Renal Insufficiency, ChronicNCT03493087
Underlying Causes of Low Vitamin K Status in Hemodialysis Patients
A study testing Menakinon 7 and Diet rich in vitamin K in people with Renal Insufficiency, Chronic, run by University of Copenhagen at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Insufficiency, Chronic
- What is being tested?
- Menakinon 7 and Diet rich in vitamin K
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteDenmark
- Study dates
- 22 Feb 2018to 20 Nov 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic kidney disease
- Hemodialysis (> 3 months) at Herlev Hospital, Nephrological department
- Understands and are able to read danish
- Able to collaborate on diet etc.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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:
Read more
- The daily intake of vitamin K is insufficient.
- Vitamin K is removed from the blood during dialysis.
- Absorption in the intestines is impaired.
- 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.
Read the detailed 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
- Conditions
- Renal Insufficiency, Chronic
- Being tested
- Menakinon 7, Diet rich in vitamin K
- Keywords
- Dialysis, Vitamin-K, Malnutrition
- Medical subject headings
- Renal Insufficiency, Chronic, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Menakinon 7Dietary supplement
Menakinon 7 - One tablet a day against vitamin K deficiency
Diet rich in vitamin KDietary supplement
Diet with large content of vegetables and dairy products
| Study group | Role | What they receive |
|---|---|---|
| Menakinon-7 | Active comparator | Menakinon-7 360 µg tablet by mouth, every day for 6 weeks Receives: Dietary Supplement: Menakinon 7 |
| Diet with vitamin K | Active comparator | Diet rich in vitamin K for 6 weeks Receives: Dietary Supplement: Diet rich in vitamin K |
What is being measured
The primary outcome is the main question the study is designed to answer.
Δ-dp-uc-MGP (Sub-trial 5)
Comparison of concentration of dp-ucMGP in blood samples through out the intervention
Measured: 15 weeks
Secondary outcomes (13)
dp-ucMGP status (Sub-trial 1)
Concentration of dp-ucMGP in a blood sample collected before dialysis
Measured: 1 day
Vitamin K intake (Sub-trial 1)
Intake of vitamin K is estimated from FFQ results
Measured: 1 month
dp-ucMGP concentration in dialysis water (Sub-trial 2)
A sample of dialysis water is tested for dp-ucMGP
Measured: 1 day
Δ-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
Measured: 1 day
Δ-weight (Sub-trial 2)
The patient's weight before and after dialysis is compared
Measured: 1 day
Concentration of D-xylose (Sub-trial 3)
Concentration of D-xylose in the blood an hour after intake of 15g of D-xylose
Measured: 1 day
Fat in the diet (Sub-trial 3)
The amount of fat in the diet is assessed from FFQ results
Measured: 1 day
Δ-dp-uc-MGP (Sub-trial 4)
intervention with protein is compared with the concentration in a blood sample collected after the intervention
Measured: 14 day
Protein in the diet (Sub-trial 4)
The amount of protein in the diet is assessed from FFQ results
Measured: 14 days
Calcification (Sub-trial 5)
Blood samples are analyzed via calcification propensity score, T50
Measured: 15 weeks
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.
Measured: 15 weeks
The patient's perception of the presence of bruises (Sub-trial 5)
The patient assess the changes in bruising in a questionnaire.
Measured: 15 weeks
Δ-factor 2, 7,10 concentration (Sub-trial 5)
Comparison of concentration of factor 2,7,10 in blood samples before and after both interventions
Measured: 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2018
- Study start22 Feb 2018
- Primary completion20 Aug 2018
- Study completion20 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Insufficiency, ChronicStudies of the same condition, open and under way.
- More trials run by University of CopenhagenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Herlev Hospital
- Responsible party
- Principal investigator, Jens Rikardt Andersen, University of Copenhagen
- Investigators
- Jens Rikardt Andersen, Study director, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03493087
- Sponsor's protocol ID
- H-17036789
- Status last verified
- Apr 2019
- First submitted
- 9 Feb 2018
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Underlying Causes of Low Vitamin K Status in Hemodialysis Patients
- ClinicalTrials.gov ID
- NCT03493087
- Acronym / sponsor ID
- H-17036789
- Conditions
- Renal Insufficiency, Chronic
- Keywords
- Dialysis, Vitamin-K, Malnutrition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of CopenhagenUniversity, hospital or other
- Collaborators
- Herlev Hospital
- Study start
- 22 Feb 2018 (actual)
- Primary completion
- 20 Aug 2018 (actual)
- Study completion
- 20 Nov 2018 (actual)
- First posted
- 10 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- The daily intake of vitamin K is insufficient.
- Vitamin K is removed from the blood during dialysis.
- Absorption in the intestines is impaired.
- 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.
Detailed 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
Study design
- Primary purpose
- Supportive care
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Menakinon-7 | Active comparator | Dietary Supplement: Menakinon 7Menakinon-7 360 µg tablet by mouth, every day for 6 weeks |
| Diet with vitamin K | Active comparator | Dietary Supplement: Diet rich in vitamin KDiet rich in vitamin K for 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Chronic kidney disease
- Hemodialysis (> 3 months) at Herlev Hospital, Nephrological department
- Understands and are able to read danish
- Able to collaborate on diet etc.
Key exclusion criteria (6 listed)
- Warfarin treatment
- Pregnant or breastfeeding
- Prior intake of vitamin K supplements
- Short bowl disease, pancreatitis or other malabsorption diseases/syndromes
- Dementia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Menakinon 7Menakinon 7 - One tablet a day against vitamin K deficiency | Dietary supplement | Menakinon-7 |
| Diet rich in vitamin KDiet with large content of vegetables and dairy products | Dietary supplement | Diet with vitamin K |
Primary outcome
Δ-dp-uc-MGP (Sub-trial 5)
Time frame: 15 weeks
Comparison of concentration of dp-ucMGP in blood samples through out the intervention
13 secondary outcomes
dp-ucMGP status (Sub-trial 1)
Time frame: 1 day
Vitamin K intake (Sub-trial 1)
Time frame: 1 month
dp-ucMGP concentration in dialysis water (Sub-trial 2)
Time frame: 1 day
Δ-concentration of dp-ucMGP (Sub-trial 2)
Time frame: 1 day
Δ-weight (Sub-trial 2)
Time frame: 1 day
Concentration of D-xylose (Sub-trial 3)
Time frame: 1 day
Fat in the diet (Sub-trial 3)
Time frame: 1 day
Δ-dp-uc-MGP (Sub-trial 4)
Time frame: 14 day
Protein in the diet (Sub-trial 4)
Time frame: 14 days
Calcification (Sub-trial 5)
Time frame: 15 weeks
Quality of life (Sub-trial 5)
Time frame: 15 weeks
The patient's perception of the presence of bruises (Sub-trial 5)
Time frame: 15 weeks
Δ-factor 2, 7,10 concentration (Sub-trial 5)
Time frame: 15 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Rikardt Andersen study director
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Menakinon 7 and Diet rich in vitamin K in people with Renal Insufficiency, Chronic, run by University of Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Δ-dp-uc-MGP (Sub-trial 5) (time frame: 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2019.