The main objective is to investigate the effect of oral tributyrin on plasma endotoxin in patients with acute pancreatitis.
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is plasma endotoxin concentration measured 3 days after
randomisation.
Secondary outcome
Secondary endpoints are toxicity, clinical outcomes, intestinal permeability,
fecal SCFA concentrations, intestinal microbiota composition and systemic
inflammatory response parameters (pulse, respiratory rate, temperature and
white blood cell count), response of peripheral blood mononuclear cells (PBMCs)
to stimulation with LPS, capacity of PBMCs to phagocytose/kill bacteria (E.
coli).
Background summary
Acute pancreatitis (AP) is a common gastrointestinal disorder requiring acute
hospitalization. Around 20% of patients that present with acute pancreatitis
eventually develop severe complications such as (multiple) organ failure,
(peri-) pancreatic necrosis, and secondary infections (i.e. infected necrosis,
bacteraemia, pneumonia). The gut, especially the gut microbiome, is likely to
play a role in development of infectious complications. Short-chain fatty
acids (SCFAs) produced by the gut microbiota, such as butyrate, are known
immunomodulators of the host response and exert local beneficial effects on the
gut barrier and microbiota. Currently, there are no safe and effective
therapies to mitigate disease severity that can be administered in the early
phase of pancreatitis. We hypothesize that orally administered tributyrin, a
pro-drug of butyrate, might beneficially influence disease progression in acute
pancreatitis and may be useful as prophylaxis.
Study objective
The main objective is to investigate the effect of oral tributyrin on plasma
endotoxin in patients with acute pancreatitis.
Study design
Phase IIa (Proof of concept) double-blind randomized placebo-controlled food
supplement trial.
Intervention
The intervention group receives three times daily 4g micro-encapsulated
granules of tributyrin and the control group receives three times daily an
equivalent volume of micro-encapsulated vegetable oil (i.e. placebo), for a
total of maximum 14 days.
Study burden and risks
The blood sampling at inclusion, and day 3 and 7 of treatment are preferably
combined with regular blood sampling. Participants may experience minor
discomfort from rectal swabs. Phase 1 studies with oral tributyrin conducted in
patients with solid tumors did not report serious adverse events. However,
there is a risk of unanticipated adverse events in our target population. An
independent data safety and monitoring board (DSMB) will discuss all reported
serious adverse events (SAE*s).
Koekoekslaan 1
Nieuwegein 3435CM
NL
Koekoekslaan 1
Nieuwegein 3435CM
NL
Listed location countries
Age
Inclusion criteria
acute pancreatitis, defined as two or more of the following criteria:
- abdominal pain
- serum amylas or lipase more than three times the upper limit
- evidence of acute pancreatitis on abdominal CT
Exclusion criteria
-Pancreatitis due to ERCP, malignancy, trauma
-Post-operative pancreatitis
-Intra-operative diagnosis
-Immunocompromised patients (history or current immunosuppressive treatment
such as chemotherapy, radiotherapy, longer use of immunosuppressive medication
or recent high doses, immunocompromised illness* such as AIDS, leukemia,
lymphoma)
-Pregnancy and/or lactation
-Age <18 years old
-History of chronic (MANNHEIM criteria) pancreatitis
- >72 hours since onset of symptoms
- Episode of acute pancreatitis within the last year, or a history of three or
more episodes of acute pancreatitis
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 | NL81496.100.22 |