Secretin for Acute Pancreatitis (SNAP)

April 8, 2019 updated by: ChiRhoClin, Inc.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Cohort X
no secretin administered. All observations
ACTIVE_COMPARATOR: Cohort 1
32 mcg (<50kg) or 40 mcg (≥50kg) secretin two times a day (40 mcg; q 12 hrs)
Drug: Secretin
Drug to stimulate pancreatic secretion
Other Names:
  • ChiRhoStim®
ACTIVE_COMPARATOR: Cohort 2
32 mcg (<50kg) or 40 mcg (≥50kg) secretin four times a day (40 mcg; q 6 hrs)
Drug: Secretin
Drug to stimulate pancreatic secretion
Other Names:
  • ChiRhoStim®
ACTIVE_COMPARATOR: Cohort 3
32 mcg (<50kg) or 40 mcg (≥50kg) secretin six times a day (40 mcg; q 4 hrs)
Drug: Secretin
Drug to stimulate pancreatic secretion
Other Names:
  • ChiRhoStim®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CRP level
Time Frame: 96 hours and through study completion an average of day 7
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pro- and anti-inflammatory markers
Time Frame: Day 1, Day 2, Day 3, 96 hours and through study completion an average of day 7
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
Day 1, Day 2, Day 3, 96 hours and through study completion an average of day 7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Hemoconcentration measurement
Time Frame: 96 hours and through study completion an average of day 7
Change in hematocrit from admission
96 hours and through study completion an average of day 7
Change in Hemoconcentration measurements
Time Frame: 96 hours and through study completion an average of day 7
Change in blood urea nitrogen from admission
96 hours and through study completion an average of day 7
Acute Pancreatitis Activity Score
Time Frame: 96 hours and through study completion an average of day 7
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
Overall hospital stay
Time Frame: 96 hours and through study completion an average of day 7
Length of hospitalization
96 hours and through study completion an average of day 7
Rate of Adverse Events
Time Frame: 30 days following the last administration of study treatment
Will be reported as a rate per cohort.
30 days following the last administration of study treatment
Readmission Rate
Time Frame: 30 days following the last administration of study treatment
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ChiRhoClin, Inc.

Collaborators

Dartmouth-Hitchcock Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 1, 2018

Primary Completion (ANTICIPATED)

October 1, 2019

Study Completion (ANTICIPATED)

November 1, 2019

Study Registration Dates

First Submitted

August 24, 2018

First Submitted That Met QC Criteria

September 26, 2018

First Posted (ACTUAL)

September 27, 2018

Study Record Updates

Last Update Posted (ACTUAL)

April 10, 2019

Last Update Submitted That Met QC Criteria

April 8, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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