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

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.

Study Overview

• Status: Unknown
• Conditions: Renal Insufficiency, Chronic
• Intervention / Treatment: Dietary supplement: CONTROL; Dietary supplement: SYNBIOTIC

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • Recruiting
    • Nutrition Unit of the Federico II University of Naples
    • Contact: Bruna Guida, MD; Phone Number: 0039-081-7462102; Email: bguida@unina.it
    • Contact: Rossella Trio, BSci; Email: rostrio@unina.it
    • Principal Investigator: Bruna Guida, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: CONTROL; Patient in the CONTROL arm will receive a powder containing only tapioca-resistant starch comparable in colour, texture and taste to the synbiotic.	Dietary supplement: 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.; Other Names: PLACEBO
EXPERIMENTAL: 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.	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.; Other Names: Probinul Neutro®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in p-cresol plasma concentration	Total p-cresol (free and glucurono- or sulpho-conjugates) plasma concentration will be assessed by reverse phase HPLC at baseline, 15 and 30 days after starting synbiotic treatment.	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bowel habits	Defecation frequency or ease, stool shape, upper or lower abdominal pain, frequency of borborygms or flatus will be assessed by asking the patients to fill a a form for the scored evaluation of GI symptoms and stool characteristics	one month
Change in plasma immunosuppressant drug concentration	Plasma concentration of the different immunosuppressant assumed by the patient (mycophenolate mofetil, cyclosporin, tacrolimus, everolimus or sirolimus) will be assessed at baseline, 15 and 30 days after the beginning of the study.	one month

Collaborators and Investigators

• Sponsor: Federico II University
• Investigators: Principal Investigator: Bruna Guida, MD, Federico II University of Naples

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ANTICIPATED): June 1, 2015
• Study Completion (ANTICIPATED): August 1, 2015

Study Registration Dates

• First Submitted: June 27, 2014
• First Submitted That Met QC Criteria: June 27, 2014
• First Posted (ESTIMATE): July 1, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 2, 2014
• Last Update Submitted That Met QC Criteria: July 1, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Kidney transplantation; pCresol; Immunosuppressant drugs
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: Syn-Graft Study