Probiotic After Acute Colonic Diverticulitis

Probiotic EcN in Symptomatic Patients After an Episode of Acute Colonic Diverticulitis: a Prospective Multicentre Observational Study.

The goal of this observational study is to assess the efficacy and safety of the probiotic Escherichia coli Nissle 1917 (EcN®, Ca.Di.Group S.p.A) in the treatment of symptomatic patients after an episode of both complicated and uncomplicated acute colonic diverticulitis.

The main question it aims to answer are:

• Is the studied probiotic able to significantly reduce symptoms, assessed by means of a validated and dedicated score?
• Is there any difference in microbiota among the study group at baseline and a selected cohort of patients subdivided in subjects with diverticulosis and asymptomatic subjects after an episode of acute uncomplicated diverticulitis or an episode of complicated diverticulitis submitted to surgery with colonic resection without stoma?
• Is there any difference in microbiota in the study group at baseline and after 3 and 6 months of treatment with the probiotic?
• Is there any correlation between microbiota modification and symptoms during follow-up?
• Is there any impact on fecal calprotectin values before and during probiotic therapy?
• Is there any modification of evacuation before and during follow-up?
• Is probiotic able to prevent recurrent episodes of acute diverticulitis during follow-up?
• The safety of the probiotic will be assessed during the follow-up. The study group will be assessed at baseline and during follow-up with a dedicated clinical score and Bristol stool scale. Microbiota and fecal calprotectin values will be also assessed at baseline and during follow-up. Microbiota at baseline will be also evaluated for comparison in the three selected groups with diverticulosis and both asymptomatic and symptomatic after an episode of acute diverticulitis.

Study Overview

• Status: Recruiting
• Conditions: Therapy; Diverticulitis, Colonic
• Intervention / Treatment: Drug: Probiotic Formula

• Study Type: Observational
• Enrollment (Estimated): 145

Contacts and Locations

• Study Contact: Name: Antonio Tursi, MD, PhD; Phone Number: +393473490583; Email: antotursi@tiscali.it
• Study Contact Backup: Name: Marcello Picchio, MD; Phone Number: +393392371293; Email: marcellopicchio@libero.it

Study Locations

• Italy
  • Andria, Italy, 76123
    • Recruiting
    • Gastroenterology Service , ASL BAT,
    • Contact: Antonio Tursi, MD; Email: antotursi@tiscali.it
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • Recruiting
      • UOC di Gastroenterologia ed Endoscopia Digestiva, Ospedale "Pugliese-Ciaccio
      • Contact: Stefano Rodinò, MD, PhD; Email: srodino@tin.it
  • Lazio
    • Latina, Lazio, Italy, 04100
      • Recruiting
      • UOSVD di Endoscopia Digestiva, Ospedale "S. Maria Goretti"
      • Contact: Giuseppe Pianese; Email: pianesepino@libero.it
    • Roma, Lazio, Italy, 00152
      • Recruiting
      • UOC di Gastroenterologia, Azienda Ospedaliera "S. Camillo-Forlanini"
      • Contact: Roberto Faggiani, MD, PhD; Email: faggiani.r@tin.it
    • Roma, Lazio, Italy, 00161
      • Recruiting
      • UOSVD di Gastroenterologia ed Endoscopia Digestiva, Ospedale "Umberto I"
      • Contact: Antonio Cuomo, MD, PhD; Email: drcuomo@iol.it
    • Roma, Lazio, Italy, 00167
      • Recruiting
      • UOC di Medicina Interna e Gastroenterologia, Ospedale "Cristo Re"
      • Contact: Giovanni Brandimarte, MD, PhD; Email: giovannibrandimarte56@gmail.com
    • Velletri, Lazio, Italy, 00049
      • Recruiting
      • UOC Chirurgia Generale, Ospedale "P. Colombo"
      • Contact: Marcello Picchio, MD; Email: marcellopicchio@libero.it
    • Viterbo, Lazio, Italy, 01100
      • Recruiting
      • UOC di Gastroenterologia, Ospedale "Belcolle",
      • Contact: Costantino Zampaletta; Email: zcosta@libero.it
  • Lombardia
    • Milan, Lombardia, Italy, 20132
      • Recruiting
      • • UOC di Gastroenterologia ed Endoscopia Digestiva, Ospedale Universitario "San Raffaele"
      • Contact: Silvio Danese, MD, PhD; Email: sdanese@hotmail.com
    • Padova, Lombardia, Italy, 35031
      • Recruiting
      • UOC di Gastroenterologia Azienda Ospedaliero-Universitaria di Padova
      • Contact: Edoardo V. Savarino, MD, PhD; Email: edoardo.savarino@unipd.it
    • Piacenza, Lombardia, Italy, 29121
      • Recruiting
      • UOC di Gastroenterologia, Ospedale "Guglielmo da Saliceto"
      • Contact: Giovanni Aragona, MD, PhD; Email: g.aragona@ausl.pc.it
  • Marche
    • Pesaro, Marche, Italy, 61121
      • Recruiting
      • UOC di Gastroenterologia, Ospedale "S. Salvatore",
      • Contact: Antonella Scarcelli, MD; Email: antonella.scarcelli@ospedalimarchenord.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include the above specified study groups.

Description

Inclusion Criteria:

• Symptomatic patients three months after an episode of uncomplicated acute colonic diverticulitis;
• Symptomatic patients six months after an episode of complicated acute colonic diverticulitis; submitted to .surgical colonic resection without stoma;
• Patients with diverticulosis;
• Asymptomatic patients three months after an episode of uncomplicated acute colonic diverticulitis;
• Asymptomatic patients six months after an episode of complicated acute colonic diverticulitis; submitted to surgical colonic resection without stoma.

Exclusion Criteria:

• Ongoing acute diverticulitis at radiologic assessment
• Antibiotic therapy, both systemic and topic, and/or probiotics and/or mesalazine within four weeks before enrolment;
• Lactulose-lactitol use within four weeks before enrolment;
• Presence of chronic inflammatory bowel diseases;
• Presence of Segmental Colitis Associated with Diverticulitis (SCAD);
• Presence of ischemic colitis;
• Severe chronic liver (Child-Pugh C) and/or pancreatic and/or renal diseases;
• Patients with severe renal failure;
• Presence of suspected/actual pregnancy;
• Presence of recent/ongoing neoplasia, under oncological treatment within 6 months before enrolment;
• Presence of COVID-19 infection;
• Patients unable to give informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symptomatic patients after acute diverticulitis; Patients aged ≥18 with persistent symptoms at least three months after a radiologic and/or endoscopic documented acute diverticulitis or after six months of surgery for complicated acute diverticulitis. Therapy with Escherichia coli Nissle 1917 (EcN®) will be prescribed for a global duration of six months with the following assumption schedule: 2 capsules b.i.d. during 4 weeks, followed by 1 capsule o.i.d during 20 days each month for 5 months.	Drug: Probiotic Formula; Capsule with 25 billion live strains of Escherichia coli Nissle 1917; Other Names: Escherichia coli Nissle 1917
Diverticulosis; Patients with asymptomatic diverticulosis. No therapy will be administered. Microbiota assessment will be performed.
Asymptomatic patients after acute uncomplicated diverticulitis; Asymptomatic patients assessed three months after an episode of acute uncomplicated diverticulitis. No therapy will be administered. Microbiota assessment will be performed.
Asymptomatic patients after acute complicated diverticulitis; Asymptomatic patients assessed six months after an episode of acute complicated diverticulitis submitted to surgery with resection and without stoma . No therapy will be administered. Microbiota assessment will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median symptomatic score reduction after therapy with Escherichia coli Nissle 1917	Median symptomatic score assessed at baseline and during follow-up	Six-months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota qualitative composition	Composition of microbiota will be assessed in all the study groups with a dedicated kit for collection.	Baseline
Microbiota qualitative composition modification	Composition of microbiota will be assessed in symptomatic study groups with a dedicated kit for collection.	Baseline and during 6-month follow-up.
Microbiota qualitative composition and median symptomatic score correlation	Correlation between the median symptomatic score and qualitative composition of microbiota modification after therapy.	Baseline and during 6-month follow-up.
Concentration of fecal calprotectin	Assessment of fecal calprotectin concentration in the symptomatic study group.	Baseline and during 6-month follow-up.
Bristol stool scale modification	Assessment of median Bristol stool scale in the symptomatic study group.	Baseline and during 6-month follow-up.
Prevention of recurrent acute diverticulitis	Number off patients with recurrent acute diverticulitis.	Six-month follow-up.
Safety	Number of patients with adverse events.	Six-month follow-up.

Collaborators and Investigators

• Sponsor: Erasmo Spaziani
• Investigators: Principal Investigator: Walter Elisei, MD, • UOC di Gastroenterologia, Azienda Ospedaliera "S. Camillo-Forlanini", Roma

Publications and helpful links

General Publications

• Kvasnovsky CL, Adams K, Papagrigoriadis S. Diverticular disease as a chronic gastrointestinal condition: experience from a specialist clinic. Eur J Gastroenterol Hepatol. 2015 Apr;27(4):442-8. doi: 10.1097/MEG.0000000000000304.
• Mj O, Turner GA, A S, Frizelle FA, R P. Distinct changes in the colonic microbiome associated with acute diverticulitis. Colorectal Dis. 2022 Dec;24(12):1591-1601. doi: 10.1111/codi.16271. Epub 2022 Aug 11.
• Tursi A, Papa V, Lopetuso LR, Settanni CR, Gasbarrini A, Papa A. Microbiota Composition in Diverticular Disease: Implications for Therapy. Int J Mol Sci. 2022 Nov 26;23(23):14799. doi: 10.3390/ijms232314799.
• Teng G, Liu Z, Liu Y, Wu T, Dai Y, Wang H, Wang W. Probiotic Escherichia coli Nissle 1917 Expressing Elafin Protects Against Inflammation and Restores the Gut Microbiota. Front Microbiol. 2022 May 6;13:819336. doi: 10.3389/fmicb.2022.819336. eCollection 2022.
• Lahat A, Fidder HH, Ben-Horin S. Development and validation of a diverticular clinical score for symptomatic uncomplicated diverticular disease after acute diverticulitis in a prospective patient cohort. Therap Adv Gastroenterol. 2020 May 8;13:1756284820913210. doi: 10.1177/1756284820913210. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: September 10, 2023
• First Submitted That Met QC Criteria: September 10, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 10, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Diverticular Diseases; Diverticulosis, Colonic; Diverticulitis; Diverticulitis, Colonic
• Other Study ID Numbers: EcN2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No