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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Azione Chemiopreventiva Della Mesalazina Sul Cancro Del Colon-retto: Studio Pilota Per la Valutazione Degli Effetti Molecolari in Vivo Sulla Via di Segnalazione Proliferativa Della β-catenina (Official Title in Italian Language)

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Mesalazine


Participation Criteria
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Eligibility Criteria
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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. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-ASA<br>Mesalazine 800 mg orally t.i.d for 3 months | Drug: Mesalazine<br>* Mesalazine cpr 800 mg t.i.d. for 3 months<br>* Other names: Pentacol;|
| No Intervention: No treatment<br>no treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Molecular analysis of gene expression levels of μ-protocadherin and other related proteins | 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. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesalazine, colon, cancer