Evaluating Predictors & Interventions in Sphincter of Oddi Dysfunction

Study Overview
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Brief Summary
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The Evaluating Predictors & Interventions in Sphincter of Oddi Dysfunction(SOD) study (EPISOD) is a randomized sham-controlled study of biliary and pancreatic sphincterotomy as treatment for patients with pain after cholecystectomy fitting the criteria for sphincter of Oddi dysfunction type III.

Detailed Description
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Clinical Trial Phase: Phase III Study Sites Seven clinical centers in US Study Period Planned enrollment period - 3 years Planned duration of the study - 5 years Study Population SOD III Patients Primary Study Objective: To ascertain whether subjects with SOD III respond to sphincterotomy, Secondary Study Objectives To evaluate: the association between the results of Sphincter of Oddi Manometry (SOM) (abnormal/normal) and the primary outcome (success/failure); the success rate (as defined in the primary) of subjects who receive biliary sphincterotomy alone versus subjects who receive both biliary and pancreatic sphincterotomy in the subgroup of patients with manometrically proven hypertension of the pancreatic sphincter; the effects of pre-specified prognostic factors on the primary outcome; anxiety and depression scores over time and their relation to study outcomes; the economic impact of SOD III, and of endoscopic sphincterotomy in patients with SOD III; and, to, conduct a careful follow-up study (EPISOD2) of standard of care treatment (separate protocol). Study Design The EPISOD Trial is a parallel, randomized, double-blinded, sham-controlled, multicenter Phase III clinical trial of endoscopic sphincterotomy as treatment for adults 18 to 65 years of age diagnosed with SOD III. Sample Size A minimum of 214 subjects will be randomized using a 2:1 allocation in favor of sphincterotomy and will be followed for 12 months post-randomization.

Official Title
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A Phase III Randomized Multicenter Clinical Trial of Sphincterotomy for the Treatment of SOD III Patients

Conditions
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Sphincter of Oddi Dysfunction

Intervention / Treatment
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* Procedure: ERCP with sphincterotomy
* Procedure: ERCP without sphincterotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with the clinical syndrome of SOD, as defined by the Modified Functional Biliary Disorders Module of the Rome III criteria Pain burden of Grade 3 or higher on RAPID Questionnaire. Cholecystectomy more than 90 days before enrollment. Laboratory Tests: Results of blood tests taken within 1 week preceding the baseline visit and any others available from the preceding 6 months (post-cholecystectomy):Direct bilirubin, alkaline phosphatase, amylase and lipase results must be no greater than 2 X the upper level of normal.Transaminase levels can be no more than 3 X upper limit of normal. If the transaminases are elevated (<2X ULN) in association with a pain attack, they cannot have returned to normal within 3 days. Normal abdominal imaging by CT or MR/MRCP with bile duct reported at ≤9mm. Upper endoscopy examination without findings to explain the pain. Pain persisting despite a one trial of acid suppressant medications for one month (if tolerated). Pain persisting despite a trial of antispasmodics. Subjects on antidepressants for pain control (not required) should be taking them for a minimum of one month prior to the baseline assessment. 9.Patients with SOD with depressive and/or anxiety disorders who receive psychopharmacologic treatment must be on stable medication dose for at least 6 weeks. 10.Access to a telephone. 11.Must be able to speak, read, and write English. 12.Signed and dated informed consent. Exclusion Criteria: Prior ERCP treatment. Age < 18 or Age > 65. Pregnancy: Women who are pregnant at the time of Screening* will be excluded from the study. (*Note: Women who become pregnant AFTER the Baseline Visit/ERCP will be allowed to remain in the study for telephone follow-up visits). Prior gastric resection or surgery involving biliary diversion. Prior diagnosis of acute pancreatitis (lipase >3 x ULN) including post-ERCP pancreatitis, or of chronic pancreatitis by radiological imaging, EUS 5 or more criteria, or Cambridge criteria moderate or more on ERCP. Daily use of prescription analgesics over the previous month. Abdominal discomfort every day for the past month at level of 3 or more on a scale of 1-10. Presence of significant psychiatric disorders: Lifetime psychotic disorders, bipolar disorder; Substance use disorders within 6 months; Eating disorders within 2 years Moderate & severe depression defined by BDI-II (Beck Depression Inventory) cutoff scores >22 (unless receiving stable psychiatric therapy for six weeks); and/or, Suicidal risk (equal to or greater than low) using MINI suicide section or a score of greater than 0 on question 9 of the BDI. The total number of days in the previous 3 months that the subject has taken prescription analgesics due to episodes of abdominal pain is greater than the total number of days the subject had episodes of abdominal pain. Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation. ERCP Criteria: Pancreas divisum (complete or partial) (known or discovered at study ERCP). Any pathology found at ERCP (except sphincter hypertension). Failed pancreatic manometry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1.ERCP with sphincterotomy<br>ERCP with sphincterotomy: cutting the biliary sphincter muscle (sphincterotomy) | Procedure: ERCP with sphincterotomy<br>* cutting the biliary sphincter muscle (sphincterotomy)<br>|
| Placebo Comparator: 2.ERCP without sphincterotomy<br>ERCP without cutting the biliary sphincter muscle (sphincterotomy) | Procedure: ERCP without sphincterotomy<br>* ERCP with sphincter manometry, but no sphincterotomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Success | The primary outcome was a dichotomous (success/failure) variable. Success was defined as patients having a RAPID score of <6 days at months 9 and 12 post-procedure, without re-intervention and without use of prescription analgesics during months 10, 11 and 12 unless used for non-abdominal pain for no more than 14 days. The subject was considered a failure if the 12-month RAPID score was missing or collected outside the acceptable window. If the 9-month RAPID was missing, or outside of the window, then the 6-month value was used when available. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With a Successful Primary Outcome, Out of Those With Abnormal Sphincter Manometry. | Successful outcome was defined using the primary outcome definition of success at 12 months post randomization. Abnormal sphincter manometry was determined as a basal pressure of more than 40mm Hg in both leads. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sphincter of Oddi Dysfunction, Pancreatitis, Sphincterotomy