorders; Hemorrhagic Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Blood Coagulation Disorders; Cardiovascular Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Vitamin K Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Vitamin K 2; Vitamin MK 7
• Other Study ID Numbers: 683534

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Approximate date of when the data will be shared? 2019-06-01; Where will the data be made available? The de-identified data will be made available for research purposes only by contacting the principal investigator.; Please explain any limits to data sharing that might be required. Even though the final research data will be stripped of identifiers prior to release for sharing, the investigators believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics. Thus, the principal investigator will make the data available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Time Frame: The data will become available on June 1, 2019 for approximately 12 months.
• IPD Sharing Access Criteria: The principal investigator will make the data available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No