Effect of the Synbiotic Probinul-Neutro® on Gastrointestinal Symptoms and Plasma p-Cresol Level in Chronic Renal Failure

EFFECT OF SHORT-TERM TREATMENT WITH THE SYNBIOTIC PROBINUL-NEUTRO® ON GASTROINTESTINAL SYMPTOMS AND CIRCULATING PLASMA p-CRESOL LEVEL IN PATIENTS WITH CHRONIC RENAL FAILURE: A RANDOMIZED DOUBLE BLIND PILOT STUDY.

The interest on gastrointestinal (GI) dysfunction in CKD has been growing in the last years. it is now accepted that GI dysfunction in dialyzed patients may contribute to systemic microinflammation by promoting gut dysbiosis and bacterial translocation in the blood. Another mechanism by which GI dysfunction contributes to systemic symptoms in CKD is related to metabolic activity of the dysbiotic microflora growing in the gut of these patients to generate toxic compounds such as phenols, indoles, and amines. Epidemiological evidence has strongly linked one of these compounds, p-Cresol, to cardiovascular risk and mortality in CKD. In the present paper the investigators investigated the effect of a probiotic/prebiotic mixture on plasma p-cresol concentrations and GI symptoms and in CKD patients not on dialysis yet.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: SYNBIOTIC

Detailed Description

In patients with chronic kidney disease (CKD), alterations in gut microbioma are posited to be responsible for gastrointestinal symptoms and generation of p-cresol, a uremic toxin, that has been associated to CKD progression and cardiovascular mortality.

This double blind randomized placebo controlled pilot study evaluates whether Probinul-neutro®, a synbiotic preparation that normalizes intestinal microflora, may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients.

Thirty patients on III-IV CKD stages were randomized to receive either Probinul neutro® or placebo for four weeks. Total plasma p-cresol concentrations was assessed at baseline, and 15 and 30 days after treatment start. At the same study times, ease and frequency of defecation, upper and lower abdominal pain, stool shape, borborygmi and flatus were quantified by subjective assessment questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80129
    • Federico II University of Naples

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age >18 years
• eGFR between 20 and 60 mL/min (stage 3-4 CKD, according to the K/DOQI CKD classification)

Exclusion Criteria:

• severe infections
• diabetes
• malignancy
• history of food intolerance
• autoimmune disorders
• severe malnutrition
• clinical conditions requiring artificial feeding
• kidney transplant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SYNBIOTIC; Patients of this group assumed Probinul-Neutro® po 5g three times a day for 30 days	Dietary supplement: SYNBIOTIC; INTERVENTION: Probinul neutro® assumed three times a day far from meals as 5 g powder packets dissolved in water. Probinul neutro® contains 5×109 Lactobacillus plantarum, 2×109 Lactobacillus casei subp. rhamnosus and 2×109 Lactobacillus gasseri, 1×109 Bifidobacterium infantis and 1×109 Bifidobacterium longum, 1×109 Lactobacillus acidophilus, 1×109 Lactobacillus salivarus and 1×109 Lactobacillus sporogenes and 5×109 Streptococcus termophilus, prebiotic inulin (2.2 g; VB Beneo Synergy 1) and 1.3 g of tapioca-resistant starch. PLACEBO: Tapioca-resistant starch powder similar in colour, texture and taste to the symbiotic mixture, assumed three times a day far from meals as 5 g powder packets dissolved in water.; Other Names: Probinul-Neutro® or PLACEBO
PLACEBO_COMPARATOR: PLACEBO; patients of this group received 5g of placebo 3 times a day for 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in plasma p-cresol concentration	Fasting blood samples were drawn for the p-cresol plasma level	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite outcome of gastrointestinal symptoms	Patients were asked to fill in a form for the scored evaluation of gastrointestinal symptoms (upper and inferior abdominal pain, borborygmus and flatus defecation frequency or easeand stool), and stool shape (Bristol stool chart)	30 days

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Guida B, Germano R, Trio R, Russo D, Memoli B, Grumetto L, Barbato F, Cataldi M. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. Nutr Metab Cardiovasc Dis. 2014 Sep;24(9):1043-9. doi: 10.1016/j.numecd.2014.04.007. Epub 2014 May 2.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (ESTIMATE): December 11, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 6, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: synbiotic; chronic kidney disease; p-cresol
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: Guida56