A Study of Serial Magnetic Resonance Cholangiopancreatography (MRCP) Following Morphine-neostigmine and Secretin Provocation in Healthy Volunteers
Condition: Sphincter of Oddi Dysfunction
MeSH terms: Sphincter of Oddi Dysfunction
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Morphine; Neostigmine; 0.9% saline; Secretin; 0.9% saline
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 10mg IM; 1mg IM; 0.1 ml/kg; 1 unit/kg IV; 1ml IM
Intervention MeSH terms: Morphine; Secretin; Neostigmine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Bile ducts; Sphincter of Oddi; Pancreatic ducts