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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02179229
Recruitment Status : Unknown
Verified June 2014 by Bruna Guida, Federico II University.
Recruitment status was:  Recruiting
First Posted : July 1, 2014
Last Update Posted : July 2, 2014
Information provided by (Responsible Party):
Bruna Guida, Federico II University

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.

Condition or disease Intervention/treatment Phase
Renal Insufficiency, Chronic Dietary Supplement: CONTROL Dietary Supplement: SYNBIOTIC Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Pre- and Probiotics on P-cresol Plasma Levels in Patients Bearing a Kidney Allograft
Study Start Date : June 2014
Estimated Primary Completion Date : June 2015
Estimated Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Cresol

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 Name: 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 Name: Probinul Neutro®

Primary Outcome Measures :
  1. Change in p-cresol plasma concentration [ Time Frame: one month ]
    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.

Secondary Outcome Measures :
  1. Change in bowel habits [ Time Frame: one month ]
    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

  2. Change in plasma immunosuppressant drug concentration [ Time Frame: one month ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02179229

Nutrition Unit of the Federico II University of Naples Recruiting
Naples, Italy, 80131
Contact: Bruna Guida, MD    0039-081-7462102   
Contact: Rossella Trio, BSci   
Principal Investigator: Bruna Guida, MD         
Sponsors and Collaborators
Federico II University
Principal Investigator: Bruna Guida, MD Federico II University of Naples

Responsible Party: Bruna Guida, M.D., Federico II University Identifier: NCT02179229     History of Changes
Other Study ID Numbers: Syn-Graft Study
First Posted: July 1, 2014    Key Record Dates
Last Update Posted: July 2, 2014
Last Verified: June 2014

Keywords provided by Bruna Guida, Federico II University:
Kidney transplantation
Immunosuppressant drugs

Additional relevant MeSH terms:
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases