Clinical trial NCT02179229: Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft
Official title: Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Renal Insufficiency, Chronic
Keywords: Kidney transplantation
pCresol
Immunosuppressant drugs
Lead sponsor: Federico II University
Sponsor class: OTHER
First posted: 2014-07-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish whether a short treatment with the synbiotic combination Probinul neutro® may decrease the plasma concentration of the uremic toxin p-cresol in patients bearing a kidney allograft. The effect of this treatment on plasma levels of immunosuppressant drugs will be evaluated as well.

Detailed description: Marked alterations in the gut microbiome take place in patients with chronic kidney disease (CKD) that show an overgrowth of aerobic bacteria such as Enterobacteriaceae, Halomonadaceae, Moraxellaceae, and Pseudomonadaceae and a decrease of anaerobic bacteria such as Lactobacillaceae and Prevotellaceae. These changes also occur after kidney transplantation. The dysbiotic microflora produces toxic compounds such as phenols, indoles, and amines that are absorbed through the intestinal mucosa and cause systemic toxicity. Compelling evidence showed the association of one of these compounds, p-cresol and of its main metabolite p-cresylsulfate, to cardiovascular risk and mortality in CKD. Therefore, new therapeutic strategies decreasing the generation or absorption of this uremic toxin are expected to have a favorable impact on the clinical course of the disease. In the present study, the effect of the synbiotic Probinul neutro® on p-cresol concentration in patients bearing a kidney allograft will be evaluated. Synbiotics are associations of prebiotics and probiotics. Probiotics are living microorganisms such as Bifidobacterium and Lactobacillus species that are administered to repopulate the gut with a "normal" microflora. Prebiotics are non-digestible food adjuncts that can be selectively fermented by probiotics or by normal intestinal microflora. In synbiotics the prebiotic and probiotic components synergize to restore the normal gut microflora. Indeed, the probiotic and prebiotic components of the synbiotic may both affect the gut microbiome through with different mechanisms. Probiotics contain bacteria that are part of the normal microbiome and are lowered in CKD such as anaerobes of Bifidobacterium sp. and facultative anaerobes of Lactobacillus sp. These bacterial species, unable to convert aromatic aminoacids into p-cresol, may replace by competition the p-cresol-producing bacteria of the dysbiotic microflora because of their ability to release substances toxic for the dysbiotic microflora such as the bacteriocins, and to activate innate and adaptive immunity. Prebiotics, instead, promote the growth of non-p-cresol producing commensal flora, including lactobacilli and bifidobacteria that selectively metabolize the oligosaccharides contained in prebiotic. The combined activity of pre- and probiotic is expected to reduce the production of p-cresol in the gut by decreasing the bacterial species generationg this compound. We recently showed that a short term treatment with Probinul neutro® causes, indeed, a decrease in p-cresol plasma levels in patients with satge III/IV CKD.

Eligibility criteria: Inclusion Criteria:

* Previous renal allograft transplantation

Exclusion Criteria:

* severe infections
* diabetes
* malignancy
* history of food intolerance
* autoimmune disorders
* severe malnutrition or clinical conditions requiring artificial feeding

Primary outcomes:
measure: Change in p-cresol plasma concentration
timeFrame: one month
Secondary outcomes:
measure: Change in bowel habits
timeFrame: one month
measure: Change in plasma immunosuppressant drug concentration
timeFrame: one month
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Nutrition Unit of the Federico II University of Naples
Study officials:
affiliation: Federico II University of Naples
name: Bruna Guida, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 20;9(9):CD014804. doi: 10.1002/14651858.CD014804.pub2.