Mesalazine Effects in Sporadic Colorectal Adenoma Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by UMC Utrecht
Sponsor:
Information provided by (Responsible Party):
Prof. dr. P.D. Siersema, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01894685
First received: July 3, 2013
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Sporadic Colorectal Adenoma
Drug: Mesalazine
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 68
Study Start Date: July 2012
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesalazine
Mesalazine, 3 grams once daily for six months
Drug: Mesalazine
Mesalazine 3 grams, once daily for six months
Placebo Comparator: Placebo
Placebo, 3 grams, once daily for six months
Drug: Placebo
Placebo 3 grams, once daily for six months

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.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age: 50-75 years
  • having undergone complete colonoscopy with polypectomy for removal of
  • 2 or more colorectal adenomas, irrespective of size, and/or
  • 1 colorectal adenoma:
  • of at least 1 cm in diameter and/or
  • located proximal to the splenic flexure and/or
  • with high-grade dysplasia and/or villous histology

Exclusion Criteria:

  • inflammatory bowel disease
  • familial colorectal cancer syndrome
  • history of colorectal carcinoma
  • history of surgery to the large bowel (except appendectomy)
  • chronic renal insufficiency
  • chronic hepatic insufficiency
  • allergy to salicylates
  • diabetes mellitus (higher risk for developing renal disease)
  • coagulation disorder or anticoagulant use, which cannot be temporarily discontinued (precludes biopsy taking)
  • asthma
  • prescription use of acetylsalicylic acid or calcium carbasalate (high- and low-dose) or other NSAIDs
  • use of medicines which may interact with mesalazine: methotrexate, thiopurines, cyclosporine, coumarin anticoagulants and rifampicin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01894685

Contacts
Contact: P D Siersema, MD, PhD +31-88-7559338 p.d.siersema@umcutrecht.nl

Locations
Netherlands
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
UMC Utrecht
  More Information

No publications provided

Responsible Party: Prof. dr. P.D. Siersema, Prof. dr. (MD, PhD) P.D. Siersema, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01894685     History of Changes
Other Study ID Numbers: NL36557.041.11
Study First Received: July 3, 2013
Last Updated: May 19, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
Colorectal
Adenoma
Recurrence
Mesalazine
Chemoprevention

Additional relevant MeSH terms:
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Mesalamine
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 22, 2014