Prophylactic Tributyrin Supplementation in Acute Pancreatitis (PARROT)

St. Antonius Hospital

Status and phase: Enrolling; Phase 2

Conditions: Acute Pancreatitis

Treatments: Dietary Supplement: Micro-encapsulated granules of tributyrin (intervention); Dietary Supplement: Micro-encapsulated granules of sunflower oil (placebo)

Study type: Interventional

Funder types: Other

Identifiers

NCT06147635

NL81496.100.22

Details and patient eligibility

About

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.

Full 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).

Enrollment: 92 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

92 participants in 2 patient groups, including a placebo group

Intervention group

Experimental group

Description:

Micro-encapsulated tributyrin granules, 4 grams three times daily, for a maximum of 14 days

Treatment:

Dietary Supplement: Micro-encapsulated granules of tributyrin (intervention)

Control group

Placebo Comparator group

Description:

Micro-encapsulated sunflower oil granules, 4 grams three times daily, for a maximum of 14 days

Treatment:

Dietary Supplement: Micro-encapsulated granules of sunflower oil (placebo)