Evaluating Predictors & Interventions in Sphincter of Oddi Dysfunction

NCT ID: NCT00688662

Last Updated: 2018-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 214 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2016-12-31

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.

Conditions

Sphincter of Oddi Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1.ERCP with sphincterotomy

ERCP with sphincterotomy: cutting the biliary sphincter muscle (sphincterotomy)

Group Type: ACTIVE_COMPARATOR

ERCP with sphincterotomy

Intervention Type: PROCEDURE

cutting the biliary sphincter muscle (sphincterotomy)

2.ERCP without sphincterotomy

ERCP without cutting the biliary sphincter muscle (sphincterotomy)

Group Type: PLACEBO_COMPARATOR

ERCP without sphincterotomy

Intervention Type: PROCEDURE

ERCP with sphincter manometry, but no sphincterotomy

Interventions

ERCP with sphincterotomy

cutting the biliary sphincter muscle (sphincterotomy)

Intervention Type: PROCEDURE

ERCP without sphincterotomy

ERCP with sphincter manometry, but no sphincterotomy

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Peter Cotton

Study Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Romagnuolo, MD

Role: PRINCIPAL_INVESTIGATOR

Medical Universtiy of South Carolina

Martin Freeman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Richard Kozarek, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Mason Medical Center

Evan Fogel, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Peter Cotton, MD

Role: STUDY_CHAIR

MUSC Digestive Disease Center

Paul Tarnasky, MD

Role: PRINCIPAL_INVESTIGATOR

Digestive Health Associates of Texas

Giuseppe Aliperti, MD

Role: PRINCIPAL_INVESTIGATOR

Midwest Therapeutic Endoscopy Consultants

Priya Jamidar, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Jose Serrano

Role: STUDY_DIRECTOR

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Locations

Yale University

New Haven, Connecticut, United States

Indiana University

Indianapolis, Indiana, United States

University of Minnesota

Minneapolis, Minnesota, United States

Midwest Therapeutic Endoscopy Consultants

St Louis, Missouri, United States

Medical University of South Carolina Digestive Disease Center

Charleston, South Carolina, United States

Methodist Dallas Medical Center

Dallas, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26165739 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24867013 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24472759 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21034899 (View on PubMed)

Other Identifiers

U01DK074739

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DK074739

Identifier Type: -

Identifier Source: org_study_id