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

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ClinicalTrials.gov Identifier: NCT04260412
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : May 18, 2022
Sponsor:
Collaborator:
University of Ljubljana
Information provided by (Responsible Party):
Jernej Pajek, University Medical Centre Ljubljana

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Haemodialysis Diet, Healthy Chronic Inflammation Device: medium cut-off (MCO) dialysis membrane Dietary Supplement: Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%) Dietary Supplement: Sodium propionate Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a prospective, randomized, interventional, two parallel arm study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effect of Combining Medium Cut Off Polyarylethersulfone-polyvinylpyrrolidone Dialysis Membrane and Diet Modification on Reducing of Inflammation Response
Actual Study Start Date : August 31, 2020
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : October 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis

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 Name: 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 Name: 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 Name: 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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04260412


Contacts
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Contact: Jernej Pajek, MH, PhD +38615228124 jernej.pajek@mf.uni-lj.si
Contact: Tjaša Vivoda, MD +38615228964 ext +38640587085 tjasa.vivoda@kclj.si

Locations
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Slovenia
University Medical Centre Ljubljana Recruiting
Ljubljana, Slovenia, 1000
Contact: Jernej Pajek, MD, PhD    0038615228124    jernej.pajek@mf.uni-lj.si   
Sponsors and Collaborators
University Medical Centre Ljubljana
University of Ljubljana
Investigators
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Study Chair: Jernej Pajek, MD, PhD Nephrology department, University Medical Centre Ljubljana, Slovenia
Publications:

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Responsible Party: Jernej Pajek, MD, PhD, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT04260412    
Other Study ID Numbers: RIIDINFLAMMATION
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Plan to share IPD that underline results published in the manuscripts reporting study results.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: From the time of publication of associated manuscripts for 10 years.
Access Criteria: Available on demand from the investigators.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Failure, Chronic
Inflammation
Pathologic Processes
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Psyllium
Cathartics
Gastrointestinal Agents