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PRObiotics for KIdney Transplantation (ProKiT)

U

University Hospital, Udine, Italy

Status

Invitation-only

Conditions

Dysbiosis
Urinary Tract Infections
Kidney Transplant Infection
Kidney Transplant Rejection

Treatments

Dietary Supplement: OMNi-BiOTiC® 41167
Dietary Supplement: Placebo

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT06825117
64/2024

Details and patient eligibility

About

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

Full description

Background

Urinary tract infections (UTI) and graft rejection in kidney transplanted (KT) patients are currently the most frequent complications in the short-term, with a reported incidence of 17-51% and 6- 11% within the first year, respectively. The pathogenesis of such complications is tightly related and is determined by multifactorial mechanisms. Recent studies have shown that gut microbiota may have a crucial role in the pathogenesis of both post-KT UTI and graft rejection. Following transplantation, KT recipients show measurable alterations in microbial diversity, composition and function, and such gut dysbiosis may not only favor the proliferation of pathogens but also modify the immuno-inflammatory profile of recipients, inducing a pro- inflammatory state. Moreover, gut microbiota does metabolize immunosuppressant drugs, variably modifying their pharmacokinetic characteristics. A significant correlation between gut microbiota species and urine microbial isolates in a context of UTI have been consistently identified, and certain microbiota profiles have been alternatively associated with graft immune tolerance and graft rejection episodes. According to the International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statements, probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.

Recent studies have shown that probiotic supplementation in KT recipients may variably improve kidney function in patients with chronic kidney disease as well as induce graft tolerance and decrease the risk of recurrent Clostridioides difficile infection. However, the evidence of possible beneficial effects of probiotics, including on UTI incidence in KT patients is missing.

Protocol

All Adult, Caucasian patients treated with kidney transplantation (KT) at SOC Clinica Chirurgica, ASUFC, Udine, Italy, from September 2024, and with an uneventful course during the first postoperative month (POM) will be evaluated for enrollment. Written informed consent to take part in the study will be obtained from each participant after being informed on study design, aims and potential adverse events.

The 132 subjects will be randomly allocated to either the probiotic arm or the placebo arm (control group). Group allocation will be double-blind. A computer random number algorithm (1:1 allocation ratio) will randomize participants, using blocks of four.

In the intervention group, patients will receive two sachets daily of OMNi-BiOTiC® 41167 for 6 months, while the control group will receive an equal amount of similar looking and tasting placebo.

Both study groups will remain on their standard diet and drug regimen during the study period. Adherence to therapy will be measured by sachet count.

The post-transplant clinical surveillance will follow the routine follow-up schedule for KT patients at the Department of Nephrology, ASUFC, Udine, Italy.

At enrollment (POM 1, visit 1) patients will be assessed with routine physical examination, clinical interview, blood exams, tacrolimus dosage and plasma concentration, Torque Teno Virus (TTV) and Acellular Growth Retardation Assay (AGRA) tests, urine tests, urine culture; Nova Food Frequency Questionnaires (NFFQ), Acute Cystitis Symptom Score (ACSS), Gastrointestinal Symptom Rating Scale, Irritable Bowel Syndrome version (GSRS-IBS, AstraZeneca R&D, SE-431 83 Mölndal, Sweden.) and quality of life SF-12 (Hogrefe Verlag, Göttingen, Germany) questionnaires will be administered; clinical data and laboratory data will be collected and saved in dedicated database; urine and stool samples will be collected and stored for microbiota determination; study product will be provided.

BK virus surveillance according to the routine follow-up schedule will be based on viral load measurement in blood and urine samples at POM 1, 3 and 6.

During the treatment period (POM1-POM7, visits 2-15) patients will be assessed with physical examination, routine blood exams, tacrolimus dosage and plasma concentration, urine tests, urine culture; ACSS, GSRS-IBS and SF-12 questionnaires will be administered; clinical data and laboratory data will be collected and saved in dedicated database. Study products will be provided regularly every fourth week.

At the end of the treatment (POM7, visit 16) patients will be assessed with physical examination, routine blood exams, tacrolimus dosage and plasma concentration, TTV and AGRA tests, urine tests, urine culture; NFFQ, ACSS, GSRS-IBS and SF-12 questionnaires will be administered; clinical data and laboratory data will be collected and saved in dedicated database; urine and stool samples will be collected and stored for microbiota determination.

Adverse events and serious adverse events will be evaluated at every visit.

Enrollment

132 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Trial design

Primary purpose

Prevention

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

132 participants in 2 patient groups, including a placebo group

Probiotic group
Experimental group
Treatment:
Dietary Supplement: OMNi-BiOTiC® 41167
Placebo group
Placebo Comparator group
Treatment:
Dietary Supplement: Placebo

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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