Prophylactic Tributyrin Supplementation in Acute Pancreatitis

NCT ID: NCT06147635

Last Updated: 2024-06-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-12
• Study Completion Date: 2027-01-31

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.

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).

Conditions

Acute Pancreatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention group

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

Group Type: EXPERIMENTAL

Micro-encapsulated granules of tributyrin (intervention)

Intervention Type: DIETARY_SUPPLEMENT

Three times daily 4 grams of micro-encapsulated granules of tributyrin, for a maximum of 14 days

Control group

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

Group Type: PLACEBO_COMPARATOR

Micro-encapsulated granules of sunflower oil (placebo)

Intervention Type: DIETARY_SUPPLEMENT

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

Interventions

Micro-encapsulated granules of tributyrin (intervention)

Three times daily 4 grams of micro-encapsulated granules of tributyrin, for a maximum of 14 days

Intervention Type: 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

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Antonius Hospital

OTHER

Sponsor Role: lead

Responsible Party

HC van Santvoort

dr. prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

H. C. van Santvoort, dr. prof.

Role: PRINCIPAL_INVESTIGATOR

St. Antonius Hospital

Locations

Reinier de Graaf Gasthuis

Delft, South Holland, Netherlands

Site Status: NOT_YET_RECRUITING

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Hannah Pauw, MD

Role: CONTACT

ha.pauw@antoniusziekenhuis.nl

0883207051 ext. +31

Facility Contacts

Rutger Quispel, dr. MD.

Role: primary

r.quispel@rdgg.nl

0152603089 ext. +31

Hjalmar C. van Santvoort, Prof. dr.

Role: primary

h.van.santvoort@antoniusziekenhuis.nl

0883201942 ext. +31

Hannah Pauw, drs.

Role: backup

ha.pauw@antoniusziekenhuis.nl

0623559868 ext. +31

Other Identifiers

NL81496.100.22

Identifier Type: -

Identifier Source: org_study_id