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A Study of Serial Magnetic Resonance Cholangiopancreatography (MRCP) Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT01134848
Recruitment Status : Completed
First Posted : June 2, 2010
Last Update Posted : June 2, 2010
Sponsor:
Information provided by:
University of Nottingham

Tracking Information
First Submitted Date  ICMJE May 28, 2010
First Posted Date  ICMJE June 2, 2010
Last Update Posted Date June 2, 2010
Study Start Date  ICMJE January 2009
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2010)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2010)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Serial Magnetic Resonance Cholangiopancreatography (MRCP) Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
Official Title  ICMJE A Randomised, Double Blind Cross-over Study of Serial MRCP Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Diagnostic
Condition  ICMJE Sphincter of Oddi Dysfunction
Intervention  ICMJE
  • Drug: Morphine
    10mg IM
  • Drug: Neostigmine
    1mg IM
  • Drug: 0.9% saline
    0.1 ml/kg
  • Drug: Secretin
    1 unit/kg IV
  • Drug: 0.9% saline
    1ml IM
Study Arms  ICMJE
  • Active Comparator: Morphine-neostigmine
    Interventions:
    • Drug: Morphine
    • Drug: Neostigmine
    • Drug: 0.9% saline
  • Active Comparator: Secretin
    Interventions:
    • Drug: Secretin
    • Drug: 0.9% saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 1, 2010)
10
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2010
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01134848
Other Study ID Numbers  ICMJE C/10/2007
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Paul Cartledge, University of Nottingham
Study Sponsor  ICMJE University of Nottingham
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dileep Lobo, MBBS DM FRCS University of Nottingham
Study Director: Abeed Chowdhury, MB ChB BSc MRCS University of Nottingham
PRS Account University of Nottingham
Verification Date May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP