Clinical trial NCT04247867: Combination of Medium Cut-off Dialyzer Membrane and Diet Modification to Alleviate Residual Uremic Syndrome of Dialysis Patients
Official title: Combination of Medium Cut-off Dialyzer Membrane and Diet Modification to Alleviate Residual Uremic Syndrome of Dialysis Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: End Stage Renal Disease
Haemodialysis
Diet, Healthy
Keywords: medium cut-off dialysis membrane
p-cresol sulphate
indoxyl-sulphate
trimethylamine-N-oxide (TMAO)
hemodiafiltration
uremic toxins
dietary fibre
end stage renal disease
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Ljubljana
First posted: 2020-01-30
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 study will compare achieved levels of protein-bound uremic toxins with dialysis using a medium cut-off membrane compared to the treatment by online haemodiafiltration with a high-flux dialysis membrane. In the second phase of the study dietary fiber and short-chain fatty acid intake will be increased to verify a possible additional reduction in the levels of protein bound uremic toxins.

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 p-cresol sulphate. Secondary outcome is the serum concentration of indoxyl-sulphate and trimethylamine-N-oxide (TMAO). 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 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,
* active chronic inflammation (e.g., an active autoimmune disease or an open wound), chronic ongoing infection or cancer in last 4 weeks,
* acute febrile illness in last 4 weeks,
* new cardiovascular or neurovascular event in last 4 weeks,
* a need for hospitalization in the last 4 weeks,
* clinically evident malnutrition and/or body mass index of 19 kg/m2 and/or loss of body weight for 5% in 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 at 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 uremic toxin p-cresol sulphate
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 uremic toxins indoxyl sulfate
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 uremic toxin trimethylamine N-oxide (TMAO)
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 beta2-microglobulin
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 phosphate
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 urea 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: 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 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 Center ljubljana
Study officials:
affiliation: Nephrology department, University Medical Centre Ljubljana, Slovenia
name: Jernej Pajek, MD, PhD
role: STUDY_CHAIR
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