UPMC Children's Researchers Collaborate on FDA-Funded Study to Advance Pediatric Intestinal Failure Therapies

Simon Horslen, MD, MBChB, FRCPCH, director of Pediatric Hepatology at UPMC Children’s Hospital of Pittsburgh, along with Vikram Raghu, MD, MS, a colleague in the Division of Pediatric Gastroenterology, and Yaron Avitzur, MD, from Toronto SickKids Hospital, have been awarded an R01 grant from the U.S. Food and Drug Administration to advance research into pediatric intestinal failure (IF).

Their project is called “Defining Pediatric Intestinal Failure Natural History,” and its goals are to develop a better understanding of the natural history of the two general classifications of IF – short-bowel syndrome IF and functional IF – and lay the foundation for developing novel therapeutics to treat this rare disorder.

Project Details

Pediatric IF, is a rare and life-threatening condition. About 25,000 children in the U.S. have the disorder and there are approximately 1,300 new diagnoses each year. Because of the relative rarity of IF in pediatric patients, there is much that is still unknown about the natural history of disease, and there are few if any efficacious treatment options available outside of intestinal transplants for which not all patients are candidates.

Intestinal failure, which often necessitates lifelong dependence on parenteral nutrition, significantly affects patients' quality of life, growth, and development. IF carries with it high rates of morbidity and mortality. The new research project aims to address the current gaps in the natural history data of the condition, laying the groundwork for innovative therapies and improving clinical trial design for future interventions.

The research team will use the current International Intestinal Failure Registry (IIFR), which has enrolled so far close to 400 children living with IF since it was initiated. By auditing and expanding the registry's data, the new study seeks to refine our understanding of the condition's progression and likely trajectories, integrate patient-reported outcomes measures, and develop a machine learning-based classification system that can help stratify risk and guide therapy options for patients.

“This work will provide a much-needed foundation for advancing care in pediatric intestinal failure,” says Dr. Horslen. “By combining high-quality longitudinal data with patient and family perspectives, we can help to ensure that future therapies are both effective and meaningful to those living with this challenging condition.”

The integration of community-derived outcomes and novel analytic methods represents an evolution in how clinicians and researchers approach rare diseases like intestinal failure.

“Our goal is to create a robust framework that accelerates therapeutic development and improves survival and quality of life for our patients,” says Dr. Raghu.

This initiative is expected to impact care for children with both short bowel syndrome-associated intestinal failure and functional intestinal failure. The findings from the research will help to inform and shape current therapeutic approaches and standards of care but also facilitate the development of new, targeted treatments that address the clinical outcomes and quality-of-life measures important to patients and their families.

Reference

Defining Pediatric Intestinal Failure Natural History. NIH Project Number: R01F2007597. Contact PI: Simon Horslen.