PRObiotics for KIdney Transplantation

NCT06825117 | Enrolling By Invitation

• 1 other identifier: 64/2024
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess if dietary supplememtation with OMNi-BiOTiC® 41167 reduces the risk of urinary tract infections in kidney transplant recipients. It will also assess whether it reduces the risk of graft rejection, modify immunosuppressive regimen, improves post-transplant gastrointestinal and bladder microbiome, gastrointestinal symptoms and quality of life. The main questions it aims to answer are:

• Does daily intake of OMNi-BiOTiC® 41167 reduce the incidence and number of episodes of urinary tract infections?
• Does daily intake of OMNi-BiOTiC® 41167 reduce the incidence and number of episodes of acute graft rejection?
• Does dietary supplementation with OMNi-BiOTiC® 41167 modify gut and bladder microbiome?
• Does dietary supplementation with OMNi-BiOTiC® 41167 modify tacrolimus metabolism and immunosuppressive state?
• Does dietary supplementation with OMNi-BiOTiC® 41167 improves gastrointestinal symptoms and quality of life? Researchers will compare drug OMNi-BiOTiC® 41167 to a placebo (a look-alike substance that contains no drug) to see if OMNi-BiOTiC® 41167 exerts any clinically relevant beneficial effect. Participants will:
• Take OMNi-BiOTiC® 41167 or a placebo every day for 6 months
• Undergo clinical surveillance with seriated visit the clinics for checkups and laboratory analysis
• Provide seriated urine and stool samples for microbiome analysis
• Respond to seriated questionnaire on gastrointestinal symptoms and quality of life

Conditions

Urinary Tract Infections; Kidney Transplant Rejection; Kidney Transplant Infection; Dysbiosis

Outcome Measures

Primary Outcomes (2)

• Urinary tract infection rates

  UTI will be diagnosed based on seriated urine microbiological cultures. Type of bacteria isolated, bacterial load and antibiogram will be also recorded and confronted

  from postoperative month 1 to postoperative month 7

• Rates of Urinary tract symptoms

  Urinary tract symptoms will be assessed and diagnosed with seriated ACSS (Acute Cystitis Symptom Score, 0-39; the higher the score, the worse the severity) questionnaires

  from postoperative month 1 to postoperative month 7

Secondary Outcomes (6)

• Rate of biopsy proven acute rejection

  from postoperative month 1 to postoperative month 7

• Immunosuppression therapy

  from postoperative month 1 to postoperative month 7

• Immunosuppression strength

  from postoperative month 1 to postoperative month 7

• Kidney graft function

  from postoperative month 1 to postoperative month 7

• Gut microbiome

  at postoperative month 1 and postoperative month 7

Other Outcomes (3)

• Quality of life according to SF-12 questionnaire

  from postoperative month 1 to postoperative month 7

• Gastrointestinal symptoms according to GSRS-IBS questionnaire

  from postoperative month 1 to postoperative month 7

• Adverse events

  from postoperative month 1 to postoperative month 7

Study Arms (2)

Probiotic group

EXPERIMENTAL

Dietary Supplement: OMNi-BiOTiC® 41167

Placebo group

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

OMNi-BiOTiC® 41167 DIETARY_SUPPLEMENT

The probiotic OMNi-BiOTiC® 41167 consists of 3g of 3 x 10\^9 CFU total L. gasseri W15, L. plantarum W1, L. plantarum W21, B. lactis W51, L. acidophilus W70 and L. reuteri W192 per sachet of which two are to be taken each day. Additional non-probiotic components are cranberry-extract (0.01g), D-mannose (0,4 g), vitamin D (2,25µg), maize starch and hydrolyzed rice protein. All the strains in OMNi-BiOTiC® 41167 are specifically tested and selected for their inhibition potential against the known most common uropathogens like the uropathogenic Escherichia coli (UPEC), Klebsiella pneumonia, Proteus mirabilis and Entercoccus faecalis.

Probiotic group

Placebo DIETARY_SUPPLEMENT

The placebo consists of all components of OMNi-BiOTiC® 41167, except the probiotic bacteria, cranberry-extract, D-mannose and vitamin D. It has the same smell, taste and texture as the OMNi-BiOTiC® 41167.

Placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• willingness and capability to provide written informed consent/assent for the trial;
• ≥18 and \<75 years of age on day of signing informed consent;
• patients at 30 days post kidney transplantation with surgically uneventful course during the first postoperative month

You may not qualify if:

• pediatric patients (\<18 years)
• elderly patients (\>75 years)
• combined transplantation recipients
• patients with pre-transplant inflammatory bowel disease or irritable bowel syndrome (according to Roma criteria), previous bowel resection or stoma;
• pre-/probiotic supplementation within 1 month of study commencement or use of other probiotics-containing products during the intervention period;
• any proven gastrointestinal infection or disorder during the first post-transplant month or at the time of study enrollment;
• any surgical complication during the first post-transplant month or at the time of study enrollment;
• evidence of ongoing acute rejection, urinary tract infection or other medical complications at the time of enrollment
• known intolerance or allergy to any of the ingredients in both OMNi-BiOTiC® 41167 and placebo

Sponsors & Collaborators

• University Hospital, Udine, Italy: lead
• Winclove Probiotics B.V.: collaborator
• Institut AllergoSan: collaborator

Study Sites (1)

Presidio Ospedaliero Universitario S. Maria della Misericordia, ASUFC

Udine, 33100, Italy

Location

Related Publications (11)

• Winichakoon P, Chaiwarith R, Chattipakorn N, Chattipakorn SC. Impact of gut microbiota on kidney transplantation. Transplant Rev (Orlando). 2022 Jan;36(1):100668. doi: 10.1016/j.trre.2021.100668. Epub 2021 Oct 18.

  PMID: 34688985 BACKGROUND

• Liu S, Liu H, Chen L, Liang SS, Shi K, Meng W, Xue J, He Q, Jiang H. Effect of probiotics on the intestinal microbiota of hemodialysis patients: a randomized trial. Eur J Nutr. 2020 Dec;59(8):3755-3766. doi: 10.1007/s00394-020-02207-2. Epub 2020 Feb 28.

  PMID: 32112136 BACKGROUND

• Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, Scott K, Stanton C, Swanson KS, Cani PD, Verbeke K, Reid G. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017 Aug;14(8):491-502. doi: 10.1038/nrgastro.2017.75. Epub 2017 Jun 14.

  PMID: 28611480 BACKGROUND

• Zaza G, Dalla Gassa A, Felis G, Granata S, Torriani S, Lupo A. Impact of maintenance immunosuppressive therapy on the fecal microbiome of renal transplant recipients: Comparison between an everolimus- and a standard tacrolimus-based regimen. PLoS One. 2017 May 24;12(5):e0178228. doi: 10.1371/journal.pone.0178228. eCollection 2017.

  PMID: 28542523 BACKGROUND

• Coussement J, Maggiore U, Manuel O, Scemla A, Lopez-Medrano F, Nagler EV, Aguado JM, Abramowicz D; European Renal Association-European Dialysis Transplant Association (ERA-EDTA) Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) working group and the European Study Group for Infections in Compromised Hosts (E; COLLABORATORS (IN ALPHABETICAL ORDER); European Renal Association-European Dialysis Transplant Association (ERA-EDTA) Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) working group and the European Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Diagnosis and management of asymptomatic bacteriuria in kidney transplant recipients: a survey of current practice in Europe. Nephrol Dial Transplant. 2018 Sep 1;33(9):1661-1668. doi: 10.1093/ndt/gfy078.

  PMID: 29635410 BACKGROUND

• Eikmans M, Gielis EM, Ledeganck KJ, Yang J, Abramowicz D, Claas FFJ. Non-invasive Biomarkers of Acute Rejection in Kidney Transplantation: Novel Targets and Strategies. Front Med (Lausanne). 2019 Jan 8;5:358. doi: 10.3389/fmed.2018.00358. eCollection 2018.

  PMID: 30671435 BACKGROUND

• Garcia-Martinez Y, Borriello M, Capolongo G, Ingrosso D, Perna AF. The Gut Microbiota in Kidney Transplantation: A Target for Personalized Therapy? Biology (Basel). 2023 Jan 20;12(2):163. doi: 10.3390/biology12020163.

  PMID: 36829442 BACKGROUND

• Przybycinski J, Drozdzal S, Wilk A, Dziedziejko V, Szumilas K, Pawlik A. The Effect of the Gut Microbiota on Transplanted Kidney Function. Int J Mol Sci. 2023 Jan 9;24(2):1260. doi: 10.3390/ijms24021260.

  PMID: 36674775 BACKGROUND

• Strohaeker J, Aschke V, Koenigsrainer A, Nadalin S, Bachmann R. Urinary Tract Infections in Kidney Transplant Recipients-Is There a Need for Antibiotic Stewardship? J Clin Med. 2021 Dec 31;11(1):226. doi: 10.3390/jcm11010226.

  PMID: 35011966 BACKGROUND

• Tamargo CL, Kant S. Pathophysiology of Rejection in Kidney Transplantation. J Clin Med. 2023 Jun 19;12(12):4130. doi: 10.3390/jcm12124130.

  PMID: 37373823 BACKGROUND

• Ye J, Yao J, He F, Sun J, Zhao Z, Wang Y. Regulation of gut microbiota: a novel pretreatment for complications in patients who have undergone kidney transplantation. Front Cell Infect Microbiol. 2023 Jun 6;13:1169500. doi: 10.3389/fcimb.2023.1169500. eCollection 2023.

  PMID: 37346031 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Dysbiosis

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Umberto Baccarani, MD PhD

  Department of Medicine, University of Udine

  PRINCIPAL INVESTIGATOR

• Riccardo Pravisani, MD PhD

  Department of Medicine, University of Udine

  PRINCIPAL INVESTIGATOR

• Patrizia Tulissi, MD

  Azienda Sanitaria Universitaria Friuli Centrale

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD PhD FEBS

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: February 13, 2025
• Study Start: November 15, 2024
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): April 15, 2028
• Last Updated: February 13, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)