Secretin for Acute Pancreatitis

Pancreatitis, Acute Clinical Trial

— SNAP  

Official title:

A Phase II Study to Establish the Efficacy of Synthetic Human SecretiN in Human Acute Pancreatitis (SNAP) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03686618
• Other study ID #: 2017-01
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2018
• Est. completion date: November 1, 2019

Study information

• Verified date: April 2019
• Source: ChiRhoClin, Inc.
• Contact: Timothy B Gardner, MD
• Phone: 603-650-6472
• Email: timothy.b.gardner[@]hitchcock.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatitis
• Pancreatitis, Acute

Intervention

Drug:
• Secretin
Drug to stimulate pancreatic secretion

Locations

Country	Name	City	State
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
ChiRhoClin, Inc.	Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (40)

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Hemoconcentration measurement	Change in hematocrit from admission	96 hours and through study completion an average of day 7
Other	Change in Hemoconcentration measurements	Change in blood urea nitrogen from admission	96 hours and through study completion an average of day 7
Other	Acute Pancreatitis Activity Score	A cumulative measurement of the following parameters: (as referenced from the CRF) higher values represent worse outcome Organ Failure (number of systems) x 100 (each system) SIRS (number of criteria) x 25 (each criteria) Abdominal Pain (1-10) x 5 Morphine Equivalent Dose (mg) X 5 Tolerating Solid Diet (yes = 0, no = 1) X 40	96 hours and through study completion an average of day 7
Other	Overall hospital stay	Length of hospitalization	96 hours and through study completion an average of day 7
Other	Rate of Adverse Events	Will be reported as a rate per cohort.	30 days following the last administration of study treatment
Other	Readmission Rate	Rate will be recorded as number of subjects readmitted within 30 days of final study treatment	30 days following the last administration of study treatment
Primary	Change in CRP level	Change 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	96 hours and through study completion an average of day 7
Secondary	Pro- and anti-inflammatory markers	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-a2, IFN-?, IL-1a, IL-1ß, 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-1a, MIP-1ß, PDGF-AA, PDGF-AB/BB, RANTES, TGF-a, TNF-a, TNF-ß, VEGF, HSP 27, HSP 60, HSP 70, HSP 90 at time of study enrollment, days of secretin administration, 96 hours and at discharge	Day 1, Day 2, Day 3, 96 hours and through study completion an average of day 7