Sphincter of Oddi dysfunction (SOD) encompasses a spectrum of disorders in which dysfunction of the biliary and/or pancreatic sphincters result in abdominal pain. The diagnosis is often considered in patients with biliary-type pain who have previously undergone cholecystectomy. The Evaluating Predictors &Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial is a prospective, double-blind, randomized, sham-controlled multi-center trial with a maximum of 214 randomized subjects who have received a prior cholecystectomy and are diagnosed with the clinical syndrome of SOD (as defined by the Rome III criteria). Subjects will be selected with severe pain-related disability (Grade 3 or 4 on the RAPID instrument), with no objective signs of biliary or pancreatic disease (i.e. SOD type III). The overall goal is to assess the value of endoscopic sphincterotomy as a treatment for adult subjects categorized as SOD III suffering from pain after cholecystectomy. Success is defined as Grade 1 pain-related disability (little or no disability during a 90-day period) on the RAPID at 9 and 12 months post-procedure. Subjects and study team members will be blind to treatment assignment. A 2:1 randomization allocation in favor of sphincterotomy and stratified by results of sphincter manometry (SOM - abnormal/normal) and center will be used. The following secondary aims will be assessed: 1) evaluate the relationship between the results of SOM (abnormal/normal), and the primary outcome (success/failure);2) in the sub group of patients with manometrically proven PSH, evaluate the success rate of subjects who receive biliary sphincterotomy alone versus subjects who receive dual sphincterotomy;3) evaluate the effects of pre-specified clinical prognostic factors on the primary outcome;4) evaluate anxiety and depression scores over time and their relation to study outcomes;and 5) evaluate the economic impact of SOD III and endoscopic sphincterotomy in patients with SOD III. In addition, for a subset of eligible patients who decline randomization, a careful follow-up study (EPISOD2) of standard of care treatment will be conducted to assist in the interpretation and assessment of generalizability of the EPISOD primary aim as well as several of the secondary aims.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZDK1-GRB-7 (M3))
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Serrano, Jose
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Medical University of South Carolina
Internal Medicine/Medicine
Schools of Medicine
United States
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Cotton, Peter B (2018) Why did the sham-treated EPISOD study subjects do so well? Important lessons for research and practice. Gastrointest Endosc :
Small, Aaron J; Kozarek, Richard A (2015) Sphincter of Oddi Dysfunction. Gastrointest Endosc Clin N Am 25:749-63
Brawman-Mintzer, Olga; Durkalski, Valerie; Wu, Qi et al. (2014) Psychosocial characteristics and pain burden of patients with suspected sphincter of Oddi dysfunction in the EPISOD multicenter trial. Am J Gastroenterol 109:436-42
Cotton, Peter B; Durkalski, Valerie; Romagnuolo, Joseph et al. (2014) Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA 311:2101-9
Romagnuolo, Joseph; Cotton, Peter B; Durkalski, Valerie et al. (2014) Can patient and pain characteristics predict manometric sphincter of Oddi dysfunction in patients with clinically suspected sphincter of Oddi dysfunction? Gastrointest Endosc 79:765-72
Cotton, Peter B; Durkalski, Valerie; Orrell, Kyle B et al. (2010) Challenges in planning and initiating a randomized clinical study of sphincter of Oddi dysfunction. Gastrointest Endosc 72:986-91