Clincosm LogoSign in Get a demo

SNAP: Secretin for Acute Pancreatitis

Sponsor
ChiRhoClin, Inc. (Industry)
Overall Status
Unknown status
CT.gov ID
NCT03686618
Collaborator
Dartmouth-Hitchcock Medical Center (Other)
40
Enrollment
1
Location
4
Arms
13
Anticipated Duration (Months)
3.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
40 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The study is not blinded and does not require any randomization codes. Ten patients each will receive one of three treatments for Days 1, 2, and 3: No secretin - standard of care and observation (Cohort X) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 12 hours (Cohort 1) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 6 hours (Cohort 2) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 4 hours (Cohort 3)The study is not blinded and does not require any randomization codes. Ten patients each will receive one of three treatments for Days 1, 2, and 3:No secretin - standard of care and observation (Cohort X) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 12 hours (Cohort 1) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 6 hours (Cohort 2) 32 mcg (<50kg) or 40 mcg (≥50kg)IV Bolus every 4 hours (Cohort 3)
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study to Establish the Efficacy of Synthetic Human SecretiN in Human Acute Pancreatitis (SNAP) Study
Actual Study Start Date :
Oct 1, 2018
Anticipated Primary Completion Date :
Oct 1, 2019
Anticipated Study Completion Date :
Nov 1, 2019

Arms and Interventions

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®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in CRP level [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

    Secondary Outcome Measures

    1. Pro- and anti-inflammatory markers [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

    Other Outcome Measures

    1. Change in Hemoconcentration measurement [96 hours and through study completion an average of day 7]

      Change in hematocrit from admission

    2. Change in Hemoconcentration measurements [96 hours and through study completion an average of day 7]

      Change in blood urea nitrogen from admission

    3. Acute Pancreatitis Activity Score [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

    4. Overall hospital stay [96 hours and through study completion an average of day 7]

      Length of hospitalization

    5. Rate of Adverse Events [30 days following the last administration of study treatment]

      Will be reported as a rate per cohort.

    6. Readmission Rate [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756

    Sponsors and Collaborators

    • ChiRhoClin, Inc.
    • Dartmouth-Hitchcock Medical Center

    Investigators

    • Principal Investigator: Timothy B Gardner, MD, Dartmouth-Hitchcock Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    ChiRhoClin, Inc.
    ClinicalTrials.gov Identifier:
    NCT03686618
    Other Study ID Numbers:
    • 2017-01
    First Posted:
    Sep 27, 2018
    Last Update Posted:
    Apr 10, 2019
    Last Verified:
    Apr 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Pancreatitis
    Secretin

    Study Results

    No Results Posted as of Apr 10, 2019