The Effect of Combining Medium Cut Off Dialysis Membrane and Diet Modification on Reducing of Inflammation Response

May 17, 2022 updated by: Jernej Pajek, University Medical Centre Ljubljana

The Effect of Combining Medium Cut Off Polyarylethersulfone-polyvinylpyrrolidone Dialysis Membrane and Diet Modification on Reducing of Inflammation Response

The investigators purpose is to research the impact of the simultaneous use of a new dialysis membrane with higher permeability for medium and protein bound uraemic toxins (medium cut-off dialysis membrane Theranova®) combined with diet modification to reduce the level of inflammation in chronic dialysis patients. The investigators hypothesize that the use of a medium-cut off dialysis membrane and dietary modification work synergistically and cause a significant and clinically meaningful reduction in inflammation levels compared to on-line hemodiafiltration with a high-flux dialysis membrane.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators will carry out a prospective interventional randomised study to compare achieved serum concentrations of selected protein bound uremic toxins by dialysis with a medium cut-off membrane (Theranova, Baxter AG, USA) and online hemodiafiltration with a standard "high-flux" dialysis membrane. In the second phase, both dialysis purification methods will be supplemented by a change in the diet with increase of the daily intake of dietary fiber to 30g and addition of a short-chain fatty acid propionate in the dose of 1 g daily.

The main outcome of the study is the serum concentration of Interleukin-6. Secondary outcome is the serum concentration of interleukin-10, serum amyloid A, High-sensitivity C-reactive protein, total leukocyte count and plasma concentration of bacterial 16s rDNA. Serum albumin concentration and lean body weight of patients represent safety outcomes for this study.

This investigator-initiated research project has been entirely planned and will be conducted by the clinical researchers in a tertiary hospital University Medical Center Ljubljana.

The study will include 50 chronic prevalent stable dialysis patients in the following periods:

  • 2 weeks of wash-in period with standard bicarbonate haemodialysis and standard high-flux dialysis membrane,
  • then the patients will be randomized in a 1:1 ratio to either one of the two study arms:
  • (interventional study arm) 4 weeks of dialysis with medium cut-off (Theranova) membrane (first phase), then dialysis for 4 weeks with the same membrane and increased fiber intake (second phase),
  • (control study arm) 4 weeks of dialysis with a high-flux membrane using on-line haemodiafiltration (first phase) and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake (second phase),
  • finally, all patients will undergo a 4 week wash-out period with a standard bicarbonate haemodialysis using standard high-flux dialysis membrane identical to wash-in period.

Measurement of the study end-points will be carried out at the end of 2-week wash-in period, each 4-week period and at the end of 4 week wash-out period.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • University Medical Centre Ljubljana
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient on chronic hemodialysis or hemodiafiltration for at least 12 weeks;
  • Age 18 years old or more;
  • A functioning arteriovenous fistula or graft as a permanent dialysis vascular access;
  • Being able to give an informed consent to participate in the survey

Exclusion Criteria:

  • Planned kidney transplantation, transition to peritoneal dialysis or to another dialysis center within 12 weeks of the start of the study
  • Acute febrile inless 4 weeks prior to study inclusion
  • Active chronic inflammation (e.g., an active autoimmune disease or an open wound), chronic ongoing infection or cancer
  • New cardiovascular or cerebrovascular event 4 weeks prior to study inclusion
  • Clinically malnourishet patient and/or BMI below 19 kg/m2 and/or loss of more the 5% of body mass in the last 3 months
  • Immunosuppressive treatment
  • Expected survival of less than 1 year
  • Pregnancy or breast-feeding
  • Indication for dietary supplements to increase calorie and/or protein intake
  • Specific indication for carrying out hemodiafiltration instead of hemodialysis as per attending physician
  • Serum albumin concentration <32 g/l after screening to enter the study
  • Inability to follow the study diet or test procedures
  • Rapid reduction of residual renal function in the period prior to entry into the study
  • Intolerant of on-line haemodiafiltration (infusion intolerance)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Interventional arm - MCO dialysis membrane
4 weeks of dialysis with MCO membrane, then dialysis for 4 weeks with MCO membrane and increased fiber intake
Device: medium cut-off (MCO) dialysis membrane
Medium cut-off dialysis (MCO) membrane is a dialysis membrane with a higher molecular weight retention onset and similar cut-off as standard high-flux dialysis membranes. It is capable of providing increased clearance of medium sized uremic toxins and some plasma proteins (cytokines, inflammatory mediators).
Other Names:
  • Theranova dialysis membrane (Baxter AG)
Dietary supplement: Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)
Dietary fiber (Psyllium 69% and Inulin 30% mixture) added to the meals in the dose of 5g BID for 4 weeks in the second phase of the study.
Other Names:
  • Kolon3Aktiv (Topnatur s.r.o., Czech republic)
Dietary supplement: Sodium propionate
Sodium propionate (a short-chain fatty acid) added to the meals in the dose of 500 mg BID in the second phase in the study.
Active Comparator: Control arm - high-flux membrane haemodiafiltration
4 weeks of high-flux membrane haemodiafiltration and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake
Dietary supplement: Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)
Dietary fiber (Psyllium 69% and Inulin 30% mixture) added to the meals in the dose of 5g BID for 4 weeks in the second phase of the study.
Other Names:
  • Kolon3Aktiv (Topnatur s.r.o., Czech republic)
Dietary supplement: Sodium propionate
Sodium propionate (a short-chain fatty acid) added to the meals in the dose of 500 mg BID in the second phase in the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum concentration of inflammatory mediator interleukin-6 (IL-6).
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of serum total interleukin-6 concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum concentration of inflammatory mediator High-sensitivity C-reactive protein (hs-CRP).
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of serum total hs-CRP concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum concentration of inflammatory mediator interleukin-10 (IL-10).
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of serum total interleukin-10 concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Serum concentration of inflammatory mediator serum amyloid A (SAA).
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of total seum amyloid A concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Serum leukocyte count.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of total serum leukocyte count will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Plasma concentration of bacterial 16s rDNA.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of plasma concentration of bacterial 16s rDNA will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Serum albumin concentration.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Blood for the laboratory measurements of serum albumin concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Dialysis symptom index questionnaire score.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
A validated questionnaire of 30 questions regarding the dialysis symptoms experienced during the last week.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Time to finish 10 repetition sit to stand test.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
This validated test measures lower limb strength. Participants are required to stand up and sit down 10 times from an armless chair as quickly as possible, the outcome is the time needed to perform the test.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Physical activity level as measured by accelerometry.
Time Frame: At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).
Number of accelerometer counts in 7 days.
At the end of wash-in period (basal sample-baseline), at the end of first phase (4 weeks after baseline), at the end of second phase (8 weeks after baseline), at the end of wash-out period (12 weeks after baseline).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Centre Ljubljana

Collaborators

University of Ljubljana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2020

Primary Completion (Anticipated)

August 30, 2022

Study Completion (Anticipated)

October 31, 2022

Study Registration Dates

First Submitted

February 5, 2020

First Submitted That Met QC Criteria

February 5, 2020

First Posted (Actual)

February 7, 2020

Study Record Updates

Last Update Posted (Actual)

May 18, 2022

Last Update Submitted That Met QC Criteria

May 17, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RIIDINFLAMMATION

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Plan to share IPD that underline results published in the manuscripts reporting study results.

IPD Sharing Time Frame

From the time of publication of associated manuscripts for 10 years.

IPD Sharing Access Criteria

Available on demand from the investigators.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on End Stage Renal Disease

Clinical Trials on medium cut-off (MCO) dialysis membrane

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe