Mesalazine Effects in Sporadic Colorectal Adenoma Patients
Condition: Sporadic Colorectal Adenoma
MeSH terms: Adenoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Several studies indicate that mesalazine might have a preventive effect on recurrence of
      adenomas in patients with and without inflammatory bowel disease. As mesalazine has limited
      adverse effects, it is an attractive candidate for chemoprevention. In this study we aim to
      investigate the antineoplastic properties of mesalazine in patients with sporadic colorectal
      adenomas.
    

Detailed description: 
      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.

      Primary endpoints:

        -  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

      Secondary endpoint:

      • 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.
    

Intervention name(s): Mesalazine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Mesalazine 3 grams, once daily for six months; Placebo 3 grams, once daily for six months
Intervention MeSH terms: Mesalamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Colorectal; Adenoma; Recurrence; Mesalazine; Chemoprevention