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

NCT ID: NCT04260412

Last Updated: 2022-05-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-31

Study Completion Date

2022-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

End Stage Renal Disease Haemodialysis Diet, Healthy Chronic Inflammation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a prospective, randomized, interventional, two parallel arm study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Interventional arm - MCO dialysis membrane

4 weeks of dialysis with MCO membrane, then dialysis for 4 weeks with MCO membrane and increased fiber intake

Group Type EXPERIMENTAL

medium cut-off (MCO) dialysis membrane

Intervention Type 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).

Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)

Intervention Type 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.

Sodium propionate

Intervention Type 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

4 weeks of high-flux membrane haemodiafiltration and 4 weeks of high-flux membrane haemodiafiltration and increased fiber intake

Group Type ACTIVE_COMPARATOR

Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)

Intervention Type 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.

Sodium propionate

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

medium cut-off (MCO) dialysis membrane

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).

Intervention Type DEVICE

Dietary fiber mixture (Plantago Psyllium 69% and Inulin 30%)

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.

Intervention Type DIETARY_SUPPLEMENT

Sodium propionate

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.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Theranova dialysis membrane (Baxter AG) Kolon3Aktiv (Topnatur s.r.o., Czech republic)

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Ljubljana

OTHER

Sponsor Role collaborator

University Medical Centre Ljubljana

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jernej Pajek

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jernej Pajek, MD, PhD

Role: STUDY_CHAIR

Nephrology department, University Medical Centre Ljubljana, Slovenia

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Slovenia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Jernej Pajek, MH, PhD

Role: CONTACT

+38615228124

Tjaša Vivoda, MD

Role: CONTACT

+38615228964 ext. +38640587085

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Jernej Pajek, MD, PhD

Role: primary

0038615228124

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 23024165 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11489197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24738146 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24685515 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28574113 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28085888 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24236005 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25117687 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25319504 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30249039 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25038998 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21183586 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30274359 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27587605 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29665795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27751361 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25815176 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18178947 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RIIDINFLAMMATION

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

PERCI- Medium Cut Off (MCO)
NCT02084381 COMPLETED NA
DIALysis With EXpanded Solute Removal
NCT06660277 RECRUITING NA