MAP-1 v2.0
Research type
Research Study
Full title
International prospective evaluation of novel biomarkers to detect and predict the severity of drug-associated acute pancreatitis in adults (Markers in Acute Pancreatitis-1, MAP-1)
IRAS ID
283991
Contact name
Robert Sutton
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Acute pancreatitis is a common inflammatory disorder of the pancreas that can lead to organ failure and death. While gallstones and alcohol excess cause most cases, adverse reactions to drugs are an important cause. Drug-associated acute pancreatitis accounts for up to 5% of all cases and is the principal clinical presentation of drug-induced pancreatic injury, whether in early or late phase clinical trials or during licenced use of drug treatments for other diseases. Although acute pancreatitis can be diagnosed using routine serum amylase and/or lipase, there are no accurate means to predict disease course on admission to hospital. Similarly, serum amylase and/or lipase lack sensitivity to detect and specificity to exclude sub-clinical drug-induced pancreatic injury. As a result, drug development is impeded by the lack of accurate early biomarkers, since any pre-clinical pancreatic toxicity will deter investigators from human trials, the lack of sensitivity to detect acute pancreatitis may give false reassurance, while the lack of specificity may lead to inappropriate abandonment of drugs in development. Alternative pancreatic enzymes and/or enzyme activation peptides could be used as both diagnostic and prognostic biomarkers. In addition, microRNAs have particular promise as biomarkers for these purposes, as these are important in disease mechanisms, have significant potential as diagnostic and prognostic biomarkers, and are therapeutic targets. MAP-1 will test the clinical utility of selected circulating and urinary microRNAs measured by qRT-PCR and a selected circulating and/or urinary pancreatic enzyme marker measured by immunoprecipitation and liquid chromatography/tandem mass spectrometry in acute pancreatitis and specifically as potentially accurate safety signals for drug-associated acute pancreatitis in adults. Comparative data will be obtained for C-reactive protein and interleukin-6 at the same time points, optional biomarkers currently used to determine interventional management during acute pancreatitis.
Lay summary of study results:
This study assesses blood tests to identify and predict the severity of acute pancreatitis, with a focus on acute pancreatitis caused by drugs for other diseases. It is hoped that the tests can be used in the development of new drugs to find out if new drugs damage the pancreas. The three types of blood tests are firstly standard tests already used for acute pancreatitis, secondly new microRNA tests of molecules controlling how cells make new parts, and thirdly protein tests made by the pancreas (enzymes). The standard tests cannot predict the severity of acute pancreatitis. Ideally there would be tests that can do both: identify and predict the severity of acute pancreatitis. There were other groups in the study to find out if the blood tests were specific for acute pancreatitis. The groups in the study included patients with (1) acute pancreatitis caused by drugs [39 patients recruited], (2) acute pancreatitis from other causes [41 patients], (3) chronic pancreatitis [23 patients], (4) pancreas cancer [10 patients], and (5) diabetes mellitus [25 patients] as well as (6) healthy volunteers [56 people].
Although the number of participants was fewer than expected, an adequate number of participants were recruited to assess the blood tests. The new microRNA and protein tests were found to identify acute pancreatitis accurately. The role of these tests in clinical practice requires further work to find out if the tests can be used to diagnose acute pancreatitis from among the very many diseases that cause similar symptoms. Finding out whether the new tests can predict severity is still being worked on. If the new tests can predict severity accurately, this will add to the need for further work to find out their role in clinical practice.REC name
London - Queen Square Research Ethics Committee
REC reference
21/LO/0635
Date of REC Opinion
5 Jan 2022
REC opinion
Further Information Favourable Opinion