Clinical trial NCT06508502: Pancreatitis - Microbiome as Predictor of Severity II
Official title: Pancreatitis - Microbiome as Predictor of Severity II
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Pancreatitis
Acute Pancreatitis With Infected Necrosis
Keywords: Pancreatitis
Microbiome
Lead sponsor: University Medical Center Goettingen
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with acute pancreatitis within 48h after hospital admission. Acute pancreatitis is defined if 2 of the following criteria are fullfilled.

1. Lipase \> 3x the upper limit
2. Typical abdominal pain (belt-like upper abdominal pain)
3. Characteristic CT findings

Brief summary: 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.

Detailed description: 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.

1. Buccal and rectal swabs, stool and plasma will be obtained to analyze the orointestinal microbiome and microbial derived metabolites.
2. Centers from different continents with different ethical background and dietary habits will enroll patients to gain a more generalizable microbial profile.
3. Microbial shifts were observed between severe AP (RAC 3) and mild/ moderate severe (RAC 1+2).
4. 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.

Eligibility criteria: Inclusion Criteria:

* Patients with initial diagnosis (\< 48h) of acute pancreatitis
* Age ≥ 18 years
* Patients able to understand/ give their written consent

Exclusion Criteria:

* Recurrent acute pancreatitis (\>2 previous episodes)
* Clinical or imaging signs of chronic pancreatitis
* Referred patients with length of hospital stay \> 48h

Primary outcomes:
measure: Novel microbiome species and/or functional metabolic pathways that are associated with the severity of acute pancreatitis
timeFrame: until discharge (up to 90 days)
measure: Classifier developed based on differentially regulated metabolites
timeFrame: Until discharge (up to 90 days)
Secondary outcomes:
measure: Mortality
timeFrame: up to 90 days
measure: Length of hospital stay
timeFrame: up to 90 days
measure: Post-discharge exocrine and endocrine insufficiency
timeFrame: up to 90 days
measure: Post-discharge re-intervention
timeFrame: up to 365 days
measure: Recurrent/chronic pancreatitis rate
timeFrame: up to 365 days
measure: Volatile organic compounds
timeFrame: up to 365 days
Other outcomes:
Locations:
city: Göttingen
country: Germany
facility: University Medical Center Goettingen
state: Lower Saxony
Study officials:
References:
citation: Capurso G, Ponz de Leon Pisani R, Lauri G, Archibugi L, Hegyi P, Papachristou GI, Pandanaboyana S, Maisonneuve P, Arcidiacono PG, de-Madaria E. Clinical usefulness of scoring systems to predict severe acute pancreatitis: A systematic review and meta-analysis with pre and post-test probability assessment. United European Gastroenterol J. 2023 Nov;11(9):825-836. doi: 10.1002/ueg2.12464. Epub 2023 Sep 27.
citation: Ammer-Herrmenau C, Antweiler KL, Asendorf T, Beyer G, Buchholz SM, Cameron S, Capurso G, Damm M, Dang L, Frost F, Gomes A, Hamm J, Henker R, Hoffmeister A, Meinhardt C, Nawacki L, Nunes V, Panyko A, Pardo C, Phillip V, Pukitis A, Rasch S, Riekstina D, Rinja E, Ruiz-Rebollo ML, Sirtl S, Weingarten M, Sandru V, Woitalla J, Ellenrieder V, Neesse A. Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis. Gut. 2024 Feb 23;73(3):485-495. doi: 10.1136/gutjnl-2023-330987.
citation: Ammer-Herrmenau C, Neesse A. Response to: short-chain fatty acids in patients with severe acute pancreatitis: friend or foe? Gut. 2024 Nov 11;73(12):e39. doi: 10.1136/gutjnl-2024-332236. No abstract available.
citation: van den Berg FF, Besselink MG, van Santvoort H. Short-chain fatty acids in patients with severe acute pancreatitis: friend or foe? Gut. 2024 Nov 11;73(12):e34. doi: 10.1136/gutjnl-2024-332129. No abstract available.
citation: Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM, Nieuwenhuijs VB, Bollen TL, van Ramshorst B, Witteman BJ, Rosman C, Ploeg RJ, Brink MA, Schaapherder AF, Dejong CH, Wahab PJ, van Laarhoven CJ, van der Harst E, van Eijck CH, Cuesta MA, Akkermans LM, Gooszen HG; Dutch Acute Pancreatitis Study Group. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Feb 23;371(9613):651-659. doi: 10.1016/S0140-6736(08)60207-X. Epub 2008 Feb 14.
citation: Beyer G, Hoffmeister A, Michl P, Gress TM, Huber W, Algul H, Neesse A, Meining A, Seufferlein TW, Rosendahl J, Kahl S, Keller J, Werner J, Friess H, Bufler P, Lohr MJ, Schneider A, Lynen Jansen P, Esposito I, Grenacher L, Mossner J, Lerch MM, Mayerle J; Collaborators:. S3-Leitlinie Pankreatitis - Leitlinie der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) - September 2021 - AWMF Registernummer 021-003. Z Gastroenterol. 2022 Mar;60(3):419-521. doi: 10.1055/a-1735-3864. Epub 2022 Mar 9. No abstract available. German.
citation: Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013 Sep;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218. Epub 2013 Jul 30.