Underlying Causes of Low Vitamin K Status in Hemodialysis Patients

Renal Insufficiency, Chronic Clinical Trial

Official title:

Underlying Causes of Low Vitamin K Status in Hemodialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03493087
• Other study ID #: H-17036789
• Status: Completed
• Phase: N/A
• Start date: February 22, 2018
• Est. completion date: November 20, 2018

Study information

• Verified date: April 2019
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Studies have shown that patients with chronic kidney disease in hemodialysis have a low vitamin K status which is believed to be related to an increased risk of atherosclerosis and increased bleeding tendency. The underlying causes of low vitamin K status in hemodialysis patients is unknown. Thus, the aim of this study is to investigate why hemodialysis patients have a low vitamin K status and how to improve it.

This study is composed of five trials. Four of them are based on possible hypotheses to the low vitamin K status. The hypotheses are:

1. The daily intake of vitamin K is insufficient.

2. Vitamin K is removed from the blood during dialysis.

3. Absorption in the intestines is impaired.

4. The analysis method (dephosphorylated-uncarboxylated MGP) is influenced by the patients' protein intake.

The purpose of the fifth trial is to investigate solutions to improve the vitamin K status of hemodialysis. One is to improve vitamin K status through diet with an increased focus on foods with high concentrations of vitamin K while considering phosphate, potassium and fluid restrictions. The second is to increase vitamin K status through a daily supplement of 360µg Menakinon-7.

Description:

Studies have reported a low vitamin K status in chronic kidney disease patients in hemodialysis linked to an increased risk of atherosclerosis and increased bleeding tendency. The overall aim of this study is to investigate the underlying causes of the reported low vitamin K status and to improve the patients' vitamin K status through diet and supplement. The study is divided in 5 sub-trials listed below. Sub-trial 1-4 focuses on determining the underlying course of low vitamin K status while sub-trial 5 deals with possible solutions to the reported low vitamin K status.

The analysis method used to determine vitamin K status is dephosphorylated-uncarboxylated Matrix-Gla-Protein (dp-ucMGP). Dp-ucMGP is the inactive form of the protein MGP whose activation is vitamin K dependent. The dp-ucMGP analysis method is not a direct measure of vitamin K status. However, an increased concentration of dp-ucMGP is a manifestation of a low vitamin K status and vice versa.

Sub-trial 1: Intake of vitamin K Aim: To assess the patients' intake of vitamin K. Hypothesis: The daily intake of vitamin K is insufficient. Method: Patients are asked to fill out a food frequency questionnaire (FFQ). The FFQ is based on their intake of different foods rich in vitamin K during the last month. To compare the results from the FFQ with their actual vitamin K status a blood sample is collected and analyzed to determine dp-ucMGP. Participants: 30.

Sub-trial 2: The influence of dialysis Aim: To examine whether vitamin K status is compromised during dialysis. Hypothesis: Vitamin K is removed from the blood during dialysis. Method: A blood test is collected before and after dialysis and analyzed to determine dp-ucMGP. At the end of the dialysis a sample of the remaining dialysis-water is collected and analyzed to determine dp-ucMGP. Furthermore, the patients will be weighed before and after dialysis with the purpose of calculating concentrations. Participants: 16 (the analysis of the dialysis water is done for five patients at first, if the results are useful the analysis is done for every participant).

Sub-trial 3: Absorption Aim: To investigate whether a decreased absorption can be the cause of the low vitamin K status. Hypothesis: Absorption in the intestines is impaired. Method: A D-xylose test is performed. The participants are given a dose of 15g D-xylose dissolved in water and after one hour a sample of blood is collected to determine D-xylose in serum. Prior to this trial the patients need to be fasting.The patients are asked to fill out a FFQ concerning their intake of fat during the last month. Participants: 16

Sub-trial 4: Concentrations of dp-ucMGP is influenced by a low protein intake. Aim: To determine if a low protein intake influence the dp-ucMGP analysis method. Hypothesis: The analysis method (dephosphorylated-uncarboxylated MGP) is influenced by the patients' protein intake. Method: Patients are given a daily protein supplement for 14 days. Before and after the intervention a blood test is collected and the concentration of dp-ucMGP is determined and compared. Moreover, the patients are asked to fill out a FFQ concerning their intake of protein during the last month. Participants: 16

Sub-trial 5: Intervention with vitamin K Aim: To investigate whether a diet or supplement with tablets is best for improve vitamin K status. Hypothesis: If the intake of vitamin K is insufficient the diet rich in vitamin K should be sufficient. However, if absorption is compromised or vitamin K is influenced by dialysis a larger dose of vitamin K might be necessary. Method: This trial lasts for 15 weeks divided in two periods of six weeks and a three week wash out period in-between. One period focuses on a diet rich in vitamin K while dealing with the possible restrictions on phosphate, potassium and fluid for hemodialysis patients. The intervention in the other period consists of a supplement of 360μg Menakinon-7/day. Blood samples are collected at the beginning, middle and end of both periods. These blood samples are analyzed to determine dp-uc-MGP during the intervention period. Moreover, coagulations factor 2, 7, 10, vitamin A and D status and calcification propency score analysis will be done as well if the funds allow it. Patients are asked to fill out a questionnaire concerning physical and mental wellbeing and the presence of bruising at the beginning and end of both periods to determine whether vitamin K has an effect. Participants: 24

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: November 20, 2018
• Est. primary completion date: August 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic kidney disease

• Hemodialysis (> 3 months) at Herlev Hospital, Nephrological department

• Understands and are able to read danish

• Able to collaborate on diet etc.

Exclusion Criteria:

• Warfarin treatment

• Pregnant or breastfeeding

• Prior intake of vitamin K supplements

• Short bowl disease, pancreatitis or other malabsorption diseases/syndromes

• Dementia

• Diabetes Mellitus (only an exclusion criterion in sub-trial 3: Absorption of vitamin K)

Related Conditions & MeSH terms

• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Menakinon 7
Menakinon 7 - One tablet a day against vitamin K deficiency
• Diet rich in vitamin K
Diet with large content of vegetables and dairy products

Locations

Country	Name	City	State
Denmark	Herlev Hospital	Herlev

Sponsors (2)

Lead Sponsor	Collaborator
University of Copenhagen	Herlev Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Phosphate (Sub-trial 5)	Changes in p-phosphate through out the intervention period	15 weeks
Other	Potassium (Sub-trial 5)	Changes in p-potassium through out the intervention period	15 weeks
Other	Vitamin A (Sub-trial 5)	Changes in p-vitamin A through out the supplement period	15 weeks
Other	Vitamin D (Sub-trial 5)	Changes in p-vitamin D through out the supplement period	15 weeks
Primary	?-dp-uc-MGP (Sub-trial 5)	Comparison of concentration of dp-ucMGP in blood samples through out the intervention	15 weeks
Secondary	dp-ucMGP status (Sub-trial 1)	Concentration of dp-ucMGP in a blood sample collected before dialysis	1 day
Secondary	Vitamin K intake (Sub-trial 1)	Intake of vitamin K is estimated from FFQ results	1 month
Secondary	dp-ucMGP concentration in dialysis water (Sub-trial 2)	A sample of dialysis water is tested for dp-ucMGP	1 day
Secondary	?-concentration of dp-ucMGP (Sub-trial 2)	Concentration of dp-ucMGP in a blood sample collected before dialysis is compared with the concentration in a blood sample collected after dialysis	1 day
Secondary	?-weight (Sub-trial 2)	The patient's weight before and after dialysis is compared	1 day
Secondary	Concentration of D-xylose (Sub-trial 3)	Concentration of D-xylose in the blood an hour after intake of 15g of D-xylose	1 day
Secondary	Fat in the diet (Sub-trial 3)	The amount of fat in the diet is assessed from FFQ results	1 day
Secondary	?-dp-uc-MGP (Sub-trial 4)	intervention with protein is compared with the concentration in a blood sample collected after the intervention	14 day
Secondary	Protein in the diet (Sub-trial 4)	The amount of protein in the diet is assessed from FFQ results	14 days
Secondary	Calcification (Sub-trial 5)	Blood samples are analyzed via calcification propensity score, T50	15 weeks
Secondary	Quality of life (Sub-trial 5)	The results from mental and physical well being questionnaires are compared Based on SF-36 Danish version. Eight questions with scales ranges from 1-5 with 5 being the worse outcome. The questions are looked at individually and together.	15 weeks
Secondary	The patient's perception of the presence of bruises (Sub-trial 5)	The patient assess the changes in bruising in a questionnaire.	15 weeks
Secondary	?-factor 2, 7,10 concentration (Sub-trial 5)	Comparison of concentration of factor 2,7,10 in blood samples before and after both interventions	15 weeks