Sporadic Colorectal AdenomaPhase 2NCT01894685
Mesalazine Effects in Sporadic Colorectal Adenoma Patients
A Phase 2 study testing Mesalazine in people with Sporadic Colorectal Adenoma, run by UMC Utrecht at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Sporadic Colorectal Adenoma
- What is being tested?
- Mesalazine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteNetherlands
- Study dates
- Jul 2012to Jun 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Medical Center Utrecht
Utrecht, Utrecht, 3584 CX
About this study
Official title: Chemopreventive Effects of Mesalazine in Patients at High Risk of Recurrent (Nonfamilial) Colorectal Adenomas
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.
Read the 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.
- Conditions
- Sporadic Colorectal Adenoma
- Being tested
- Mesalazine, Placebo
- Keywords
- Colorectal, Adenoma, Recurrence, Mesalazine, Chemoprevention
- Medical subject headings
- Adenoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MesalazineDrug
Mesalazine 3 grams, once daily for six months
PlaceboDrug
Placebo 3 grams, once daily for six months
| Study group | Role | What they receive |
|---|---|---|
| Mesalazine | Experimental | Mesalazine, 3 grams once daily for six months Receives: Drug: Mesalazine |
| Placebo | Placebo comparator | Placebo, 3 grams, once daily for six months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apoptotic index
Change in apoptotic index after treatment with mesalazine as compared to placebo
Measured: 6 months
Proliferation index
Change in proliferation index and distribution of proliferating cells in crypts after treatment with mesalazine as compared to placebo
Measured: 6 months
Secondary outcomes (1)
Expression of β-catenin signaling pathway
Change in expression of β-catenin signaling pathway components after treatment with mesalazine as compared to placebo
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startJul 2012
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sporadic Colorectal AdenomaStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. dr. P.D. Siersema, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01894685
- Sponsor's protocol ID
- NL36557.041.11
- Status last verified
- Dec 2015
- First submitted
- 3 Jul 2013
- Last updated
- 8 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemopreventive Effects of Mesalazine in Patients at High Risk of Recurrent (Nonfamilial) Colorectal Adenomas
- ClinicalTrials.gov ID
- NCT01894685
- Acronym / sponsor ID
- NL36557.041.11
- Conditions
- Sporadic Colorectal Adenoma
- Keywords
- Colorectal, Adenoma, Recurrence, Mesalazine, Chemoprevention
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesalazine | Experimental | Drug: MesalazineMesalazine, 3 grams once daily for six months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, 3 grams, once daily for six months |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- inflammatory bowel disease
- familial colorectal cancer syndrome
- history of colorectal carcinoma
- history of surgery to the large bowel (except appendectomy)
- chronic renal insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MesalazineMesalazine 3 grams, once daily for six months | Drug | Mesalazine |
| PlaceboPlacebo 3 grams, once daily for six months | Drug | Placebo |
Primary outcome
Apoptotic index
Time frame: 6 months
Change in apoptotic index after treatment with mesalazine as compared to placebo
Proliferation index
Time frame: 6 months
Change in proliferation index and distribution of proliferating cells in crypts after treatment with mesalazine as compared to placebo
1 secondary outcome
Expression of β-catenin signaling pathway
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesalazine in people with Sporadic Colorectal Adenoma, run by UMC Utrecht at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Apoptotic index (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2015.