Secretin for Acute Pancreatitis
Secretin for Acute Pancreatitis
Acute pancreatitis is a frequently devastating pancreatic inflammatory process that results
 in extensive morbidity, mortality, and hospitalization costs. The incidence of acute
 pancreatitis has been increasing over the last decade with an overall mortality rate of 5%,
 although it may be as high as 30% in the most severe cases. It was the most common inpatient
 gastrointestinal diagnosis in 2009, totaling over 270,000 hospitalizations with estimated
 "inpatient costs" of over 2.5 billion dollars in the United States. However, despite the
 significant impact to both patients and the healthcare system, there is no proven
 pharmacologic therapy that improves important clinical outcomes in acute pancreatitis. The
 release of bicarbonate rich fluid into the pancreatic duct from the ductal cells is an
 important mechanism to protect against pancreatitis by two distinct mechanisms:

 1. "Flushing" activated enzymes out of the pancreas and into the duodenum thereby
 preventing accumulation of activated enzymes within the pancreatic acinus

 2. Directly alkalinizing the acinar cells, which limits intra-acinar cell damage by
 improving trafficking of inappropriately activated intra-acinar enzymes along the apical
 membrane.

 In addition to standard care, patients will be divided into 4 cohorts. Cohorts 1,2 and 3 will
 be treated with different doses of intravenous synthetic human secretin. Cohort X will not
 receive human secretin, but all datapoints and specimens will be collected. The patient
 cohorts will be entered into the study as follows: Cohort X; Cohort 1; Cohort 2; Cohort 3. 5
 patients in each cohort will be evaluated at each center (for a total of n=10 at both centers
 for each cohort). Dosing will start within 24 hours of hospitalization with no further
 synthetic human secretin administration beyond Day 3. Patients will continue to be followed
 for 7 days or until discharge, whichever comes first. Any data recorded to that point would
 be included in an intent-to-treat analysis. The primary objective is to perform a Phase II
 Pilot Study to explore the efficacy of intravenous synthetic human secretin as a
 pharmacologic adjunct to modulate the severity of human acute (non-obstructive) pancreatitis.
This is a prospective, phase II exploratory pilot study using different dose frequencies of
 intravenous human secretin in patients with non-obstructive, interstitial acute pancreatitis.
 All enrolled patients will receive standard of care therapy in regard to fluid resuscitation,
 pain control, CT scan or ultrasound imaging and nutritional support. In addition to standard
 of care, patients will be divided into 4 cohorts of 10 patients. Cohorts 1,2 and 3 will
 receive different doses of intravenous synthetic human secretin. Cohort X will not receive
 drug. Dosing will start within 24 hours of hospitalization with no further secretin
 administration beyond Day 3. Patients will continue to be followed until discharge. The
 primary study endpoint will be the decrease in serum C-reactive protein (CRP) level by 50%
 within 96 hours and/or at discharge compared with CRP level at admission to determine optimal
 frequency of dosing. Secondary study endpoints will include: 1) Serum measurements of pro-
 and anti-inflammatory cytokines including sCD40L, EGF, Eotaxin/CCL11, FGF-2, Flt-3 ligand,
 Fractalkine, G-CSF, GM-CSF, GRO, IFN-α2, IFN-γ, IL-1α, IL-1β, IL-1ra, IL-2, IL-3, IL-4, IL-5,
 IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17A, IP-10, MCP-1,
 MCP-3, MDC (CCL22), MIP-1α, MIP-1β, PDGF-AA, PDGF-AB/BB, RANTES, TGF-α, TNF-α, TNF-β, VEGF,
 HSP 27, HSP 60, HSP 70, HSP 90 at time of study enrollment, days of secretin administration,
 96 hours and at discharge 2) Clinically relevant outcome measures including hemoconcentration
 (fall in blood urea nitrogen and hematocrit from admission), decrease in patient admission
 pain scores (visual analogue scale), decrease in systemic inflammatory response, and
 tolerance of oral nutrition 3) Calculation of the Dynamic Acute Pancreatitis Score - organ
 failure, systemic inflammatory response syndrome, abdominal pain, requirement for opiates and
 ability to tolerate oral intake 4) Length of hospitalization, need for intensive care unit
 transfer, mortality, need for surgical, endoscopic or percutaneous intervention 5)
 Development of pancreatic necrosis and/or persistent organ failure and 6) Adverse events and
 30 day readmission rate.
Inclusion Criteria:

 1. Patient is male or female ≥18 years of age

 2. Patient voluntarily signed written, informed consent agreement.

 3. If patient is female and not more than 1 year post-menopausal, or surgically sterile,
 must use medically accepted form of contraception or abstain from sexual activities
 during study

 4. Patient has acute pancreatitis as defined by the Atlanta Classification of 2012

 5. No evidence of obstructive pancreatitis on available cross-sectional imaging

 Exclusion Criteria:

 1. Pancreatitis with duct obstruction or severe acute pancreatitis defined by Atlanta
 Classification

 2. Pregnant woman, nursing mothers, or women of childbearing potential not on birth
 control

 3. Known adverse reaction to human secretin