Clinical trial NCT00688662: Evaluating Predictors & Interventions in Sphincter of Oddi Dysfunction
Official title: A Phase III Randomized Multicenter Clinical Trial of Sphincterotomy for the Treatment of SOD III Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sphincter of Oddi Dysfunction
Keywords: Sphincter of Oddi Dysfunction
Pancreatitis
Sphincterotomy
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2008-06-03
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients diagnosed with the clinical syndrome of SOD, as defined by the Modified Functional Biliary Disorders Module of the Rome III criteria
2. Pain burden of Grade 3 or higher on RAPID Questionnaire.
3. Cholecystectomy more than 90 days before enrollment.
4. 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.
5. Normal abdominal imaging by CT or MR/MRCP with bile duct reported at ≤9mm.
6. Upper endoscopy examination without findings to explain the pain.
7. Pain persisting despite a one trial of acid suppressant medications for one month (if tolerated).
8. Pain persisting despite a trial of antispasmodics.
9. 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:

1. Prior ERCP treatment.
2. Age \< 18 or Age \> 65.
3. 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).
4. Prior gastric resection or surgery involving biliary diversion.
5. 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.
6. Daily use of prescription analgesics over the previous month.
7. Abdominal discomfort every day for the past month at level of 3 or more on a scale of 1-10.
8. Presence of significant psychiatric disorders:

   1. Lifetime psychotic disorders, bipolar disorder;
   2. Substance use disorders within 6 months;
   3. Eating disorders within 2 years
   4. Moderate \& severe depression defined by BDI-II (Beck Depression Inventory) cutoff scores \>22 (unless receiving stable psychiatric therapy for six weeks); and/or,
   5. 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.
9. 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.
10. Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation.

ERCP Criteria:

1. Pancreas divisum (complete or partial) (known or discovered at study ERCP).
2. Any pathology found at ERCP (except sphincter hypertension).
3. Failed pancreatic manometry.

Primary outcomes:
measure: Percentage of Participants With Success
timeFrame: 1 year
Secondary outcomes:
measure: Percentage of Patients With a Successful Primary Outcome, Out of Those With Abnormal Sphincter Manometry.
timeFrame: 1 year
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Midwest Therapeutic Endoscopy Consultants
state: Missouri
city: Charleston
country: United States
facility: Medical University of South Carolina Digestive Disease Center
state: South Carolina
city: Dallas
country: United States
facility: Methodist Dallas Medical Center
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Medical Universtiy of South Carolina
name: Joseph Romagnuolo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Martin Freeman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Mason Medical Center
name: Richard Kozarek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Evan Fogel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MUSC Digestive Disease Center
name: Peter Cotton, MD
role: STUDY_CHAIR
affiliation: Digestive Health Associates of Texas
name: Paul Tarnasky, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Therapeutic Endoscopy Consultants
name: Giuseppe Aliperti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Priya Jamidar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Jose Serrano
role: STUDY_DIRECTOR
References:
citation: Yaghoobi M, Pauls Q, Durkalski V, Romagnuolo J, Fogel EL, Tarnasky PR, Aliperti G, Freeman ML, Kozarek RA, Jamidar PA, Wilcox CM, Elta GH, Hawes RH, Wood-Williams A, Cotton PB. Incidence and predictors of post-ERCP pancreatitis in patients with suspected sphincter of Oddi dysfunction undergoing biliary or dual sphincterotomy: results from the EPISOD prospective multicenter randomized sham-controlled study. Endoscopy. 2015 Oct;47(10):884-90. doi: 10.1055/s-0034-1392418. Epub 2015 Jul 10.
citation: Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, Aliperti G, Freeman M, Kozarek R, Jamidar P, Wilcox M, Serrano J, Brawman-Mintzer O, Elta G, Mauldin P, Thornhill A, Hawes R, Wood-Williams A, Orrell K, Drossman D, Robuck P. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220.
citation: Romagnuolo J, Cotton PB, Durkalski V, Pauls Q, Brawman-Mintzer O, Drossman DA, Mauldin P, Orrell K, Williams AW, Fogel EL, Tarnasky PR, Aliperti G, Freeman ML, Kozarek RA, Jamidar PA, Wilcox CM, Serrano J, Elta GH. Can patient and pain characteristics predict manometric sphincter of Oddi dysfunction in patients with clinically suspected sphincter of Oddi dysfunction? Gastrointest Endosc. 2014 May;79(5):765-72. doi: 10.1016/j.gie.2013.11.037. Epub 2014 Jan 25.
citation: Cotton PB, Durkalski V, Orrell KB, Brawman-Mintzer O, Drossman DA, Wilcox CM, Mauldin PD, Elta GH, Tarnasky PR, Fogel EL, Jagganath SB, Kozarek RA, Freeman ML, Romagnuolo J, Robuck PR. Challenges in planning and initiating a randomized clinical study of sphincter of Oddi dysfunction. Gastrointest Endosc. 2010 Nov;72(5):986-91. doi: 10.1016/j.gie.2010.08.022.