Sphincter of Oddi DysfunctionEPISODNCT00688662
Evaluating Predictors & Interventions in Sphincter of Oddi Dysfunction
A study testing ERCP with sphincterotomy and ERCP without sphincterotomy in people with Sphincter of Oddi Dysfunction, run by Medical University of South Carolina at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sphincter of Oddi Dysfunction
- What is being tested?
- ERCP with sphincterotomy and ERCP without sphincterotomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 7 sitesUnited States
- Study dates
- Jul 2008to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Medical University of South Carolina Digestive Disease Center
Charleston, South Carolina, 29425
Methodist Dallas Medical Center
Dallas, Texas, 75203
Indiana University
Indianapolis, Indiana, 46202
University of Minnesota
Minneapolis, Minnesota, 55415
Yale University
New Haven, Connecticut, 06510
Virginia Mason Medical Center
Seattle, Washington, 98101
Midwest Therapeutic Endoscopy Consultants
St Louis, Missouri, 63141
About this study
Official title: A Phase III Randomized Multicenter Clinical Trial of Sphincterotomy for the Treatment of SOD III Patients
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.
Read the 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
- Being tested
- ERCP with sphincterotomy, ERCP without sphincterotomy
- Keywords
- Sphincter of Oddi Dysfunction, Pancreatitis, Sphincterotomy
- Medical subject headings
- Sphincter of Oddi Dysfunction, Pancreatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERCP with sphincterotomyProcedure or surgery
cutting the biliary sphincter muscle (sphincterotomy)
ERCP without sphincterotomyProcedure or surgery
ERCP with sphincter manometry, but no sphincterotomy
| Study group | Role | What they receive |
|---|---|---|
| 1.ERCP with sphincterotomy | Active comparator | ERCP with sphincterotomy: cutting the biliary sphincter muscle (sphincterotomy) Receives: Procedure: ERCP with sphincterotomy |
| 2.ERCP without sphincterotomy | Placebo comparator | ERCP without cutting the biliary sphincter muscle (sphincterotomy) Receives: Procedure: ERCP without sphincterotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (1)
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2008 (estimated)
- Study startJul 2008
- Primary completionDec 2013
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sphincter of Oddi DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Cotton, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Investigators
- Joseph Romagnuolo, MD, Principal investigator, Medical Universtiy of South CarolinaMartin Freeman, MD, Principal investigator, University of MinnesotaRichard Kozarek, MD, Principal investigator, Virginia Mason Medical CenterEvan Fogel, MD, Principal investigator, Indiana UniversityPeter Cotton, MD, Study chair, MUSC Digestive Disease CenterPaul Tarnasky, MD, Principal investigator, Digestive Health Associates of TexasGiuseppe Aliperti, MD, Principal investigator, Midwest Therapeutic Endoscopy ConsultantsPriya Jamidar, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00688662
- Sponsor's protocol ID
- DK074739
- Other IDs
- U01DK074739
- Acronym
- EPISOD
- Status last verified
- Mar 2018
- First submitted
- 30 May 2008
- Last updated
- 19 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26165739Cotton 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.
PubMed 24867013Romagnuolo 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.
PubMed 24472759Cotton 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.
PubMed 21034899
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Multicenter Clinical Trial of Sphincterotomy for the Treatment of SOD III Patients
- ClinicalTrials.gov ID
- NCT00688662
- Acronym / sponsor ID
- EPISOD / DK074739
- Conditions
- Sphincter of Oddi Dysfunction
- Keywords
- Sphincter of Oddi Dysfunction, Pancreatitis, Sphincterotomy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 214 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2008
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 3 Jun 2008 (estimated)
- Results
- Posted 28 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1.ERCP with sphincterotomy | Active comparator | Procedure: ERCP with sphincterotomyERCP with sphincterotomy: cutting the biliary sphincter muscle (sphincterotomy) |
| 2.ERCP without sphincterotomy | Placebo comparator | Procedure: ERCP without sphincterotomyERCP without cutting the biliary sphincter muscle (sphincterotomy) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERCP with sphincterotomycutting the biliary sphincter muscle (sphincterotomy) | Procedure or surgery | 1.ERCP with sphincterotomy |
| ERCP without sphincterotomyERCP with sphincter manometry, but no sphincterotomy | Procedure or surgery | 2.ERCP without sphincterotomy |
Primary outcome
Percentage of Participants With Success
Time frame: 1 year
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 secondary outcome
Percentage of Patients With a Successful Primary Outcome, Out of Those With Abnormal Sphincter Manometry.
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26165739Yaghoobi 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.
- Derived from this study: PubMed 24867013Cotton 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.
- Derived from this study: PubMed 24472759Romagnuolo 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.
- Derived from this study: PubMed 21034899Cotton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Romagnuolo, MD principal investigator
Medical Universtiy of South Carolina
Martin Freeman, MD principal investigator
University of Minnesota
Richard Kozarek, MD principal investigator
Virginia Mason Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ERCP with sphincterotomy and ERCP without sphincterotomy in people with Sphincter of Oddi Dysfunction, run by Medical University of South Carolina at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Success (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00688662, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2018.