Randomized Controlled Trial
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World J Gastroenterol. Sep 14, 2014; 20(34): 12301-12307
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.12301
Resolution of acute gastroenteritis symptoms in children and adults treated with a novel polyphenol-based prebiotic
Telma Noguera, Robert Wotring, Chris R Melville, Kara Hargraves, Jochen Kumm, John M Morton
Telma Noguera, Instituto Centroamericano de Investigación Clínica, Managua 050-008-4, Nicaragua
Robert Wotring, Chris R Melville, Kara Hargraves, Greenteaspoon Inc, Stanford, CA 94305, United States
Jochen Kumm, Department of Biology, Stanford University, Stanford, CA 94305, United States
John M Morton, Bariatric and Minimally Invasive Surgery, Stanford School of Medicine, Stanford, CA 94305, United States
Author contributions: Noguera T, Wotring R and Morton JM conceived and designed the study; Wotring R, Melville CR and Hargraves K performed the search of literature; Noguera T and Wotring R acquired the data; Kumm J, Morton JM and Wotring R analyzed and interpreted data; Wotring R, Melville CR and Hargraves K drafted the article; Morton JM, Noguera T and Kumm J revised for critical content; all authors reviewed the manuscript and approved it.
Correspondence to: John M Morton, MD, MPH, Chief of Bariatric and Minimally Invasive Surgery, Stanford School of Medicine, 300 Pasteur Drive, H3680, Stanford, CA 94305, United States. research@greenteaspoon.com
Telephone: +1-650-6445377 Fax: +1-650-6445377
Received: November 20, 2013
Revised: May 15, 2014
Accepted: June 12, 2014
Published online: September 14, 2014
Abstract

AIM: To test efficacy and durability of a polyphenol-based prebiotic treatment for acute gastroenteritis in a 300 patient double-blinded clinical study.

METHODS: A two-arm randomized, double-blinded, placebo-controlled clinical study was conducted at two public health centers in Managua, Nicaragua. Potential subjects who qualified based on inclusion and exclusion criteria were randomly assigned to one of two treatment arms. Two thirds of the subjects (n = 200) received a single titrated 0.5-2 ounce liquid dose of a novel polyphenol-based prebiotic (AlivaTM) diluted with 2 to eight ounces of oral rehydration solution (ORS). One third of the subjects (n = 100) were randomized to receive two liquid ounces of a taste and color-matched placebo diluted in eight ounces of ORS. The outcome variables measured included stool consistency, stomach discomfort, gas and bloating, and heartburn/indigestion. The study subjects ranked their stool consistency and the severity of their subjective symptoms at specified intervals from immediately prior to treatment, to five days post treatment. All subjects recorded their symptoms in a study diary. The study subjects also recorded the time and consistencies of all stools in their study diary. Stool consistency was compared to the picture and descriptions on the Bristol Stool Chart, and any stool rated greater than Type 4 was considered unformed. The clinical study team reviewed the study diaries with subjects during daily follow-up calls and close-out visits, and recorded the data in case report forms.

RESULTS: After receiving a single dose, Aliva treated subjects reported shorter median time to their last unformed stool (1 h 50 min) than placebo treated subjects (67 h 50 min.), a statistically significant difference [95%CI: -3178-(-2018), P = 0.000]. Aliva treated subjects also reported shorter median their time to last unformed stool (TTLUS) (1hrs 50 min) than placebo treated subjects (67 h 50 min), which was also a statistically significant difference (P = 0.000).The percentage of subjects recording TTLUS was greater for those who received Aliva vs placebo at 30 min (P = 0.027), 2 h (P = 0.000), 24 h (P = 0.000), 48 h (P = 0.000), 72 h (P = 0.000), and 5 d (P = 0.000) post dose. There were 146 study subjects 14 years old or older, which was the criteria set for reliable self-reporting of subjective symptoms. Of those 146 subjects, 142 reported stomach pain and discomfort during screening. From 90 minutes [95%CI: -1.8-(-0.01), P = 0.048] through 5 d [95%CI: -3.4-(-1.9), P = 0.000), the subjects treated with Aliva experienced significantly less stomach pain and discomfort than those who received placebo. Of those same 146 participants, 114 subjects reported gas and bloating during screening. Similarly, subjects who received Aliva experienced significantly less gas and bloating from 2 h [95%CI: -1.7-(-0.39), P = 0.030] through 5 d (95%CI: -2.0-0.42, P = 0.005) compared with the placebo arm.

CONCLUSION: In this double-blind, randomized clinical study, subjects with acute gastroenteritis receiving Aliva prebiotic showed significant and sustained improvement of multiple symptoms vs those receiving placebo.

Keywords: Prebiotic, Gastroenteritis, Diarrhea, Rotavirus, Infant Mortality, Dehydration, Heartburn, Polyphenol, Aliva, Greenteaspoon

Core tip: The global standard of care for treating acute gastroenteritis in children is 5-10 d of oral rehydration therapy, which saves lives and may reduce the duration of the illness by 20%. In this double-blind, placebo-controlled clinical study, 60% of subjects treated with a novel polyphenol-based prebiotic experienced their last unformed stool within 2 h vs 25% of the placebo treated subjects, and 89% within 24 h vs 38% of the placebo treated group. This represents a potentially extraordinary advance in the clinical management of acute gastroenteritis. If these results can be confirmed in additional studies with different populations, this treatment should become the new global standard of care.