For decades, advancements in treating children with short bowel syndrome were incremental and limited to improving the delivery of parenteral nutrition (PN). Now, a groundbreaking study suggests a strategy that may significantly improve gut function and reduce the need for PN.

Cincinnati Children’s was the lead site for this open-label, multisite study. The pediatric subjects received a daily injection of teduglutide, an analog of glucagon-like peptide 2 (GLP2), for 12 weeks. The analog was found to improve intestinal rehabilitation by promoting mucosal growth and possibly by restoring gastric emptying and secretion, thereby reducing intestinal losses and promoting intestinal absorption.

Substantial improvement 
“This is the first significant advance we’ve seen in the treatment of short bowel syndrome in 50 years, in that the therapy actually improves the structural and functional integrity of the intestine,” says Samuel Kocoshis, MD, a pediatric gastroenterologist at Cincinnati Children’s and senior author of the study. “Patients showed substantial improvement in gut function with a reduction in PN requirement of about 40 percent. Four of the 37 subjects were able to discontinue PN entirely after the 12-week study.”

Researchers have studied several other hormones hoping to see similar results, but teduglutide offers the greatest potential because it can improve intestinal function and cell proliferation in the gut almost immediately, according to Conrad Cole, MD, MPH, MSc, a pediatric gastroenterologist at Cincinnati Children’s and co-principal investigator of the study. “Naturally occurring GLP2 is not practical because of a short half-life,” Cole adds. “The analog, with just a single amino acid substitution, has a half-life of several hours, so it can be given subcutaneously and is likely to be effective for a longer period of time.”

Follow-up study
The study, “Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome,” was published in the Journal of Pediatrics in February 2017. Patients were enrolled sequentially into three teduglutide cohorts or received standard of care; of the three doses studied, only the two larger doses were effective. After reviewing the results, the Food and Drug Administration requested a follow-up study that involved testing the efficacy and safety of the larger doses and providing follow-up after teduglutide therapy is discontinued. Results from that 24-week study will be available in 2018.

These and other clinical research trials take place within the Intestinal Rehabilitation and Intestinal Transplant Programs at Cincinnati Children’s, where pediatric subspecialists provide comprehensive, multidisciplinary care for children with complex intestinal disorders leading to short bowel syndrome and intestinal failure. The clinical teams have a reputation for innovation and evidence-based treatment protocols, resulting in strong outcomes that include a central line-associated bloodstream infection rate that is consistently below 1.6 days per 1,000 catheter days. The program also emphasizes the use of lipid-sparing protocols and the compassionate use of IV fish-oil-based lipids in a select group of patients. The vast majority of their patients on chronic PN have a direct bilirubin level of less than 2 mg/dl.

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