Randomized Controlled Trial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2015; 21(18): 5685-5694
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5685
Oral mixture of autologous colon-extracted proteins for the Crohn’s disease: A double-blind trial
Eran Israeli, Ehud Zigmond, Gadi Lalazar, Athalia Klein, Nilla Hemed, Eran Goldin, Yaron Ilan
Eran Israeli, Ehud Zigmond, Gadi Lalazar, Athalia Klein, Nilla Hemed, Eran Goldin, Yaron Ilan, Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, IL-91120 Jerusalem, Israel
Author contributions: Israeli E, Zigmond E and Lalazar G exmianed the patients in the study; Klein A perfomred the antigen preparation; Hemed N contributed to study nurse; Goldin E and Ilan Y contributed to study design, management, and analysis of data.
Supported by (in part) grants from ENZO Biochem, New York City, NY, United States, and the Roaman-Epstein Liver Research Foundation (to Ilan Y).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yaron Ilan, MD, Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, POB 12000, IL-91120 Jerusalem, Israel. ilan@hadassah.org.il
Telephone: +972-2-6431021 Fax: +972-2-6777816
Received: August 1, 2014
Peer-review started: August 2, 2014
First decision: August 27, 2014
Revised: September 12, 2014
Accepted: November 30, 2014
Article in press: December 1, 2014
Published online: May 14, 2015
Processing time: 289 Days and 21.3 Hours
Abstract

AIM: To evaluate the safety and efficacy of oral administration of Alequel™, an autologous protein-containing colon extract.

METHODS: A total of 43 patients were enrolled in a randomized, placebo-controlled, double-blind trial. Patients were orally administered with autologous protein-containing colon extract three doses of autologous study drug per week for 15 wk, for a total of 45 doses. Patients were followed for safety parameters. Remission was defined as a Crohn’s disease activity index (CDAI) score of less than or equal to 150. All patients were followed for changes in subsets of T cells by fluorescence-activated cell sorting analysis.

RESULTS: Analysis was performed on a total number of evaluable patients of 14 in the study drug group and 15 in the placebo group. Treatment was well tolerated by all patients. No major treatment-related adverse events were reported or observed in any of the treated patients during the feeding or follow-up periods. Between weeks 6 and 9 of the study, six of the 14 (43%) evaluable subjects who received the study drug achieved a CDAI of 150 or lower. In contrast, five of the 15 (33%) evaluable subjects in the placebo group achieved remission. Between weeks 9 and 12, the remission rates were 50% and 33% for the drug group and placebo group, respectively. Among the drug-treated subjects who achieved remission, the effect of the drug was judged as stable in eight of the 14 subjects as measured by at least two CDAI scores indicating remission in the 15-wk treatment period. A decreased percentage of peripheral natural killer T regulatory cells (a decrease of 28% vs an increase of 16%) and an increased ratio of CD4+/CD8+ T lymphocytes (an increase of 11% vs a decrease of 9%) were noted in subjects with a significant clinical response.

CONCLUSION: Oral administration of the autologous colonic extract could be a safe and effective for the treatment of patients with moderate to severe Crohn’s disease.

Keywords: Oral tolerance; Crohn’s disease; Natural killer T cells; Immune modulation

Core tip: Oral administration of the autologous colonic extract could be a safe and effective for the treatment of patients with moderate to severe Crohn’s disease (CD). Increased ratio of CD4+/CD8+ T lymphocytes was noted in subjects with a significant clinical response and may serve as a biomarker for response to therapy.