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Resolution of Organ Injury in Acute Pancreatitis - RESORP (RESORP)

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ClinicalTrials.gov Identifier: NCT03342716
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Acute pancreatitis (AP) is inflammation of the pancreas usually triggered by gallstones or drinking excessive alcohol. 80% of people who have an episode of AP will recover without complications. However, 20% will require treatment in high dependency or intensive care for multiple organ dysfunction (AP-MODS). It is known that this negatively affects recovery and can have a lasting effect on health although it is incompletely understood what causes this.

Aim: To recruit 500 patients with acute pancreatitis. Participants will be assessed at recruitment and and again at 3 and 27 months. Recovery of organ function will be serially measured and the presence of novel factors important in recovery assessed.


Condition or disease
Pancreatitis, Acute

Detailed Description:

Acute pancreatitis (AP) is a common and devastating disease with an annual incidence of 22-30 per 100,000 in the UK. The incidence is increasing. AP is most commonly triggered by gallstones or alcohol excess and has a range of outcomes, from complete resolution to death, with an overall mortality in Scotland of 5.2%. AP is characterised by acute inflammation of the pancreas, which initiates a cascade of inflammatory events throughout the body that can lead to multiple organ dysfunction syndrome (MODS) in approximately 25% of AP patients. Mortality in AP is greatest in those patients who develop MODS, with death rates reported to be up to 28%.

The development of persistent organ failure characterises severe AP (SAP) as defined in the revised Atlanta classification, and is strongly predictive of a fatal outcome. A significant proportion of research has focussed on reducing mortality and morbidity in the first week. As a consequence, it remains to be seen whether the patterns of early organ dysfunction are reflected in the causes of long-term mortality and morbidity.

Recently published data from a retrospective analysis of patients admitted to the Royal Infirmary of Edinburgh with acute pancreatitis has shown that the early development of MODS is associated with an increased mortality rate up to 10 years after the index presentation. This strongly suggests that MODS in acute pancreatitis (AP-MODS) has a persistent and deleterious impact on patients' physiological status, though the exact nature of this pathology remains to be characterised. Recent data has indicated that the severity of the first attack of AP significantly influences the risk of progression to chronic pancreatitis, and therefore subsequent long-term morbidity.

This observational clinical cohort study aims to characterise the nature and extent of the pathophysiological impact of SAP on organ function over the first 2 years following the index event and the long-term deleterious effect of SAP. This will be achieved by prospectively evaluating the pathophysiological consequences of an episode of AP by measuring organ system function in patients recruited during a hospital admission with AP. We will obtain an in-depth assessment of patients' health at presentation, and at 3 months and 27 months after the first episode of AP using markers of organ function and/or disease in the peripheral blood. In a nested cohort within the main study cohort, we will conduct cardiorespiratory evaluation tests (including exercise testing), specialised blood tests of the immune system, tests for precision medicine, and imaging to assess structure and function of key organ systems.

The results of this study will inform the design of future interventions designed to improve the long-term prognosis of patients.


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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Resolution of Organ Injury in Acute Pancreatitis - RESORP
Actual Study Start Date : November 27, 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatitis

Group/Cohort
Main cohort
Patients with a clinical or radiological diagnosis of acute pancreatitis (AP)
Nested cohort
Subgroup of patients with a clinical or radiological diagnosis of acute pancreatitis (AP) who will undergo additional assessments and scans



Primary Outcome Measures :
  1. Annual incidence of new-onset type 3c diabetes mellitis in patients with AP [ Time Frame: 57 months ]
    Do patients that have had AP develop type 3c diabetes mellitis more frequently?

  2. Nested cohort only - difference in the 3 month to 27 month change in pancreatic fibrosis index between participants with AP with MODS and those with AP without MODS [ Time Frame: 57 months ]
    Assess any damage to pancreas at 3 and 27 months and monitor how this changes throughout the course of the trial comparing participants with AP only and those with AP and MODS


Secondary Outcome Measures :
  1. Specific gene and promoter sequence variation between participants with AP and AP-MODS [ Time Frame: 63 months ]
    Define any gene and promoter sequence variation between participants with AP and AP-MODS; machine learning approach

  2. miRNA signatures of disease severity and resolution [ Time Frame: 63 months ]
    Comparing patterns of gene expression in mild/moderate/severe cases of AP; machine learning approach

  3. Metabolomic profiling of AP resolution. [ Time Frame: 63 months ]
    Comparing patterns of metabolite expression in mild/moderate/severe cases of AP; machine learning approach

  4. Incidence of premature cellular senescence as a pathological consequence of AP-MODS. [ Time Frame: 63 months ]
    Investigating pathological consequences of AP-MODS compared to AP without MODS

  5. Alteration in immune cell subset phenotype as a long-term response to AP-MODS [ Time Frame: 63 months ]
    Investigating changes to the phenotype of immune cell subsets following an episode of AP; descriptive statistics

  6. Cardiorespiratory dysfunction as a legacy of endothelial injury during AP-MODS [ Time Frame: 63 months ]
    Determination of cardiorespiratory function following AP using physiological measures including cardiopulmonary exercise testing to determine anaerobic threshold. Descriptive measures.


Biospecimen Retention:   Samples With DNA
Both DNA and RNA samples taken at baseline, 3 and 27 month visits


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients treated at the Royal Infirmary Edinburgh with a clinical or radiological diagnosis of acute pancreatitis.
Criteria

Inclusion Criteria:

All patients treated at Royal Infirmary Edinburgh with a clinical or radiological diagnosis of acute pancreatitis will be recruited where possible.

For the potential clinical diagnosis of acute pancreatitis an appropriate clinical history based on compatible clinical features, will be required (i.e. abdominal pain, nausea and/or vomiting), supported by the finding of elevated serum amylase greater than 3x the upper limit of the reference range for the laboratory (currently 300 U/L).

For the radiological diagnosis, if applicable, computerised tomography (CT) and/or ultrasound scan (USS) evidence of acute pancreatitis will be accepted.

Exclusion Criteria:

The following exclusion criteria will be adhered to:

i. Patients under the age of 16 years will be excluded from the present study. ii. Prisoners will be excluded from the present study. iii. Patients lacking the capacity to consent will be excluded but can be included if they regain capacity.

Additional exclusions will apply only to those patients being considered for the nested cohort study:

iv. Patients not able to undergo MRI scanning for technical reasons will be excluded (e.g. those with cochlear implants, implanted pacemaker) v. Patients with a known allergy to salbutamol


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03342716


Contacts
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Contact: Julia Boyd 0131 651 9908 julia.boyd@ed.ac.uk
Contact: Chris Coner 0131 242 9446 researchgovernance@ed.ac.uk

Locations
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United Kingdom
Royal Infirmary of Edinburgh Recruiting
Edinburgh, United Kingdom
Contact: Julia Boyd    0131 651 9908    julia.boyd@ed.ac.uk   
Principal Investigator: Damian Mole         
Sponsors and Collaborators
University of Edinburgh
Medical Research Council
Investigators
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Study Director: Damian J Mole, MB ChB The University of Edinburgh

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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03342716     History of Changes
Other Study ID Numbers: v8 01 Dec 2017
MR/P008887/1 ( Other Grant/Funding Number: Medical Research Council )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Edinburgh:
Pancreatitis
Multiple Organ Dysfunction Syndrome
Additional relevant MeSH terms:
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Pancreatitis
Pancreatic Diseases
Digestive System Diseases