Prophylactic Tributyrin Supplementation in Acute Pancreatitis; a Phase IIa (Proof of Concept) Double-blind Randomized Placebo-controlled Food Supplement Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 92
- 试验地点
- 4
- 主要终点
- Plasma endotoxin levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Plasma endotoxin levels
时间窗: Measured 3 days after randomisation
Plasma endotoxin levels
次要结局
- Length of hospital and/or ICU stay(During the whole study period including follow-up of 90 days)
- Infectious complications(During the whole study period including follow-up of 90 days)
- Systemic inflammatory response parameters (SIRS): respiratory rate(During the initial admission)
- Systemic inflammatory response parameters (SIRS): white blood cell count(During the initial admission)
- (Peri-)pancreatic necrosis(During the whole study period including follow-up of 90 days)
- Mortality(During the whole study period including follow-up of 90 days)
- Readmissions(During the whole study period including follow-up of 90 days)
- Systemic inflammatory response parameters (SIRS): temperature(During the initial admission)
- Endocrine insufficiency(During the whole study period including follow-up of 90 days)
- (New onset) transient/persistant (multiple) organ failure(During the whole study period including follow-up of 90 days)
- Disease severity according to the revised Atlanta Classification(During the whole study period including follow-up of 90 days)
- The need (and number of) for surgical, endoscopic or radiologic interventions(During the whole study period including follow-up of 90 days)
- Exocrine insufficiency(During the whole study period including follow-up of 90 days)
- Fecal and saliva microbiota and fecal metabolomics (i.e., SCFAs) analysis(During the whole study period including follow-up of 90 days)
- Systemic inflammatory response parameters (SIRS): pulse(During the initial admission)
研究者
HC van Santvoort
dr. prof.
St. Antonius Hospital