Pancreatitis - Microbiome as Predictor of Severity II
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 700
- 试验地点
- 1
- 主要终点
- Novel microbiome species and/or functional metabolic pathways that are associated with the severity of acute pancreatitis
研究概览
简要总结
The goal of this observational study is to evaluate the orointestinal microbiome and microbial derived metabolome in patients suffering from acute pancreatitis as a biomarker for severity. The main questions it aims to answer are:
- Can the orointestinal microbiome robustly predict the course of acute pancreatitis?
- How does the microbiome impact the severity of an acute pancreatitis?
Buccal/ rectal swabs, plasma and stool is collected from patients with acute pancreatitis within 48h after hospital admission.
详细描述
Despite intensive research, early prediction of the course of acute pancreatitis (AP) is still not satisfactorily possible. Results of a European multicenter study showed that the intestinal microbiome is superior to established scores as a marker of severity in patients with AP. Hereby, a classifier was established using 16 differentially abundant rectal species and systemic inflammatory response syndrome (SIRS) and achieved an AUROC of 85%. Surprisingly, all species in the severe AP group were members of taxonomic families known for their short-chain fatty acid (SFCA) production. This observation contrasts with translational pancreatitis studies in mice. Based on these publications, a clinical trial is currently being initiated to treat severe AP with SCFA (NCT06147635). However, previous well-designed RCT that analyzed the effects of probiotics in predicted severe AP resulted in a worse outcome for patients in the probiotic arm. Consequently, national and international guidelines recommend against the usage of probiotics in AP.
Collectively, more research is needed to further elucidate the role of the oro-intestinal microbiota in the development of severe AP. To validate the results of previously mentioned multicenter study and to profoundly analyze the role of microbial metabolites and the fungeome, patients with AP will be prospectively recruited.
- Buccal and rectal swabs, stool and plasma will be obtained to analyze the orointestinal microbiome and microbial derived metabolites.
- Centers from different continents with different ethical background and dietary habits will enroll patients to gain a more generalizable microbial profile.
- Microbial shifts were observed between severe AP (RAC 3) and mild/ moderate severe (RAC 1+2).
- It is expected that the microbial compositions change during the inflammatory process upon early phase of pancreatitis. To minimize this microbial alternating effect a short time frame from hospital admission to recruitment (48h) is set.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients with initial diagnosis (< 48h) of acute pancreatitis
- •Age ≥ 18 years
- •Patients able to understand/ give their written consent
排除标准
- •Recurrent acute pancreatitis (>2 previous episodes)
- •Clinical or imaging signs of chronic pancreatitis
- •Referred patients with length of hospital stay > 48h
结局指标
主要结局
Novel microbiome species and/or functional metabolic pathways that are associated with the severity of acute pancreatitis
时间窗: until discharge (up to 90 days)
To assess the microbial diversity and differential abundances of species within buccal and rectal swabs analyzed by ONT sequencing followed by prediction of metabolic pathways and metabolites using tools such as Megan6 and GapSeq stratified by the Revised Atlanta Classification and severity (necrotic collections that require intervention and/or organ failure \>48h), adjusted for multiple individual confounders.
Classifier developed based on differentially regulated metabolites
时间窗: Until discharge (up to 90 days)
To assess the metabolite (predicted in 1. Primary endpoint) levels in stool and plasma samples by targeted metabolomics to develop a classifier based on differentially regulated metabolites to assess its discriminatory power in predicting Revised Atlanta Classification and severity.
次要结局
- Mortality(up to 1096 days (3 years))
- Length of hospital stay(up to 90 days)
- Post-discharge exocrine and endocrine insufficiency(up to 90 days)
- Post-discharge re-intervention(up to 1096 days (3 years))
- Recurrent/chronic pancreatitis rate(up to 1096 days (3 years))
- Volatile organic compounds(Until discharge (up to 90 days))
研究者
Christoph Ammer-Herrmenau
Dr.
University Medical Center Goettingen