PARROT: Prophylactic Tributyrin Supplementation in Acute Pancreatitis
Study Details
Study Description
Brief Summary
The goal of this clinical trial is to investigate the possible effects of tributyrin supplementation in patients with a first episode of acute pancreatitis. The main question it aims to answer is:
• The effect of oral tributyrin supplementation on the plasma endotoxin level
Participants will be randomized between two groups: intervention and control group. They will receive:
- three times daily 4grams of micro-encapsulated granules of tributyrin, and the control group three times daily 4 grams of micro-encapsulated sunflower oil (i.e. placebo), for a total of 14 days
In total 92 adult patients with a first episode of acute pancreatitis will be included.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Rationale: 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.
Objective: The main objective is to investigate the effect of oral tributyrin on plasma endotoxin in patients with acute pancreatitis after 3 days of treatment.
Study design: Phase IIa (Proof of concept) double-blind randomized placebo-controlled food supplement trial.
Study population: 92 adult patients with a first episode of acute pancreatitis.
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.
Main study parameters/endpoints: The primary endpoint is plasma endotoxin concentration after 3 days of tributyrin treatment. Secondary endpoints include 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).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: 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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intervention group Micro-encapsulated tributyrin granules, 4 grams three times daily, for a maximum of 14 days |
Dietary Supplement: Micro-encapsulated granules of tributyrin (intervention)
Three times daily 4 grams of micro-encapsulated granules of tributyrin, for a maximum of 14 days
|
| Placebo Comparator: Control group Micro-encapsulated sunflower oil granules, 4 grams three times daily, for a maximum of 14 days |
Dietary Supplement: Micro-encapsulated granules of sunflower oil (placebo)
Three times daily 4 grams of micro-encapsulated granules of sunflower oil, for a maximum of 14 days
|
Outcome Measures
Primary Outcome Measures
- Plasma endotoxin levels [Measured 3 days after randomisation]
Plasma endotoxin levels
Secondary Outcome Measures
- Mortality [During the whole study period including follow-up of 90 days]
Occurence of death
- Infectious complications [During the whole study period including follow-up of 90 days]
The occurence of infected pancreatic necrosis, bacteremia, pneumonia, urosepsis, and/or infected ascites
- (New onset) transient/persistant (multiple) organ failure [During the whole study period including follow-up of 90 days]
The occurence of (new onset) transient/persistant (multiple) organ failure
- Disease severity according to the revised Atlanta Classification [During the whole study period including follow-up of 90 days]
Disease severity according to the revised Atlanta Classification
- (Peri-)pancreatic necrosis [During the whole study period including follow-up of 90 days]
The occurence of (peri)pancreatic necrosis
- Length of hospital and/or ICU stay [During the whole study period including follow-up of 90 days]
Measured in days
- The need (and number of) for surgical, endoscopic or radiologic interventions [During the whole study period including follow-up of 90 days]
The need (and number of) for surgical, endoscopic or radiologic interventions
- Fecal and saliva microbiota and fecal metabolomics (i.e., SCFAs) analysis [During the whole study period including follow-up of 90 days]
Fecal and saliva microbiota and fecal metabolomics (i.e., SCFAs) analysis
- Readmissions [During the whole study period including follow-up of 90 days]
The occurrence and number of readmissions
- Systemic inflammatory response parameters (SIRS): pulse [During the initial admission]
Pulse measured in beats per minute
- Systemic inflammatory response parameters (SIRS): respiratory rate [During the initial admission]
Respiratory rate measured in breaths per minute
- Systemic inflammatory response parameters (SIRS): temperature [During the initial admission]
Temperature measured in degrees celsius
- Systemic inflammatory response parameters (SIRS): white blood cell count [During the initial admission]
White blood cell count
- Exocrine insufficiency [During the whole study period including follow-up of 90 days]
Exocrine insufficiency
- Endocrine insufficiency [During the whole study period including follow-up of 90 days]
Endocrine insufficiency
Eligibility Criteria
Criteria
Inclusion Criteria:
-
First episode of acute pancreatitis (AP)
-
Able to read and/or understand the study procedures
-
Able to give informed consent (or their legal representatives)
-
<24 hours after diagnosis of AP
-
<72 hours after onset of symptoms of AP
Exclusion Criteria:
-
Pancreatitis due to endoscopic retrograde cholangiopancreatography (ERCP), malignancy or 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 recurrent or chronic (MANNHEIM criteria25) pancreatitis (see Appendix 15.1 for definition)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- St. Antonius Hospital
Investigators
- Principal Investigator: H. C. van Santvoort, dr. prof., St. Antonius Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL81496.100.22