Back to resultsChemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Mesalazine
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring mesalazine, colon, cancer
Eligibility Criteria
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
Sites / Locations
- Istituti Ospitalieri di Cremona
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
5-ASA
No treatment
Arm Description
Mesalazine 800 mg orally t.i.d for 3 months
no treatment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02077777
Brief Title
Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SOFAR S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
mesalazine, colon, cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
5-ASA
Arm Type
Experimental
Arm Description
Mesalazine 800 mg orally t.i.d for 3 months
Arm Title
No treatment
Arm Type
No Intervention
Arm Description
no treatment
Intervention Type
Drug
Intervention Name(s)
Mesalazine
Other Intervention Name(s)
5-aminosalicylic acid, 5-ASA, Pentacol
Intervention Description
Mesalazine cpr 800 mg t.i.d. for 3 months
Primary Outcome Measure Information:
Title
Molecular analysis of gene expression levels of μ-protocadherin and other related proteins
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
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
Description
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
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Federico Buffoli, Doctor
Organizational Affiliation
Istituti Ospitalieri di Cremona
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituti Ospitalieri di Cremona
City
Cremona
ZIP/Postal Code
26100
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19785626
Citation
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.
Results Reference
background
PubMed Identifier
21315419
Citation
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.
Results Reference
background
PubMed Identifier
19879273
Citation
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.
Results Reference
background
PubMed Identifier
15929768
Citation
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.
Results Reference
background
PubMed Identifier
19891667
Citation
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.
Results Reference
background
PubMed Identifier
19479711
Citation
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.
Results Reference
background
PubMed Identifier
20534734
Citation
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.
Results Reference
background
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Chemopreventive Action of Mesalazine on Colorectal Cancer: a Pilot Study for an "in Vivo" Evaluation of the Molecular Effects on β-catenin Signaling Pathway.
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