Purgative Meals for Colonoscopy Prep

By Jamie Santa Cruz

Researchers have developed a safe and effective alternative to the dreaded bowel prep currently used prior to colonoscopy.

Patients routinely complain that bowel preparation prior to a colonoscopy is a substantial turnoff, but a new alternative to traditional preparation methods has emerged on the horizon. Researchers from Dartmouth-Hitchcock Medical Center have developed laxative-infused meals that provide good-to-excellent bowel cleansing as well as good-to-excellent patient tolerability ratings, based on a small pilot study presented earlier this year at the Digestive Disease Week annual meeting.

Inadequate Screening: A Substantial Public Health Problem
"Any gastroenterologist will tell you that patients come in for their colonoscopies not dreading the procedure itself, but dreading the prep and hating the prep when they take it. It's really a miserable experience," says Corey Siegel, MD, MS, an associate professor of medicine at Dartmouth Medical School and director of the Inflammatory Bowel Disease Center at the Dartmouth-Hitchcock Medical Center.

The issue, Siegel says, is not merely one of solving individual patient dissatisfaction; public health is also at stake. Various medical organizations, including the American College of Gastroenterology,1 the American Cancer Society,2 and the US Preventive Services Task Force,3 recommend colonoscopies to screen for colorectal cancer every 10 years, beginning at the age of 50. Colorectal cancer is the third most common type of cancer for both men and women in the United States and is also the third leading cause of death from cancer,4 though the disease is highly treatable if caught early. Yet despite recommendations, screening rates remain low, and more than one-third of Americans aged 50 or older do not receive screening at the recommended intervals.4,5

"There are millions of people every year who aren't getting colonoscopies who really need them," Siegel says. "When those patients are surveyed and asked why [they] aren't coming in, the No. 1 reason is they don't want to take the prep."

But despite the substantial public health burden, there have been few attempts to improve the tolerability of screening, says Michael Allio, strategy advisor and head of the product development team at ColonaryConcepts, a new biotechnology company founded to commercialize the research. "There hasn't been a lot of innovation in this very widespread procedure in a long time. From our vantage point, it's ripe for disruptive innovation and putting the patient first."

Transformative Concept: Edible Colonoscopy Prep
To address the problem, the team at Dartmouth-Hitchcock has challenged the assumption that patients need to fast and then ingest a significant quantity of distasteful liquid prior to scoping. Instead, their solution is to use food to deliver the purgative and electrolytes required for bowel preparation. "Patients can eat, they don't have to fast, they enjoy the experience," Allio says.

In a phase 1 pilot trial conducted earlier this year, subjects were given a series of small meals containing the purgative polyethylene glycol (PEG-3350), which they ate throughout the day prior to the colonoscopy. The primary endpoints for the pilot study were safety and efficacy, as judged by the endoscopist's rating. Although the trial was originally intended to include 30 patients, the researchers stopped with 10 because the results were so positive. All 10 of the colonoscopies were deemed successful, with nine of the 10 patients judged to have "good" bowel preparation and the tenth judged as "excellent."

In comparing the efficacy of the purgative meals with standard bowel preparation methods, Allio notes that there are two ways to measure efficacy. The first examines whether or not the meals work functionally to prepare the bowel for scoping. On this measure, the group is not necessarily trying to produce bowel preparation superior to that achieved through current standard methods. "The framework for these first two phases of the clinical trials has been equivalency, not superiority," says Allio, adding that results to date suggest functional efficacy is comparable between the purgative meals and standard preparations.

A second measure of efficacy, however, is whether patients actually adhere to the preparation regimen. With standard bowel preparations, failure to complete the regimen is common because the distasteful liquids patients must drink frequently make them feel so sick they can't finish, Siegel says. Inadequate bowel preparation, in turn, compromises test results: upward of 20% of all colonoscopies in the United States have been reported to fail due to poor patient preparation or inability to view the colon clearly.6,7 On this measure, the team expects their product to prove dramatically superior. "We think more people will be able to finish our [prep] than a standard bowel prep," Siegel says. "Finishing the prep is huge."

The purgative meals could have a significant impact not only in the United States but also in other nations. According to Allio, the United States represents only about one-half of the world market for colonoscopies, and other nations struggle with low screening rates as well. "This is not just a US challenge; it's a global challenge," he says.

Upcoming Research and Development
Currently, the research team is engaged in a phase 2 trial, which began in May 2015 and will conclude later this fall. According to Allio, the primary endpoints for the phase 2 study, which is expected to include about 100 patients, are the same as in the pilot (safety and efficacy), but secondary endpoints include gathering input about patient preferences on menu options and about the experience in general. Polyethylene glycol remains the active ingredient in the meals in the phase 2 trial, but the research team is relying on a multidisciplinary development and design team of food scientists, culinary research chefs, and product designers to refine their menus and test new food and beverage forms.

To date, Siegel says, there are no known drawbacks to the purgative meals compared with standard bowel preparations. Of course, the available meals may not present a perfect match for every patient's tastes, he says, but most patients are simply grateful to have actual food to eat rather than having to fast. "Compared to what's currently available […], we are so far ahead from a patient-centeredness standpoint."

If the phase 2 trial proves successful, a phase 3 trial is expected in 2016, and the company is targeting a commercial launch sometime in 2018. According to Siegel, the commercial offering will be a complete kit containing everything patients need to complete the bowel preparation. All foods in the kit will be shelf stable and will include a series of small meals, bars, and shakes. And Siegel stresses the fact that the kits will include very clear instructions on exactly how to consume each item—a response to complaints in their patient surveys that currently available preparations lack clear directions.

"We hear [it] all the time—patients say there must be a better way," Siegel says. "We came up with a better way, and that better way works, it's effective, it's safe, and patients really love it. And it's going to be an incredible advancement for our field and for public health."

— Jamie Santa Cruz is a freelance writer based in Englewood, Colorado.

References
1. Rex DK, Johnson, DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi, JM. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol. 2009;104:739-750.

2. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58(3):130-160.

3. US Preventive Services Task Force. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(9):627-637.

4. Colorectal cancer facts & figures 2014-2016. American Cancer Society website. http://www.cancer.org/acs/groups/content/documents/document/acspc-042280.pdf

5. Centers for Disease Control and Prevention (CDC). Vital Signs: colorectal cancer screening test use — United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):881-888.

6. Lebwohl B, Wang TC, Neugut AI. Socioeconomic and other predictors of colonoscopy preparation quality. Dig Dis Sci. 2010;55(7):2014-2020.

7. Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest Endosc. 2003;58(1):76-79.