Primary: To evaluate the ability to culture PDEC organoids from pancreatic duct biopsies. Secondary: (i) To evaluate ion transport in PDEC organoids derived from pancreatitis patients. (ii) To evaluate the ability of duodenal organoids to mimic ion…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Assess the ability to culture PDEC organoids from pancreatic duct
microbiopsies, to study the pathophysiology and pharmacotherapy of pancreatitis
in vitro.
Secondary outcome
• Asses the phenotype of PDEC organoids derived from pancreatitis patients, as
compared to those derived from non-pancreatitis patients, by investigation of:
o Genetic makeup
o Gene and protein expression
o Ion transport
o Response to known pancreatitis-inducers and/or ion transport modulators, to
further elucidate the molecular mechanisms involved in the disruption of CFTR
function in PDECs in pancreatitis and potentially to advance the development of
pharmacotherapy for pancreatitis.
• Assess the ability of duodenal organoids to mimic key features of ion
transport in PDEC organoids, to explore a more readily accessible surrogate
model to study the pathophysiology and pharmacotherapy of pancreatitis in vitro.
Background summary
Pancreatitis is a common cause of hospitalization, with no specific therapy
available currently. Dysfunction of the cystic fibrosis transmembrane
conductance regulator (CFTR) and/or insufficiency of electrolyte and fluid
secretion by pancreatic ductal epithelial cells (PDECs) is associated with
pancreatitis. CFTR modulators might increase CFTR levels and/or function in
PDECs and may ameliorate pancreatitis. However, current human PDEC model
systems have limited success in establishment and expansion and require an
invasive sample collection. A human model system to study electrolyte and fluid
secretion in pancreatitis patients is missing. We hypothesize that pancreatic
duct biopsies can be grown into organoids and expanded long enough to perform
short circuit current measurements, and that duodenal organoids can be used as
a surrogate model to study CFTR in pancreatitis patients.
Study objective
Primary: To evaluate the ability to culture PDEC organoids from pancreatic duct
biopsies. Secondary: (i) To evaluate ion transport in PDEC organoids derived
from pancreatitis patients. (ii) To evaluate the ability of duodenal organoids
to mimic ion transport in PDEC organoids derived from pancreatitis patients.
Study design
Pancreatic duct and duodenal biopsies will be obtained from pancreatitis
patients and grown into organoids, which will be phenotyped and stored in a
biobank for further investigation.
Study burden and risks
Patients undergoing pancreatoscopy will receive a single blood collection prior
to the procedure. In addition, 2 microbiopsies from the pancreatic duct and 2
biopsies from the duodenum will be taken during the procedure. There is no
extra burden, as these patients are undergoing the pancreatoscopy within the
framework of regular diagnostics and treatment. The risk of participation is
negligible, constituting marginal bleeding of the mucosa.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
A subject must meet all of the following criteria:
- Must be an adult (>18 years old)
- Must be undergoing pancreatoscopy within the framework of regular diagnostics
or treatment in the Erasmus MC
- Must sign informed written consent
Exclusion criteria
None
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL75856.078.21 |
| Other | NL9772 |