Microbiota and Immune microEnvironment in Pouchitis

NCT03136419 | Unknown

• 1 other identifier: MEP1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Microbiota and innate immunity in pouchitis: predisposing factors and modulation of the inflammation with probiotics. Around 20-25% of ulcerative colitis patients undergo restorative proctocolectomy with ileal pouch anal anastomosis. Pouchitis is an idiopathic inflammatory disease that may occur in ileal pouches. In our recent studies, we showed altered microbiota and innate immunity relationships in pouchitis. We plain to perform a double-blind, placebo-controlled trial probiotic therapy vs placebo starting at the time of ileostomy closure to evaluate the impact of microbiota that colonizes the pouch mucosa in the pathogenesis of pouchits, to determine how expression and activation status of the innate immunity system in different cell types and anatomical districts of pouch mucosa relate to microbiota population and follow-up the clinical outcome of anal pouches in light of microbiota-innate immune system interplay. Our study will include three phases:

1. 1.analysis of the intestinal microbiota with High Throughput Sequencing Unit and anaerobes cultures
2. 2.characterization of innate immunity with TLR, NLR, nicotinic receptors and LPMC analysis
3. 3.assessment of microbiota and innate immune system in the ileal pouch before ileostomy closure, 2 months after ileostomy closure and after 1 year follow up.

Conditions

Pouchitis; Ulcerative Colitis; Ileal Pouch

Keywords

microbiota; innate immunity

Outcome Measures

Primary Outcomes (1)

• quantification of inflammatory cytokines in the ileal mucosa levels by Bio-Plex cytokine immunoassay

  IL-1ß, IL-6, TNF-alpha

  8 weeks

Secondary Outcomes (7)

• quantify epithelial and leucocytes-derived anti-microbial defensins

  8 weeks

• pouchitis episodes

  12 months

• Relative abundance of bacterial phyla in faecal specimens

  8 weeks

• Systemic and local inflammatory status

  12 months

• Histological inflammatory severity

  8 weeks

Study Arms (2)

Control

PLACEBO COMPARATOR

Placebo capsules bis in die for 8 weeks

Dietary Supplement: Placebo

Experimental

EXPERIMENTAL

Lactobacillus casei DG capsules bis in die for 8 weeks

Dietary Supplement: Lactobacillus casei DG

Interventions

Lactobacillus casei DG DIETARY_SUPPLEMENT

Lactobacillus casei DG probiotic supplementation for 8 weeks

Experimental

Placebo DIETARY_SUPPLEMENT

Placebo supplementation for 8 weeks

Control

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with UC who will undergo restorative proctocolectomy with ileal pouch anal anastomosis and that will attend our outpatient's clinic for routine endoscopic and clinical follow-up.

You may not qualify if:

• Patients with cuffitis (inflammation of the rectal mucosa remnant) or Crohn's disease of the pouch (with perianal fistulae or with inflammation of the afferent ileal limb), as well as patients who will have received antibiotic or probiotic therapy during the previous 30 days will be excluded from the study.

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

Imerio Angriman

Padua, PD, 35128, Italy

RECRUITING

Related Publications (6)

• Angriman I, Scarpa M, Castagliuolo I. Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis. World J Gastroenterol. 2014 Aug 7;20(29):9665-74. doi: 10.3748/wjg.v20.i29.9665.

  PMID: 25110406 RESULT

• Scarpa M, Grillo A, Scarpa M, Brun P, Castoro C, Pozza A, Cavallo D, Faggian D, Ruffolo C, D'Inca R, Bardini R, Castagliuolo I, Angriman I. Innate immune environment in ileal pouch mucosa: alpha5 defensin up-regulation as predictor of chronic/relapsing pouchitis. J Gastrointest Surg. 2012 Jan;16(1):188-201; discussion 201-2. doi: 10.1007/s11605-011-1720-6. Epub 2011 Oct 8.

  PMID: 21983950 RESULT

• Scarpa M, Grillo A, Pozza A, Faggian D, Ruffolo C, Scarpa M, D'Inca R, Plebani M, Sturniolo GC, Castagliuolo I, Angriman I. TLR2 and TLR4 up-regulation and colonization of the ileal mucosa by Clostridiaceae spp. in chronic/relapsing pouchitis. J Surg Res. 2011 Aug;169(2):e145-54. doi: 10.1016/j.jss.2011.04.003. Epub 2011 May 5.

  PMID: 21601883 RESULT

• Scarpa M, Grillo A, Faggian D, Ruffolo C, Bonello E, D'Inca R, Scarpa M, Castagliuolo I, Angriman I. Relationship between mucosa-associated microbiota and inflammatory parameters in the ileal pouch after restorative proctocolectomy for ulcerative colitis. Surgery. 2011 Jul;150(1):56-67. doi: 10.1016/j.surg.2011.02.009. Epub 2011 May 5.

  PMID: 21549404 RESULT

• Scarpa M, Mescoli C, Rugge M, D'Inca R, Ruffolo C, Polese L, D'Amico DF, Sturniolo GC, Angriman I. Restorative proctocolectomy for inflammatory bowel disease: the Padova prognostic score for colitis in predicting long-term outcome and quality of life. Int J Colorectal Dis. 2009 Sep;24(9):1049-57. doi: 10.1007/s00384-009-0700-8. Epub 2009 Apr 22.

  PMID: 19415309 RESULT

• Angriman I, Scarpa M, Savarino E, Patuzzi I, Rigo A, Kotsafti A, Stepanyan A, Sciuto E, Celotto F, Negro S, Caruso A, Ruffolo C, Bardini R, Pucciarelli S, Barberio B, Spolverato G, Zingone F, D'Inca R, Castagliuolo I, Scarpa M. Oral administration of Lactobacillus casei DG(R) after ileostomy closure in restorative proctocolectomy: a randomized placebo-controlled trial (microbiota and immune microenvironment in pouchitis -MEP1). Gut Microbes. 2024 Jan-Dec;16(1):2423037. doi: 10.1080/19490976.2024.2423037. Epub 2024 Nov 1.

  PMID: 39485259 DERIVED

MeSH Terms

Conditions

Pouchitis; Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Ileitis; Enteritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Ileal Diseases; Colitis; Inflammatory Bowel Diseases; Colonic Diseases

Study Officials

• Imerio Angriman, MD

  University of Padova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Scarpa, MD

CONTACT

0039 3477245237; marcoscarpa73@yahoo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 5, 2017
• First Posted: May 2, 2017
• Study Start: October 31, 2016
• Primary Completion: October 31, 2018
• Study Completion: April 30, 2019
• Last Updated: May 2, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)