Combination of Medium Cut-off Dialyzer Membrane and Diet Modification to Alleviate Residual Uremic Syndrome of Dialysis Patients

Not Applicable

• Conditions: Haemodialysis; Diet, Healthy; End Stage Renal Disease
• Interventions: Device: medium cut-off (MCO) dialysis membrane; Dietary Supplement: Dietary fiber mixture (Plantago Psyllium and Inulin); Dietary Supplement: Sodium propionate

• Registration Number: NCT04247867
• Lead Sponsor: University Medical Centre Ljubljana

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.

Study Timeline

• Study First Submitted: 2020-01-28
• Study First Submitted QC: 2020-01-28
• Study First Posted: 2020-01-30
• Study Start: 2020-08-31
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-17
• Last Update Posted: 2022-05-18
• Primary Completion: 2022-08-30
• Study Completion: 2022-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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);

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Interventional arm - MCO dialysis membrane	Dietary fiber mixture (Plantago Psyllium and Inulin)	4 weeks of dialysis with MCO (Theranova) membrane then dialysis for 4 weeks with MCO membrane and increased fiber intake
Interventional arm - MCO dialysis membrane	medium cut-off (MCO) dialysis membrane	4 weeks of dialysis with MCO (Theranova) membrane then dialysis for 4 weeks with MCO membrane and increased fiber intake
Control arm - high-flux membrane haemodiafiltration	Sodium propionate	4 weeks of high-flux membrane haemodiafiltration and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake
Interventional arm - MCO dialysis membrane	Sodium propionate	4 weeks of dialysis with MCO (Theranova) membrane then dialysis for 4 weeks with MCO membrane and increased fiber intake
Control arm - high-flux membrane haemodiafiltration	Dietary fiber mixture (Plantago Psyllium and Inulin)	4 weeks of high-flux membrane haemodiafiltration and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake

Primary Outcome Measures

Name	Time	Method
Serum concentration of uremic toxin p-cresol sulphate	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 p-cresol sulphate concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.

Secondary Outcome Measures

Name	Time	Method
Serum concentration of uremic toxins indoxyl sulfate	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 indoxyl sulfate concentration will be taken from the arterial line before the start of midweek hemodialysis procedure.

Trial Locations

Locations (1)

University Medical Center ljubljana; 🇸🇮 Ljubljana, Slovenia