Secretin for Acute Pancreatitis
| Status: | Not yet recruiting |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 9/29/2018 |
| Start Date: | October 1, 2018 |
| End Date: | November 1, 2019 |
| Contact: | Timothy B Gardner, MD |
| Email: | timothy.b.gardner@hitchcock.org |
| Phone: | 603-650-6472 |
A Phase II Study to Establish the Efficacy of Synthetic Human SecretiN in Human Acute Pancreatitis (SNAP) Study
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.
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.
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
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