Preclincal Models & Clinical Endpoints

Clinical Trial Endpoints

Well-defined endpoints that capture patient-reported outcomes are critical in advancing care in recurrent acute (RAP) and chronic pancreatitis (CP). To do so, Mission: Cure has identified clinically meaningful outcomes from patients and providers to be measured in clinical trials for recurrent acute and chronic pancreatitis patients. We encourage researchers who are planning clinical trials around pancreatitis to incorporate the following endpoints. For more details on our methodology, please consult the table below.

Mandatory DomainPROMs/Measurements
Pain Intensity, other (adults)COMPAT/COMPAT-SF
Pain Intensity and Interference (adults)Brief Pain Inventory (BPI)/BPI SF
Pain Interference (adults)PROMIS Bank v1.1 – Pain Interference
Social Roles/ActivitiesPROMIS Short Form v2.0 – Social roles and activities
Nutrition/EPIClinical measurements (weight, vitamins, etc)
AP Attacks/FlaresNo validated measure

Preclinical Models

Here, researchers and drug developers can find preclinical pancreatitis models. Each category of pre-clinical model has advantages and disadvantages that should be considered when designing pre-clinical studies.

Preclinical Models Report

Preclinical Models Sheet

GEMM Models
Model TypeTargetClassChronic/Acute
mPRSS1 R122H GEMMPRSS1MouseAcute Pancreatitis
hPRSS1 R122H /N291GEMMPRSS1MouseAcute pancreatitis, chronic pancreatitsAthwal et al. 2014
PRSS1 R122HGEMMPRSS1MouseAcute pancreatitis, chronic pancreatitsHuang et al. 2019
PRRS2 and PRSS1 R122HGEMMPRSS2/PRSS1MouseAcute pancreatitis, chronic pancreatitsWang et al. 2022
Ela-creERT;ratPRSSII (hereditary pancreatitis)
GEMMTryspinMouseAcute pancreatitisGaiser et al. 2011
Transgenic PRSS1R122HGEMMPRSS1MouseAcute pancreatitis (Cerulein induced)

Chronic pancreatitis after 70 days of Cerulein tx
Gui et al. 2020
The T7D23A mouse modelGEMMTryspinMouseAcute pancreatitis (age 3-5 weeks)
Chronic Pancreatitis (1 -2 months)
Geiz et al. 2018
T7K24R mouse modelGEMMTryspinMouseAcute pancreatitis (Cerulein induced)

Chronic pancreatitis- Cerulein induced (2 days, sacrificed 3 or 10 days after last injection)
Jancso et al. 2020
SPINK3GEMMSPINKMouseAcute Pancreatitis (Cerulein induced)Ohmuraya et al. 2005
IL-1B overexpressingGEMMIL-1bMouseChronic pancreatitisMarrache F, et al. Gastroenterology 2008;135:1277–1287.
Atg5-knockout /deletionGEMMMouseKlauss et al.

Saloman et al.

Merry and Petrov
Atg7-knockout /deletionGEMMMouseKlauss et al.

Merry and Petrov
IKKa knockout /deletion

GEMMMouseKlauss et al.

Saloman et al.
LAMP2 knockout/defficiencyGEMMMouseKlauss et al.

Saloman et al.

Merry and Petrov
PERK knockoutGEMMMouseKlauss et al.

Saloman et al.

Merry and Petrov
IKK2 Transgenic OverexpressionGEMMMouseKlauss et al.
Mice lacking cilia in pancreatic cellsGEMMMouseKlauss et al.
Kif3a deletionGEMMMouseKlauss et al.

Saloman et al.

Merry and Petrov
WBN/KobGEMMMouseKlauss et al.

Saloman et al.
Cpa1 pN256KGEMMMouseMerry and Petrov
Tgf-B1 OverexpressionGEMMTGFbMouseMerry and Petrov

Sanvito et al.
CFTR–GEMMCFTRMouseDurie et al.
PNLIPP p.T122MGEMMPancreatic triglyceride lipase (PNLIP)MouseChronic pancreatitisZhu et al. 2023
Ctrb 1-delGEMMCTRB1MouseAcute pancreatitis, chronic pancreatitisGeisz, Jansco et al. 2019
Secretagogue Models
Model TypeTargetClassChronic/AcuteReferences
Cerulein: APSecretagogueMouse, rat, hamster, dogAcute pancreatitisKlauss et al.

Saloman et al.

Lampel et al. 1977
Cerulein: RAP/CPSecretagogueMouse, rat, hamster, dogChronic pancreatitisKlauss et al.

Saloman et al.
secretin, cholecystokinin-octapeptide, bombesin, and carbacholSecretagogueGuinea pig, hamster, rabbitPadfield et al. 1989
Ali et al. 1990
Amino Acid Models
Model TypeTargetClassAcute/ChronicReferences
L-arginineAmino AcidMouse, rat, hamsterKlauss et al.
Saloman et al.
Mizunuma et al. 1984
Zhang et al. 2014
Wang et al. 2016
Toma et al. 2000
Dawra et al. 2006
Delaney et al. 1993
L-lysineAmino AcidRatAcute pancreatitisBiczo et al. 2011
L-ornithineAmino AcidRatBiczo et al. 2010
Chemical (bile) Models
Model TypeTargetClassAcute/Chronic
DBTC (IV)chemical (bile)Mouse, rat, hamster, rabbit, dog, cat, pig
TNBS (intraductal)chemical (bile)Mouse, rat, hamster, rabbit, dog, cat, pig
Mechanical Models
Model TypeTargetClassAcute/Chronic
Ligation/obstructionMechanicalMouse, rat, hamster, rabbit, dog, opossum, cat, pig
Vacular/IschemiaMechanicalMouse, rat, hamster, rabbit, dog, opossum, cat, pig
Autoimmune Models
Model TypeTargetClassAcute/Chronic
InfectiousAutoimmuneMouse, rabbit, goat
ImmuneAutoimmuneRat, rabbit
Patient Derived Models
Model TypeTargetClassAcute/Chronic
CFTR mutated PDX organoidsPatient derived modelsCFTROrganoids
Patient derived IPSCs- AcinarPatient derived modelsOrganoids
Herbert’s AgarosePatient derived modelsOrganoids
Nongenic Mouse Models
Model TypeTargetClassAcute/Chronic
Pancreatic duct ligationNongenic mouse modelPancreatic ductMouseAcute pancreatitis,
chronic pancreatitis (partial ligation)
Bile acid infusion modelNongenic mouse modelMouseAcute pancreatitis
Miscellaneous Models
Model TypeTargetClassAcute/Chronic
ETOH +HFD chronic (10 week)Alcohol induced

Environmental modulators
Mouse, rat, hamster
Model TypeTargetClassAcute/Chronic
Post ERCPPost ERCPMouse, rat
Model TypeTargetClassAcute/Chronic
Cat modelsOtherNon-rodent
Dog modelsOtherNon-rodent
Pig modelsOtherNon-rodent

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