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

Renal Insufficiency, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02179229
• Other study ID #: Syn-Graft Study
• Status: Recruiting
• Phase: N/A
• First received: June 27, 2014
• Last updated: July 1, 2014
• Start date: June 2014
• Est. completion date: August 2015

Study information

• Verified date: June 2014
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Nutrition Unit of the Federico II University of Naples	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No