Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Drug: Mesalazine

• Registration Number: NCT02077777
• Lead Sponsor: SOFAR S.p.A.

Brief Summary

The purpose of this study is to obtain an "in vivo" confirmation that mesalazine induces the gene expression of μ-protocadherin and other related genes in the colon mucosa, as demonstrated in some "in vitro" experiments. .

Detailed Description

Pilot Trial, single-blind, parallel group on biopsy specimens of healthy colon mucosa in patients with precancerous lesions of the colon and rectum (adenomas) treated with mesalazine.

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2014-02-28
• Study First Submitted QC: 2014-02-28
• Study First Posted: 2014-03-04
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-01
• Last Update Posted: 2016-12-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Patients with precancerous colorectal lesions (polypoid or nonpolypoid adenomas) that needs of an endoscopic exam of control after 3 months from the removal of the lesions (determined on the basis of the morphological and histological characteristics of the lesions and of the removal technique)
• Ability and willingness to adhere to study regimen
• Written informed consent

The following inclusion criteria was deleted according to Amendment n. 01 approved by the Ethical Committee on 19/dec/2014:

• diverticular disease/diverticular colitis;

The rationale of this change is that the presence of diverticular disease/diverticular colitis does not contribute to the definition of the trial primary end-points and represents a critical point during the patient selection with an impact on duration and conduction of the study.

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Exclusion Criteria

• Patients under therapy with Aspirin (>100 mg/die) or other FANS
• Inflammatory bowel disease (IBD)
• Hypersensitivity to Mesalazine.
• Pregnant or nursing (lactating) women
• Patients who belonging to the category n. 4 of the ASA physical status classification system
• contraindications to mesalazine therapy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
5-ASA	Mesalazine	Mesalazine 800 mg orally t.i.d for 3 months

Primary Outcome Measures

Name	Time	Method
Molecular analysis of gene expression levels of μ-protocadherin and other related proteins	3 months	Molecular analysis (quantitative RT-PCR) of gene expression levels of μ-protocadherin, protocadherin 19, protocadherin 24, cadherin E, TCF7L2, TCF4, c-myc, Cyclin D1, p21waf1, VEGF, CD44, Met, KLF4 e CEBP-α and comparison of the levels assessed at the end of the treatment period with the baseline.

Secondary Outcome Measures

Name	Time	Method
Evaluation of protein expression level of μ-protocadherin, Ki-67, Caspase-3 and Histone H2AXγ, evaluation of DNA oxidative damage and intra-mucosal concentration of 5-Acetylsalicylic acid	3 months	These parameters will be examined using molecular analysis of the oxidation and depurination levels of the DNA and chromatographic analysis of the intra-mucosal concentration of 5-Acetylsalicylic acid, in biopsies of normal mucosa of the colon taken before and after the treatment of patients with 5-Acetylsalicylic acid: * quantification of the percentage of cells expressing the following proteins by immunohistochemical analysis: μ-protocadherin, Ki-67, Caspase-3 and Histone H2AXγ; * quantification of number of AP sites per 100000 DNA bp; * quantification of nanograms di 8-OhdG (8-hydroxyguanine) per micrograms of DNA

Trial Locations

Locations (1)

Istituti Ospitalieri di Cremona; 🇮🇹 Cremona, Italy