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 Domain | PROMs/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/Activities | PROMIS Short Form v2.0 – Social roles and activities |
| Nutrition/EPI | PEI-Q |
| Nutrition/EPI | Clinical measurements (weight, vitamins, etc) |
| AP Attacks/Flares | No 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.
GEMM Models
| Model Type | Target | Class | Chronic/Acute | ||
|---|---|---|---|---|---|
| mPRSS1 R122H | GEMM | PRSS1 | Mouse | Acute Pancreatitis | |
| hPRSS1 R122H /N291 | GEMM | PRSS1 | Mouse | Acute pancreatitis, chronic pancreatits | Athwal et al. 2014 |
| PRSS1 R122H | GEMM | PRSS1 | Mouse | Acute pancreatitis, chronic pancreatits | Huang et al. 2019 |
| PRRS2 and PRSS1 R122H | GEMM | PRSS2/PRSS1 | Mouse | Acute pancreatitis, chronic pancreatits | Wang et al. 2022 |
| PACE-Tryp(on) Ela-creERT;ratPRSSII (hereditary pancreatitis) | GEMM | Tryspin | Mouse | Acute pancreatitis | Gaiser et al. 2011 |
| Transgenic PRSS1R122H | GEMM | PRSS1 | Mouse | Acute pancreatitis (Cerulein induced) Chronic pancreatitis after 70 days of Cerulein tx | Gui et al. 2020 |
| The T7D23A mouse model | GEMM | Tryspin | Mouse | Acute pancreatitis (age 3-5 weeks) Chronic Pancreatitis (1 -2 months) | Geiz et al. 2018 |
| T7K24R mouse model | GEMM | Tryspin | Mouse | Acute pancreatitis (Cerulein induced) Chronic pancreatitis- Cerulein induced (2 days, sacrificed 3 or 10 days after last injection) | Jancso et al. 2020 |
| SPINK3 | GEMM | SPINK | Mouse | Acute Pancreatitis (Cerulein induced) | Ohmuraya et al. 2005 |
| IL-1B overexpressing | GEMM | IL-1b | Mouse | Chronic pancreatitis | Marrache F, et al. Gastroenterology 2008;135:1277–1287. |
| Atg5-knockout /deletion | GEMM | – | Mouse | – | Klauss et al. Saloman et al. Merry and Petrov |
| Atg7-knockout /deletion | GEMM | – | Mouse | – | Klauss et al. Merry and Petrov |
| IKKa knockout /deletion | GEMM | – | Mouse | – | Klauss et al. Saloman et al. |
| LAMP2 knockout/defficiency | GEMM | – | Mouse | – | Klauss et al. Saloman et al. Merry and Petrov |
| PERK knockout | GEMM | – | Mouse | – | Klauss et al. Saloman et al. Merry and Petrov |
| IKK2 Transgenic Overexpression | GEMM | – | Mouse | – | Klauss et al. |
| Mice lacking cilia in pancreatic cells | GEMM | – | Mouse | – | Klauss et al. |
| Kif3a deletion | GEMM | – | Mouse | – | Klauss et al. Saloman et al. Merry and Petrov |
| WBN/Kob | GEMM | – | Mouse | – | Klauss et al. Saloman et al. |
| Cpa1 pN256K | GEMM | – | Mouse | – | Merry and Petrov |
| Tgf-B1 Overexpression | GEMM | TGFb | Mouse | – | Merry and Petrov Sanvito et al. |
| CFTR– | GEMM | CFTR | Mouse | – | Durie et al. |
| PNLIPP p.T122M | GEMM | Pancreatic triglyceride lipase (PNLIP) | Mouse | Chronic pancreatitis | Zhu et al. 2023 |
| Ctrb 1-del | GEMM | CTRB1 | Mouse | Acute pancreatitis, chronic pancreatitis | Geisz, Jansco et al. 2019 |
Secretagogue Models
| Model Type | Target | Class | Chronic/Acute | References | |
|---|---|---|---|---|---|
| Cerulein: AP | Secretagogue | – | Mouse, rat, hamster, dog | Acute pancreatitis | Klauss et al. Saloman et al. Lampel et al. 1977 |
| Cerulein: RAP/CP | Secretagogue | – | Mouse, rat, hamster, dog | Chronic pancreatitis | Klauss et al. Saloman et al. |
| secretin, cholecystokinin-octapeptide, bombesin, and carbachol | Secretagogue | – | Guinea pig, hamster, rabbit | – | Padfield et al. 1989 Ali et al. 1990 |
Amino Acid Models
| Model Type | Target | Class | Acute/Chronic | References | |
|---|---|---|---|---|---|
| L-arginine | Amino Acid | – | Mouse, rat, hamster | – | Klauss 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-lysine | Amino Acid | – | Rat | Acute pancreatitis | Biczo et al. 2011 |
| L-ornithine | Amino Acid | – | Rat | – | Biczo et al. 2010 |
Chemical (bile) Models
| Model Type | Target | Class | Acute/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 Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| Ligation/obstruction | Mechanical | – | Mouse, rat, hamster, rabbit, dog, opossum, cat, pig | – |
| Vacular/Ischemia | Mechanical | – | Mouse, rat, hamster, rabbit, dog, opossum, cat, pig | – |
Autoimmune Models
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| Infectious | Autoimmune | – | Mouse, rabbit, goat | – |
| Immune | Autoimmune | – | Rat, rabbit | – |
Patient Derived Models
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| CFTR mutated PDX organoids | Patient derived models | CFTR | Organoids | – |
| Patient derived IPSCs- Acinar | Patient derived models | – | Organoids | – |
| Herbert’s Agarose | Patient derived models | – | Organoids | – |
Nongenic Mouse Models
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| Pancreatic duct ligation | Nongenic mouse model | Pancreatic duct | Mouse | Acute pancreatitis, chronic pancreatitis (partial ligation) |
| Bile acid infusion model | Nongenic mouse model | – | Mouse | Acute pancreatitis |
Miscellaneous Models
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| ETOH +HFD chronic (10 week) | Alcohol induced Environmental modulators | – | Mouse, rat, hamster | – |
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| Post ERCP | Post ERCP | – | Mouse, rat | – |
| Model Type | Target | Class | Acute/Chronic | |
|---|---|---|---|---|
| Cat models | Other | – | Non-rodent | – |
| Dog models | Other | – | Non-rodent | – |
| Pig models | Other | – | Non-rodent | – |
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