Clinical trial NCT04260412: The Effect of Combining Medium Cut Off Dialysis Membrane and Diet Modification on Reducing of Inflammation Response
Official title: The Effect of Combining Medium Cut Off Polyarylethersulfone-polyvinylpyrrolidone Dialysis Membrane and Diet Modification on Reducing of Inflammation Response
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: End Stage Renal Disease
Haemodialysis
Diet, Healthy
Chronic Inflammation
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
First posted: 2020-02-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized, interventional, two parallel arm study.
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Serum concentration of inflammatory mediator interleukin-6 (IL-6).
timeFrame: 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 outcomes:
measure: Serum concentration of inflammatory mediator High-sensitivity C-reactive protein (hs-CRP).
timeFrame: 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 outcomes:
measure: Serum concentration of inflammatory mediator interleukin-10 (IL-10).
timeFrame: 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).
measure: Serum concentration of inflammatory mediator serum amyloid A (SAA).
timeFrame: 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).
measure: Serum leukocyte count.
timeFrame: 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).
measure: Plasma concentration of bacterial 16s rDNA.
timeFrame: 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).
measure: Serum albumin concentration.
timeFrame: 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).
measure: Dialysis symptom index questionnaire score.
timeFrame: 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).
measure: Time to finish 10 repetition sit to stand test.
timeFrame: 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).
measure: Physical activity level as measured by accelerometry.
timeFrame: 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).
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: Nephrology department, University Medical Centre Ljubljana, Slovenia
name: Jernej Pajek, MD, PhD
role: STUDY_CHAIR
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