Ulcerative Colitis Clinical Trial
— MEP1Official title:
Microbiota and Immune microEnvironment in Pouchitis: Randomized Controlled Trial Oral Administration of Lactobacillus Casei DG After Ileostomy Closure in Ileal Pouch Mucosa
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. analysis of the intestinal microbiota with High Throughput Sequencing Unit and
anaerobes cultures
2. characterization of innate immunity with TLR, NLR, nicotinic receptors and LPMC
analysis
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.
Status | Recruiting |
Enrollment | 32 |
Est. completion date | April 30, 2019 |
Est. primary completion date | October 31, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility |
Inclusion Criteria: 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. Exclusion Criteria: 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. |
Country | Name | City | State |
---|---|---|---|
Italy | Imerio Angriman | Padova | PD |
Lead Sponsor | Collaborator |
---|---|
University of Padova |
Italy,
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. Review. — View Citation
Scarpa M, Grillo A, Faggian D, Ruffolo C, Bonello E, D'Incà 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. — View Citation
Scarpa M, Grillo A, Pozza A, Faggian D, Ruffolo C, Scarpa M, D'Incà 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. — View Citation
Scarpa M, Grillo A, Scarpa M, Brun P, Castoro C, Pozza A, Cavallo D, Faggian D, Ruffolo C, D'Incà R, Bardini R, Castagliuolo I, Angriman I. Innate immune environment in ileal pouch mucosa: a5 defensin up-regulation as predictor of chronic/relapsing pouchi — View Citation
Scarpa M, Mescoli C, Rugge M, D'Incà 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 — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | quantification of inflammatory cytokines in the ileal mucosa levels by Bio-Plex cytokine immunoassay | IL-1ß, IL-6, TNF-alpha | 8 weeks | |
Secondary | quantify epithelial and leucocytes-derived anti-microbial defensins | Def2, Def3; DEFA5; DEFA6 by quantitative RT-PCR | 8 weeks | |
Secondary | pouchitis episodes | pouchitis episodes evaluated at PDAI >5 | 12 months | |
Secondary | Relative abundance of bacterial phyla in faecal specimens | Relative abundance of bacterial phyla in faecal specimens will be estimated by sequencing the PCR amplicons targeting 16S rRNA gene for the DNA samples extracted from each faecal specimen. | 8 weeks | |
Secondary | Systemic and local inflammatory status | Systemic and local inflammatory state will be assessed at each experimental timeline by: erythrocyte sedimentation rate (ESR), white blood cell count (WBC), platelets blood count (PLT), CRP and fecal lactoferrin | 12 months | |
Secondary | Histological inflammatory severity | Floren score | 8 weeks | |
Secondary | activation status of macrophages, dendritic cells, infiltrating lymphocytes | assessment of activation status of macrophages, dendritic cells, infiltratinglymphocytes evaluating surface markers (i.e.) and intracellular cytokines pattern (i.e. TNF , IFN , IL4, IL10) by cytofluorimetric analysis. | 8 weeks | |
Secondary | analysis of TLRs network | quantitative RT-PCR and immunohistochemistry | 8 weeks |
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