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

NCT04247867 | Unknown

• 1 other identifier: RIIDTOXINS
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Serum concentration of uremic toxin p-cresol sulphate

  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.

  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 (1)

• 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).

Other Outcomes (8)

• Serum concentration of uremic toxin trimethylamine N-oxide (TMAO)

  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).

• Serum concentration of beta2-microglobulin

  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).

• Serum concentration of phosphate

  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).

Study Arms (2)

Interventional arm - MCO dialysis membrane

EXPERIMENTAL

4 weeks of dialysis with MCO (Theranova) membrane then dialysis for 4 weeks with MCO membrane and increased fiber intake

Device: medium cut-off (MCO) dialysis membrane; Dietary Supplement: Dietary fiber mixture (Plantago Psyllium and Inulin); Dietary Supplement: Sodium propionate

Control arm - high-flux membrane haemodiafiltration

ACTIVE COMPARATOR

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 and Inulin); Dietary Supplement: Sodium propionate

Interventions

medium cut-off (MCO) dialysis membrane DEVICE

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).

Also known as: Theranova dialysis membrane (Baxter AG)

Interventional arm - MCO dialysis membrane

Dietary fiber mixture (Plantago Psyllium and Inulin) DIETARY_SUPPLEMENT

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.

Also known as: Kolon3aktiv fiber powder (manufacturer TOPNATUR s.r.o., Czech republic)

Control arm - high-flux membrane haemodiafiltration; Interventional arm - MCO dialysis membrane

Sodium propionate DIETARY_SUPPLEMENT

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.

Control arm - high-flux membrane haemodiafiltration; Interventional arm - MCO dialysis membrane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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);

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead
• University of Ljubljana: collaborator

Study Sites (1)

University Medical Center ljubljana

Ljubljana, 1000, Slovenia

RECRUITING

Related Publications (18)

• Dobre M, Meyer TW, Hostetter TH. Searching for uremic toxins. Clin J Am Soc Nephrol. 2013 Feb;8(2):322-7. doi: 10.2215/CJN.04260412. Epub 2012 Sep 27.

  PMID: 23024165 BACKGROUND

• Depner TA. Uremic toxicity: urea and beyond. Semin Dial. 2001 Jul-Aug;14(4):246-51. doi: 10.1046/j.1525-139x.2001.00072.x.

  PMID: 11489197 BACKGROUND

• Mostovaya IM, Blankestijn PJ, Bots ML, Covic A, Davenport A, Grooteman MP, Hegbrant J, Locatelli F, Vanholder R, Nube MJ; EUDIAL1 - an official ERA-EDTA Working Group. Clinical evidence on hemodiafiltration: a systematic review and a meta-analysis. Semin Dial. 2014 Mar;27(2):119-27. doi: 10.1111/sdi.12200.

  PMID: 24738146 BACKGROUND

• Wang AY, Ninomiya T, Al-Kahwa A, Perkovic V, Gallagher MP, Hawley C, Jardine MJ. Effect of hemodiafiltration or hemofiltration compared with hemodialysis on mortality and cardiovascular disease in chronic kidney failure: a systematic review and meta-analysis of randomized trials. Am J Kidney Dis. 2014 Jun;63(6):968-78. doi: 10.1053/j.ajkd.2014.01.435. Epub 2014 Mar 28.

  PMID: 24685515 BACKGROUND

• Zweigart C, Boschetti-de-Fierro A, Hulko M, Nilsson LG, Beck W, Storr M, Krause B. Medium cut-off membranes - closer to the natural kidney removal function. Int J Artif Organs. 2017 Jul 5;40(7):328-334. doi: 10.5301/ijao.5000603. Epub 2017 May 26. No abstract available.

  PMID: 28574113 BACKGROUND

• Zickler D, Schindler R, Willy K, Martus P, Pawlak M, Storr M, Hulko M, Boehler T, Glomb MA, Liehr K, Henning C, Templin M, Trojanowicz B, Ulrich C, Werner K, Fiedler R, Girndt M. Medium Cut-Off (MCO) Membranes Reduce Inflammation in Chronic Dialysis Patients-A Randomized Controlled Clinical Trial. PLoS One. 2017 Jan 13;12(1):e0169024. doi: 10.1371/journal.pone.0169024. eCollection 2017.

  PMID: 28085888 BACKGROUND

• Eloot S, Van Biesen W, Glorieux G, Neirynck N, Dhondt A, Vanholder R. Does the adequacy parameter Kt/V(urea) reflect uremic toxin concentrations in hemodialysis patients? PLoS One. 2013 Nov 13;8(11):e76838. doi: 10.1371/journal.pone.0076838. eCollection 2013.

  PMID: 24236005 BACKGROUND

• Montemurno E, Cosola C, Dalfino G, Daidone G, De Angelis M, Gobbetti M, Gesualdo L. What would you like to eat, Mr CKD Microbiota? A Mediterranean Diet, please! Kidney Blood Press Res. 2014;39(2-3):114-23. doi: 10.1159/000355785. Epub 2014 Jul 29.

  PMID: 25117687 BACKGROUND

• Sirich TL. Dietary protein and fiber in end stage renal disease. Semin Dial. 2015 Jan-Feb;28(1):75-80. doi: 10.1111/sdi.12315. Epub 2014 Oct 16.

  PMID: 25319504 BACKGROUND

• Claro LM, Moreno-Amaral AN, Gadotti AC, Dolenga CJ, Nakao LS, Azevedo MLV, de Noronha L, Olandoski M, de Moraes TP, Stinghen AEM, Pecoits-Filho R. The Impact of Uremic Toxicity Induced Inflammatory Response on the Cardiovascular Burden in Chronic Kidney Disease. Toxins (Basel). 2018 Sep 23;10(10):384. doi: 10.3390/toxins10100384.

  PMID: 30249039 BACKGROUND

• Barrajon-Catalan E, Herranz-Lopez M, Joven J, Segura-Carretero A, Alonso-Villaverde C, Menendez JA, Micol V. Molecular promiscuity of plant polyphenols in the management of age-related diseases: far beyond their antioxidant properties. Adv Exp Med Biol. 2014;824:141-59. doi: 10.1007/978-3-319-07320-0_11.

  PMID: 25038998 BACKGROUND

• Moe SM, Zidehsarai MP, Chambers MA, Jackman LA, Radcliffe JS, Trevino LL, Donahue SE, Asplin JR. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011 Feb;6(2):257-64. doi: 10.2215/CJN.05040610. Epub 2010 Dec 23.

  PMID: 21183586 BACKGROUND

• Marzocco S, Fazeli G, Di Micco L, Autore G, Adesso S, Dal Piaz F, Heidland A, Di Iorio B. Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins, A Pilot Study (PLAN Study). J Clin Med. 2018 Sep 30;7(10):315. doi: 10.3390/jcm7100315.

  PMID: 30274359 BACKGROUND

• Kirsch AH, Lyko R, Nilsson LG, Beck W, Amdahl M, Lechner P, Schneider A, Wanner C, Rosenkranz AR, Krieter DH. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transplant. 2017 Jan 1;32(1):165-172. doi: 10.1093/ndt/gfw310.

  PMID: 27587605 BACKGROUND

• Krishnasamy R, Hawley CM, Jardine MJ, Roberts MA, Cho YJ, Wong MG, Heath A, Nelson CL, Sen S, Mount PF, Pascoe EM, Darssan D, Vergara LA, Paul-Brent PA, Toussaint ND, Johnson DW, Hutchison CA. Design and methods of the REMOVAL-HD study: a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HaemoDialysis patients. BMC Nephrol. 2018 Apr 17;19(1):89. doi: 10.1186/s12882-018-0883-8.

  PMID: 29665795 BACKGROUND

• Borges NA, Barros AF, Nakao LS, Dolenga CJ, Fouque D, Mafra D. Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease. J Ren Nutr. 2016 Nov;26(6):396-400. doi: 10.1053/j.jrn.2016.07.005.

  PMID: 27751361 BACKGROUND

• Chapdelaine I, de Roij van Zuijdewijn CL, Mostovaya IM, Levesque R, Davenport A, Blankestijn PJ, Wanner C, Nube MJ, Grooteman MP; EUDIAL Group; Blankestijn PJ, Davenport A, Basile C, Locatelli F, Maduell F, Mitra S, Ronco C, Shroff R, Tattersall J, Wanner C. Optimization of the convection volume in online post-dilution haemodiafiltration: practical and technical issues. Clin Kidney J. 2015 Apr;8(2):191-8. doi: 10.1093/ckj/sfv003. Epub 2015 Feb 16.

  PMID: 25815176 BACKGROUND

• Pajek J, Kveder R, Bren A, Gucek A, Ihan A, Osredkar J, Lindholm B. Short-term effects of a new bicarbonate/lactate-buffered and conventional peritoneal dialysis fluid on peritoneal and systemic inflammation in CAPD patients: a randomized controlled study. Perit Dial Int. 2008 Jan-Feb;28(1):44-52.

  PMID: 18178947 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Psyllium; Inulin; sodium propionate

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures; Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides

Study Officials

• Jernej Pajek, MD, PhD

  Nephrology department, University Medical Centre Ljubljana, Slovenia

  STUDY CHAIR

Central Study Contacts

Jernej Pajek, MD, PhD

CONTACT

+38615228124; jernej.pajek@mf.uni-lj.si

Tjaša Herič, MD

CONTACT

+38615228964; tjasa.heric@kclj.si

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, MD, PhD

Model Details: This is a prospective, randomized, interventional, two parallel arm study.

Study Record Dates

• First Submitted: January 28, 2020
• First Posted: January 30, 2020
• Study Start: August 31, 2020
• Primary Completion: August 30, 2022
• Study Completion: October 31, 2022
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: From the time of publication of associated manuscripts for 10 years.
• Access Criteria: Available on demand from the investigators.

Locations

SL (1)