Randomized Controlled Trial
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2022; 28(46): 6573-6588
Published online Dec 14, 2022. doi: 10.3748/wjg.v28.i46.6573
Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea: Randomized controlled trial
Karolina Anderle, Michael Wolzt, Gabriele Moser, Bettina Keip, Johannes Peter, Claudia Meisslitzer, Ghazaleh Gouya, Michael Freissmuth, Cornelius Tschegg
Karolina Anderle, Michael Wolzt, Department of Clinical Pharmacology, Medical University of Vienna, Vienna 1090, Austria
Gabriele Moser, Bettina Keip, Johannes Peter, Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1090, Austria
Claudia Meisslitzer, Cornelius Tschegg, Glock Health, Science and Research GmbH, Deutsch-Wagram 2232, Lower Austria, Austria
Ghazaleh Gouya, Gouya Insights, Vienna 1010, Austria
Michael Freissmuth, Institute of Pharmacology and the Gaston H. Glock Research Laboratories for Exploratory Drug Development, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna 1090, Austria
Author contributions: Wolzt M, Moser G, Meisslitzer C, Gouya G and Tschegg C conceptualized the study; Wolzt M, Meisslitzer C, Gouya G, Freissmuth M and Tschegg C designed the methodology; Anderle K, Wolzt M, Moser G, Keip B and Peter J performed the investigation; Anderle K, Wolzt M, Moser G, Keip B, Peter J, Meisslitzer C, Gouya G, Freissmuth M and Tschegg C performed the data curation and reviewed/edited the manuscript for important intellectual content; Gouya G performed the formal analysis of data; Moser G and Freissmuth M performed the data validation; Anderle K wrote the original draft of the manuscript; Wolzt M and Tschegg C provided resources; Keip B and Peter J provided software; Anderle K, Meisslitzer C, Gouya G and Tschegg C performed project administration; Tschegg C and Meisslitzer C were responsible for funding acquisition; Wolzt M and Gouya G performed study supervision; All authors had access to the study data and reviewed and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Medical University of Vienna (No. 1295/2019), Ethics Committee of Upper Austria (No. 1208/2019) and the Austrian Federal Office for Safety in Health Care (BASG).
Clinical trial registration statement: This study was registered at ClinicalTrials.gov registry (Identifier NCT04138186).
Informed consent statement: All study participants provided verbal and written informed consent prior to study inclusion.
Conflict-of-interest statement: The Medical University of Vienna and Klinikum Wels-Grieskirchen were reimbursed for all trial-related work hours, material and effort spent by the study sponsor. Investigators or study staff did not receive any payment. Michael Freissmuth is the recipient of an unrestricted research endowment by G.H. Glock.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Michael Wolzt, MD, Professor, Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria. michael.wolzt@meduniwien.ac.at
Received: June 27, 2022
Peer-review started: June 27, 2022
First decision: August 19, 2022
Revised: September 9, 2022
Accepted: November 16, 2022
Article in press: November 16, 2022
Published online: December 14, 2022
Processing time: 163 Days and 22.1 Hours
Abstract
BACKGROUND

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder with poor response to treatment. IBS with predominant diarrhea (IBS-D) is accompanied by abdominal pain as well as high stool frequency and urgency. Purified clinoptilolite-tuff (PCT), which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®, has previously shown therapeutic potential in other indications based on its physical adsorption capacity.

AIM

To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT.

METHODS

In this randomized, placebo-controlled, double-blind pilot study, 30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled. Following a 4-wk run-in phase, 14 patients were randomized to receive a 12-wk treatment with G-PUR® (2 g three times daily), and 16 patients received placebo. The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject’s Global Assessment (SGA) of Relief was assessed as the primary outcome. For the secondary outcomes, validated IBS-D associated symptom questionnaires, exploratory biomarkers and microbiome data were collected.

RESULTS

The proportions of SGA of Relief responders after 12 wk were comparable in both groups, namely 21% in the G-PUR® group and 25% in the placebo group. After 4 wk of treatment, 36% of patients in the G-PUR® group vs 0% in the placebo group reported complete or considerable relief. An improvement in daily abdominal pain was noted in 94% vs 83% (P = 0.0353), and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR® and placebo groups, respectively. Positive trends were observed for 50% of responders in the Bristol Stool Form Scale. Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score. Only 64% in the G-PUR® group compared to 86% in the placebo group required rescue medication intake during the study. Stool microbiome studies showed a minor increase in diversity in the G-PUR® group but not in the placebo group. No PCT-related serious adverse events were reported.

CONCLUSION

In this randomized, double-blind, placebo-controlled study, the PCT product, G-PUR®, demonstrated safety and clinical benefit towards some symptoms of IBS-D, representing a promising novel treatment option for these patients.

Keywords: Irritable bowel syndrome; Diarrhea; Functional gastrointestinal disorder; Clinoptilolite; Zeolite; Treatment

Core Tip: The purified clinoptilolite-tuff (PCT) product, G-PUR®, provided improvement in abdominal symptoms and stool abnormalities in patients with irritable bowel syndrome (IBS) with predominant diarrhea. Additionally, it reduced the use of rescue medication and tended to enrich gut microbiome diversity compared to placebo, while showing no safety concerns. Hence, the PCT product, G-PUR®, represents a promising novel treatment option for patients with IBS with predominant diarrhea.