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

Not Applicable

• Conditions: End Stage Renal Disease; Haemodialysis; Diet, Healthy; Chronic Inflammation

• Registration Number: NCT04260412
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2020-02-05
• Study First Submitted QC: 2020-02-05
• Study First Posted: 2020-02-07
• 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
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Serum concentration of inflammatory mediator interleukin-6 (IL-6).	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

Name	Time	Method
Serum concentration of inflammatory mediator High-sensitivity C-reactive protein (hs-CRP).	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.

Trial Locations

Locations (1)

University Medical Centre Ljubljana; 🇸🇮 Ljubljana, Slovenia