Mesalazine Effects in Sporadic Colorectal Adenoma Patients
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Chemopreventive Effects of Mesalazine in Patients at High Risk of Recurrent (Nonfamilial) Colorectal Adenomas|
- Apoptotic index [ Time Frame: 6 months ] [ Designated as safety issue: No ]Change in apoptotic index after treatment with mesalazine as compared to placebo
- Proliferation index [ Time Frame: 6 months ] [ Designated as safety issue: No ]Change in proliferation index and distribution of proliferating cells in crypts after treatment with mesalazine as compared to placebo
- Expression of β-catenin signaling pathway [ Time Frame: 6 months ] [ Designated as safety issue: No ]Change in expression of β-catenin signaling pathway components after treatment with mesalazine as compared to placebo
|Study Start Date:||July 2012|
|Study Completion Date:||June 2015|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Mesalazine, 3 grams once daily for six months
Mesalazine 3 grams, once daily for six months
Placebo Comparator: Placebo
Placebo, 3 grams, once daily for six months
Placebo 3 grams, once daily for six months
Rationale: Patients with sporadic colorectal adenomatous polyps removed by polypectomy have a high rate of polyp recurrence and carry an increased risk for the development of colorectal carcinoma (CRC). Chemoprevention may lower the rate of adenoma recurrence after polypectomy, thereby reducing the risk of development or death from CRC. Mesalazine is an attractive candidate for chemoprevention, since even during long-term use it has only limited systemic adverse effects and no gastrointestinal toxicity. In a prospective trial a trend towards reduced adenoma recurrence has been observed in high risk patients with a history of at least 3 sporadic colorectal adenomas treated with mesalazine. Identification of biologically relevant antineoplastic properties of mesalazine in patients with sporadic adenomatous polyps will support further investigation of mesalazine as chemopreventive agent against colorectal neoplasia in the sporadic setting. Growth inhibition of colonic epithelial cells through induction of apoptosis and inhibition of proliferation is widely recognized as a potential mechanism for chemoprevention of colorectal cancer. In vivo data suggest that mesalazine exerts pro-apoptotic and anti-proliferative effects on normal colorectal epithelial cells. Furthermore, there is in vitro evidence in CRC cells that mesalazine inhibits Wnt/beta-catenin signalling, an early and common inappropriately activated pathway in colorectal carcinogenesis and molecular target for chemoprevention.
Objective: Evaluate the effects of mesalazine therapy on histologically normal sigmoid and rectal mucosa in patients at high risk of recurrent sporadic colorectal adenomas.
- change in apoptotic index after treatment as compared to placebo
- change in proliferation index and distribution of proliferating cells in crypts after treatment as compared to placebo
• change in expression of beta-catenin signaling pathway components after treatment as compared to placebo
Study design: double-blind, randomized placebo-controlled study
Study population: 68 patients, aged 50-75 years, who underwent polypectomy within 6 months before study entry, for removal of 2 or more colorectal adenomas irrespective of size and/or 1 colorectal adenoma with at least 1 of the following features: a diameter of at least 1 cm at endoscopy, a proximal localization, high-grade dysplasia or villous histology.
Intervention: Patients will be randomized to receive 3.0 g mesalazine (n=34) or placebo (n=34) once daily for 6 months in a double-blinded way. At baseline and after 6 months of treatment, a sigmoidoscopy will be performed and five biopsies of normal appearing sigmoid and rectal mucosa will be collected.
Main study parameters/endpoints: The effect of treatment with mesalazine on apoptotic and proliferation indices relative to the placebo group.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01894685
|University Medical Center Utrecht|
|Utrecht, Netherlands, 3584 CX|