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

NCT02077777 | Completed Phase 2

• 1 other identifier: MES-CT 01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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. .

Conditions

Colorectal Cancer

Keywords

mesalazine; colon; cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 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

Study Arms (2)

5-ASA

EXPERIMENTAL

Mesalazine 800 mg orally t.i.d for 3 months

Drug: Mesalazine

No treatment

NO INTERVENTION

no treatment

Interventions

Mesalazine DRUG

Mesalazine cpr 800 mg t.i.d. for 3 months

Also known as: 5-aminosalicylic acid, 5-ASA, Pentacol

5-ASA

Eligibility Criteria

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

You may qualify if:

• 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
• \- 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• SOFAR S.p.A.: lead

Study Sites (1)

Istituti Ospitalieri di Cremona

Cremona, Cremona, 26100, Italy

Location

Related Publications (7)

• Parenti S, Ferrarini F, Zini R, Montanari M, Losi L, Canovi B, Ferrari S, Grande A. Mesalazine inhibits the beta-catenin signalling pathway acting through the upregulation of mu-protocadherin gene in colo-rectal cancer cells. Aliment Pharmacol Ther. 2010 Jan;31(1):108-19. doi: 10.1111/j.1365-2036.2009.04149.x.

  PMID: 19785626 BACKGROUND

• Losi L, Parenti S, Ferrarini F, Rivasi F, Gavioli M, Natalini G, Ferrari S, Grande A. Down-regulation of mu-protocadherin expression is a common event in colorectal carcinogenesis. Hum Pathol. 2011 Jul;42(7):960-71. doi: 10.1016/j.humpath.2010.10.009. Epub 2011 Mar 2.

  PMID: 21315419 BACKGROUND

• Brown JB, Lee G, Managlia E, Grimm GR, Dirisina R, Goretsky T, Cheresh P, Blatner NR, Khazaie K, Yang GY, Li L, Barrett TA. Mesalamine inhibits epithelial beta-catenin activation in chronic ulcerative colitis. Gastroenterology. 2010 Feb;138(2):595-605, 605.e1-3. doi: 10.1053/j.gastro.2009.10.038. Epub 2009 Oct 29.

  PMID: 19879273 BACKGROUND

• Velayos FS, Terdiman JP, Walsh JM. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol. 2005 Jun;100(6):1345-53. doi: 10.1111/j.1572-0241.2005.41442.x.

  PMID: 15929768 BACKGROUND

• Lyakhovich A, Gasche C. Systematic review: molecular chemoprevention of colorectal malignancy by mesalazine. Aliment Pharmacol Ther. 2010 Jan 15;31(2):202-9. doi: 10.1111/j.1365-2036.2009.04195.x. Epub 2009 Nov 5.

  PMID: 19891667 BACKGROUND

• Gushima M, Hirahashi M, Matsumoto T, Fujita K, Fujisawa R, Mizumoto K, Nakabeppu Y, Iida M, Yao T, Tsuneyoshi M. Altered expression of MUTYH and an increase in 8-hydroxydeoxyguanosine are early events in ulcerative colitis-associated carcinogenesis. J Pathol. 2009 Sep;219(1):77-86. doi: 10.1002/path.2570.

  PMID: 19479711 BACKGROUND

• Obtulowicz T, Swoboda M, Speina E, Gackowski D, Rozalski R, Siomek A, Janik J, Janowska B, Ciesla JM, Jawien A, Banaszkiewicz Z, Guz J, Dziaman T, Szpila A, Olinski R, Tudek B. Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. Mutagenesis. 2010 Sep;25(5):463-71. doi: 10.1093/mutage/geq028. Epub 2010 Jun 9.

  PMID: 20534734 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

Mesalamine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Aminosalicylic Acids; Salicylates; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols

Study Officials

• Federico Buffoli, Doctor

  Istituti Ospitalieri di Cremona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 4, 2014
• Study Start: October 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 2, 2016

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)