Sphincter of Oddi DysfunctionPhase 4NCT01134848
A Study of Serial Magnetic Resonance Cholangiopancreatography (MRCP) Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
A Phase 4 study testing Morphine, Neostigmine and 0.9% saline in people with Sphincter of Oddi Dysfunction, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
The sphincter of Oddi is a circular band of muscle which controls the flow of pancreatic juices and bile into the small intestine. Abnormal function of the Sphincter of Oddi, known as Sphincter of Oddi dysfunction (SOD), can lead to recurrent episodes of abdominal pain. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Sphincter of Oddi Dysfunction
- What is being tested?
- Morphine, Neostigmine and 0.9% saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2009to Feb 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy age matched and sex matched volunteers
- No history of chronic abdominal pain
- No previous abdominal surgery
- No history suggestive of gastrointestinal motility disorders
- No history of regular medication or substance abuse
Who cannot join
- Acute illness within preceding 6 weeks
- Participation in another study within 3 months
- Allergy to morphine or neostigmine
- Pregnancy
- Refusal to consent to the study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Nottingham
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: A Randomised, Double Blind Cross-over Study of Serial MRCP Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
The sphincter of Oddi is a circular band of muscle which controls the flow of pancreatic juices and bile into the small intestine. Abnormal function of the Sphincter of Oddi, known as Sphincter of Oddi dysfunction (SOD), can lead to recurrent episodes of abdominal pain. Making a diagnosis of SOD is difficult and is currently achieved using an invasive pressure test. This pressure test is associated with some adverse effects including inflammation of the pancreas gland. We are investigating an alternative test in which medication is given to provoke spasm of the sphincter. Following provocation, blood can be sampled to detect changes in blood composition and changes in sphincter anatomy can be evaluated using specialized imaging techniques.
Our aim is to study and compare the effects of two provocation medications (morphine-prostigmine and secretin) on biliary and pancreatic ductal anatomy, using dynamic serial MRCP in healthy volunteers.
Our hypothesis is that morphine-neostigmine provocation results in greater changes in biliary and pancreatic ductal anatomy when assessed using dynamic serial MRCP.
Read the detailed description
The sphincter of Oddi (SO), which encases the distal common bile duct (CBD) and pancreatic duct (PD), comprises a fibromuscular complex to control the flow of biliary and pancreatic secretions into the duodenum. Aberrant function of the SO, known as Sphincter of Oddi dysfunction (SOD), can lead to recurrent episodes of biliary or pancreatic type pain. Both surgical sphincteroplasty and endoscopic sphincterotomy can improve symptoms in some patients who are suspected to have SOD. However, poor results are obtained in a significant proportion reflecting the difficulties in achieving an accurate diagnosis and also in selecting those patients likely to benefit from these procedures. A number of investigative modalities have been employed in the assessment of SOD. Of the available diagnostic tests sphincter of Oddi manometry (SOM) is considered the gold standard, but is associated with a high rate of post procedure morbidity including pancreatitis and biliary sepsis.
It is therefore unsurprising that attention has focussed on non-invasive diagnostic tests. Developments in magnetic resonance cholangiopancreatography (MRCP) have allowed for the detailed non-invasive assessment of biliary and pancreatic ductal morphology and can be used in conjunction with intravenous secretin provocation (ss-MRCP). Evaluations of this technique have so far been disappointing, demonstrating only a modest concordance with SOM in patients suspected with SOD.
The morphine-prostigmine provocation test (Nardi test) has previously been utilised as a screening test in patients with symptoms suggestive of SOD. It is performed by giving an intramuscular injection of morphine 10mg and prostigmine 1mg, with a positive test indicated by the reproduction of pain or a fourfold increase in either serum amylase or lipase levels. As enzymatic changes have been shown to occur in healthy subjects and in those with irritable bowel syndrome, the test has largely fallen out of favour. However, a recent publication has suggested morphine used as a pharmacological provocation agent can improve ductal distension and aid the differentiation of pancreaticobiliary variants on MRCP. To date this has not been investigated in a randomised or blinded study and we have therefore proposed to examine the effects of morphine-neostigmine and secretin provocation on gallbladder volume and biliary and pancreatic ductal morphology in healthy volunteers using serial MRCP.
- Conditions
- Sphincter of Oddi Dysfunction
- Being tested
- Morphine, Neostigmine, 0.9% saline, Secretin
- Keywords
- Bile ducts, Sphincter of Oddi, Pancreatic ducts
- Medical subject headings
- Sphincter of Oddi Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
10mg IM
NeostigmineDrug
1mg IM
0.9% salineDrug
0.1 ml/kg
SecretinDrug
1 unit/kg IV
0.9% salineDrug
1ml IM
| Study group | Role | What they receive |
|---|---|---|
| Morphine-neostigmine | Active comparator | Not described Receives: Drug: Morphine; Drug: Neostigmine; Drug: 0.9% saline |
| Secretin | Active comparator | Not described Receives: Drug: Secretin; Drug: 0.9% saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum amylase (U/L)
Measured: 0, 60, 120, 180 and 240 minutes
Serum lipase (U/L)
Measured: 0, 60, 120, 180 and 240 minutes
Liver function tests
Measured: 0, 60, 120, 180 and 240 minutes
Secondary outcomes (4)
Pancreatic duct diameter (mm)
Measured: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Pancreatic duct length (mm)
Measured: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Common bile duct diameter (mm)
Measured: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Gallbladder volume (mm3)
Measured: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2010 (estimated)
- Study startJan 2009
- Primary completionFeb 2010
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sphincter of Oddi DysfunctionStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Investigators
- Dileep Lobo, MBBS DM FRCS, Principal investigator, University of NottinghamAbeed Chowdhury, MB ChB BSc MRCS, Study director, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01134848
- Sponsor's protocol ID
- C/10/2007
- Status last verified
- May 2010
- First submitted
- 28 May 2010
- Last updated
- 2 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double Blind Cross-over Study of Serial MRCP Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01134848
- Acronym / sponsor ID
- C/10/2007
- Conditions
- Sphincter of Oddi Dysfunction
- Keywords
- Bile ducts, Sphincter of Oddi, Pancreatic ducts
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 2 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The sphincter of Oddi is a circular band of muscle which controls the flow of pancreatic juices and bile into the small intestine. Abnormal function of the Sphincter of Oddi, known as Sphincter of Oddi dysfunction (SOD), can lead to recurrent episodes of abdominal pain. Making a diagnosis of SOD is difficult and is currently achieved using an invasive pressure test. This pressure test is associated with some adverse effects including inflammation of the pancreas gland. We are investigating an alternative test in which medication is given to provoke spasm of the sphincter. Following provocation, blood can be sampled to detect changes in blood composition and changes in sphincter anatomy can be evaluated using specialized imaging techniques.
Our aim is to study and compare the effects of two provocation medications (morphine-prostigmine and secretin) on biliary and pancreatic ductal anatomy, using dynamic serial MRCP in healthy volunteers.
Our hypothesis is that morphine-neostigmine provocation results in greater changes in biliary and pancreatic ductal anatomy when assessed using dynamic serial MRCP.
Detailed description
The sphincter of Oddi (SO), which encases the distal common bile duct (CBD) and pancreatic duct (PD), comprises a fibromuscular complex to control the flow of biliary and pancreatic secretions into the duodenum. Aberrant function of the SO, known as Sphincter of Oddi dysfunction (SOD), can lead to recurrent episodes of biliary or pancreatic type pain. Both surgical sphincteroplasty and endoscopic sphincterotomy can improve symptoms in some patients who are suspected to have SOD. However, poor results are obtained in a significant proportion reflecting the difficulties in achieving an accurate diagnosis and also in selecting those patients likely to benefit from these procedures. A number of investigative modalities have been employed in the assessment of SOD. Of the available diagnostic tests sphincter of Oddi manometry (SOM) is considered the gold standard, but is associated with a high rate of post procedure morbidity including pancreatitis and biliary sepsis.
It is therefore unsurprising that attention has focussed on non-invasive diagnostic tests. Developments in magnetic resonance cholangiopancreatography (MRCP) have allowed for the detailed non-invasive assessment of biliary and pancreatic ductal morphology and can be used in conjunction with intravenous secretin provocation (ss-MRCP). Evaluations of this technique have so far been disappointing, demonstrating only a modest concordance with SOM in patients suspected with SOD.
The morphine-prostigmine provocation test (Nardi test) has previously been utilised as a screening test in patients with symptoms suggestive of SOD. It is performed by giving an intramuscular injection of morphine 10mg and prostigmine 1mg, with a positive test indicated by the reproduction of pain or a fourfold increase in either serum amylase or lipase levels. As enzymatic changes have been shown to occur in healthy subjects and in those with irritable bowel syndrome, the test has largely fallen out of favour. However, a recent publication has suggested morphine used as a pharmacological provocation agent can improve ductal distension and aid the differentiation of pancreaticobiliary variants on MRCP. To date this has not been investigated in a randomised or blinded study and we have therefore proposed to examine the effects of morphine-neostigmine and secretin provocation on gallbladder volume and biliary and pancreatic ductal morphology in healthy volunteers using serial MRCP.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine-neostigmine | Active comparator | Drug: Morphine, Drug: Neostigmine, Drug: 0.9% saline |
| Secretin | Active comparator | Drug: Secretin, Drug: 0.9% saline |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Healthy age matched and sex matched volunteers
- No history of chronic abdominal pain
- No previous abdominal surgery
- No history suggestive of gastrointestinal motility disorders
- No history of regular medication or substance abuse
Key exclusion criteria (5 listed)
- Acute illness within preceding 6 weeks
- Participation in another study within 3 months
- Allergy to morphine or neostigmine
- Pregnancy
- Refusal to consent to the study
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 |
|---|---|---|
| Morphine10mg IM | Drug | Morphine-neostigmine |
| Neostigmine1mg IM | Drug | Morphine-neostigmine |
| 0.9% saline0.1 ml/kg | Drug | Morphine-neostigmine |
| Secretin1 unit/kg IV | Drug | Secretin |
| 0.9% saline1ml IM | Drug | Secretin |
Primary outcome
Serum amylase (U/L)
Time frame: 0, 60, 120, 180 and 240 minutes
Serum lipase (U/L)
Time frame: 0, 60, 120, 180 and 240 minutes
Liver function tests
Time frame: 0, 60, 120, 180 and 240 minutes
4 secondary outcomes
Pancreatic duct diameter (mm)
Time frame: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Pancreatic duct length (mm)
Time frame: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Common bile duct diameter (mm)
Time frame: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Gallbladder volume (mm3)
Time frame: 0, 5, 30, 60, 90, 120, 150 and 180 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2010.
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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.
Dileep Lobo, MBBS DM FRCS principal investigator
University of Nottingham
Abeed Chowdhury, MB ChB BSc MRCS study director
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Morphine, Neostigmine and 0.9% saline in people with Sphincter of Oddi Dysfunction, run by University of Nottingham at 1 site in United Kingdom.
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 5 inclusion and 5 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 2 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Serum amylase (U/L) (time frame: 0, 60, 120, 180 and 240 minutes). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jun 2010.