Randomized Clinical Trial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2017; 23(48): 8615-8625
Published online Dec 28, 2017. doi: 10.3748/wjg.v23.i48.8615
Multicenter, randomized study to optimize bowel preparation for colon capsule endoscopy
David Kastenberg, Wilmot C Burch Jr, David P Romeo, Pankaj K Kashyap, David C Pound, Neophytos Papageorgiou, Ignacio Fernández-Urien Sainz, Carly E Sokach, Douglas K Rex
David Kastenberg, Division of Gastroenterology, Thomas Jefferson University, Philadelphia, PA 19107, United States
Wilmot C Burch Jr, Franklin Gastroenterology, PLLC, Franklin, TN 37067, United States
David P Romeo, Dayton Gastroenterology, Inc., Beavercreek, OH 45540, United States
Pankaj K Kashyap, Pinnacle Research Group LLC, Anniston, AL 36207, United States
David C Pound, Indianapolis Gastroenterology and Hepatology, Indianapolis, IN 46237, United States
Neophytos Papageorgiou, Department of Gastroenterology, American Medical Center, Nicosia 1311, Cyprus
Ignacio Fernández-Urien Sainz, Department of Gastroenterology, Servicio de Digestivo, Hospital de Navarra, Pamplona 31001, Spain
Carly E Sokach, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107, United States
Douglas K Rex, Indiana University Hospital, Indianapolis, IN 19107, United States
Author contributions: Rex DK contributed to conception and design of the study; Kastenberg D, Burch WC, Romeo DP, Kashyap PK, Pound DC, Papageorgiou NP, Fernández-Urien Sainz I and Rex DK acquired the data; Kastenberg D and Rex DK contributed to analysis and interpretation of the data; Kastenberg D and Sokach CE drafted the article; Kastenberg D critically revised the article for important intellectual content; all authors approved the final article.
Institutional review board statement: Each center obtained IRB approval prior to study initiation from the respective IRB or Research Ethics Committee.
Clinical trial registration statement: This study and protocol was registered with clinicaltrials.gov (ID# NCT02481219)
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Kastenberg D, reports grants and advisory board fees from Ferring, outside the submitted work. Burch WC, Romeo PD, Kashyap PK, Pound DC, and Sokach CE, do not declare any conflict of interests. Fernández-Urien Sainz I, reports personal fees from Medtronic, during the conduct of the study; personal fees from Medtronic, outside the submitted work. Papageorgiou NP, reports personal fees from Medtronic, during the conduct of the study; personal fees from Medtronic, outside the submitted work. Rex DK, reports other from Medtronic, during the conduct of the study; other from Medtronic, outside the submitted work; and Consulting fees, Olympus hororaria; Boston Scientific Research support; Endochoice; Endo Aid, Modivators, Boston Scientific.
Data sharing statement: All of the individual participant data collected during the trial, after de-identification, is available at www.clinicaltrials.gov (NCT 02481219) and will be accessible to anyone who wishes to access the data for any purpose.
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: David Kastenberg, FACP, MD, Professor, Division of Gastroenterology and Hepatology, Thomas Jefferson University, 4th Floor Main Building, 132 South 10th St. Philadelphia, PA 19107, United States. david.kastenberg@jefferson.edu
Telephone: +1-215-9558900 Fax: +1-215-9555513
Received: September 1, 2017
Peer-review started: September 3, 2017
First decision: September 13, 2017
Revised: September 29, 2017
Accepted: November 21, 2017
Article in press: November 21, 2017
Published online: December 28, 2017
Processing time: 117 Days and 8.3 Hours
ARTICLE HIGHLIGHTS
Research background

The technical performance of colon capsule endoscopy (CCE) has made great strides, but this technology remains highly dependent on the purgative procedure. The ideal capsule preparation would (1) adequately cleanse the colon; (2) propel the capsule through the GI tract within its battery life; (3) enable sufficient dwell time within the colon for accurate visualization; (4) be tolerable and safe; (5) be easily generalizable for the vast majority of patients. Each of these areas require improvement, and this study’s significance is that it moves this field forward by evaluating a new boost agent.

Research motivation

Tailoring the preparation procedure based on patient characteristics and real-time capsule feedback (“personalized” medicine) will likely improve CCE performance, tolerability, safety, and subsequently acceptance. Technological advancements that reliably visualize mucosa obscured by debris, and assist in the detection of polyps, would be immensely helpful as well.

Research objectives

The main objective was to evaluate the efficacy of new boost agent consisting of low dose sulfate solution combined with diatrizoate solution (“Study” regimen), and comparing this to low dose sulfate solution alone (“Control” regimen). We found that colon cleansing was similar between the two regimens, but CCE completion and the proportion of subjects in which the capsule passed through the colon in less than 40 min were significantly greater with the Study regimen. Also observed was numerically greater, not statistically superior, polyp detection with the Study regimen. This suggests that it is reasonable to incorporate the boost regimen of low dose sulfate solution and diatrizoate solution into the preparation procedure for CCE.

Research methods

This was a multicenter, prospective, randomized, controlled study comparing two preparation regimens for CCE at six United States sites, 2 of which were academic centers. CCE studies were read centrally by experienced readers who were blinded to subject randomization, and a validated cleansing scale for CCE was utilized.

Research results

The study regimen did not result in superior colon cleansing, but did result in a superior rate of CCE completion and higher proportion of studies with colonic transit less than 40 min. Increased polyp detection, though not significant, was observed in the Study arm suggesting that polyp detection was not compromised in this group. However, this study was not powered for polyp detection. We also observed a greater incidence of adverse events, primarily GI, in the Study group. This observation in the Study group did not appear to be related to the boost agent. Progress needs to be made in further improving the efficacy of colon cleansing, with the goal for CCE being more closely aligned with that established for traditional colonoscopy. Further, simplifying the regimen, shortening overall GI transit time, and lessening the incidence of adverse events related to the preparation regimen are all worthy of further study.

Research conclusions

Diatrizoate solution augments the performance of sulfate solution to create an effective and very low dose hyperosmotic boost agent for CCE. The combination of low dose sulfate solution and diatrizoate solution was superior to low dose sulfate solution alone with respect to CCE completion and the frequency that the capsule traversed the colon in less than 40 minutes. These findings, along with a trend toward higher polyp detection with the combination Study regimen, support the use of low dose sulfate solution combined with diatrizoate solution as a boost agent in place of low dose sulfate solution alone.

Research perspectives

While our findings represent an improvement in the preparation regimen for CCE, there is still much progress to be made in this arena. In particular, the rate of preparation adequacy needs to increase. Personalized medicine may play a role in optimizing the regimen for CCE. Using patient characteristics and real time capsule data, individual adjustments might include varying the volume of PEG-ELS, utilizing additional agents, adjusting the frequency and timing of medication administration, and more.