Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft

NCT ID: NCT02179229

Last Updated: 2014-07-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2015-08-31

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.

Conditions

Renal Insufficiency, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

CONTROL

Patient in the CONTROL arm will receive a powder containing only tapioca-resistant starch comparable in colour, texture and taste to the synbiotic.

Group Type: PLACEBO_COMPARATOR

CONTROL

Intervention Type: DIETARY_SUPPLEMENT

Placebo will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.

SYNBIOTIC

Patients in this group will receive Probinul neutro® a synbiotic preparation containing (perpacket): lyophilised bacteria (5×109 Lactobacillus plantarum, 2×109 Lactobacillus casei subsp. rhamnosus and 2×109 Lactobacillus gasseri, 1×109 Bifidobacterium infantis and 1×109 Bifidobacterium longum, 1×109 Lactobacillus acidophilus, 1×109 Lactobacillus salivarius and 1×109 Lactobacillus sporogenes and 5×109 Streptococcus thermophilus), prebiotic inulin (2.2 g; VB Beneo Synergy 1) and 1.3 g of tapioca-resistant starch.

Group Type: EXPERIMENTAL

SYNBIOTIC

Intervention Type: DIETARY_SUPPLEMENT

Probinul Neutro® will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.

Interventions

CONTROL

Placebo will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.

Intervention Type: DIETARY_SUPPLEMENT

SYNBIOTIC

Probinul Neutro® will be taken at home for four weeks as 5 g powder packets to be dissolved in water three times a day far from meals.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

PLACEBO; Probinul Neutro®

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

Bruna Guida

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruna Guida, MD

Role: PRINCIPAL_INVESTIGATOR

Federico II University of Naples

Locations

Nutrition Unit of the Federico II University of Naples

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Bruna Guida, MD

Role: primary

bguida@unina.it

0039-081-7462102

Rossella Trio, BSci

Role: backup

rostrio@unina.it

References

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.

Reference Type: DERIVED

PMID: 36126902 (View on PubMed)

Other Identifiers

Syn-Graft Study

Identifier Type: -

Identifier Source: org_study_id