Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome (ChromoLynch)

May 12, 2016 updated by: Jan J Koornstra, University Medical Center Groningen

Chromoendoscopy in Lynch Syndrome Patients

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary disorder predisposing for colorectal cancer. To reduce the risk of colorectal cancer, patients undergo colonoscopy every 1-2 years. Chromoendoscopy is relatively new technique which improves the detection of adenomas, the precursor lesions of colorectal cancer. The aim of this study is to determine whether chromoendoscopy, including polypectomy of all detected lesions, reduces the development of colorectal neoplasia and the need for colectomy in LS patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomally dominantly inherited disorder that accounts for 1-2 % of colorectal cancer cases. LS is caused by germline genomic alterations in one of the mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 and hPMS2. The lifetime incidence of colorectal cancer is 20-75 % in these mutation carriers. Individuals with LS-associated colorectal cancer differ from those with sporadic disease in several ways: the tumours are diagnosed at an earlier age; the majority of tumours is located in the proximal colon; there is an increased risk of developing synchronous or metachronous colorectal cancers and the prognosis relatively favourable compared to sporadic cases. It is generally accepted that LS associated colorectal cancers develop along the adenoma-carcinoma sequence as in sporadic cases. There is evidence suggesting that the adenoma-carcinoma sequence is accelerated in LS patients as compared to the general population.

Colonoscopic screening and subsequent removal of polyps at a 3-year interval in asymptomatic at-risk members of LS families has shown to reduce the incidence of colorectal cancer and improve overall survival. However, within such an interval in surveillance programs, interval cancers have been observed. It is therefore currently recommended that MMR gene mutation carriers should be kept under surveillance by regular colonoscopy every 1-2 years beginning at the age of 20-25 or 5-10 years younger than the earliest affected family member.

LS adenomas are predominantly located in the proximal colon and frequently carry villous architecture and high-grade dysplasia, markers that are associated with an increased risk of developing colorectal cancer. Even in LS adenomas smaller than 5-7 mm in size, high-grade dysplasia can be encountered. Therefore, the identification of high-risk precursor lesions in LS is considered of paramount importance.

It is known that conventional colonoscopy has a certain miss rate for colorectal neoplasms, especially small adenomas. A few years ago, the technique of chromoendoscopy was introduced. Chromoendoscopy, in which one of various dyes are sprayed onto the colonic mucosa via a spray catheter passed through the working channel of the endoscope, offers detailed evaluation of the mucosal surface. Indigo carmine is a contrast stain that is not absorbed and does not react with the surface mucosa. In 2 large randomised controlled trials chromoendoscopy significantly increased the detection of small adenomas in the proximal colon as compared to conventional colonoscopy. Recently, 2 trials in LS patients revealed that chromoscopic endoscopy improved the detection of adenomas, particularly flat lesions, compared to conventional colonoscopy. Together, these data suggest that chromoendoscopy may improve detection rates of significant neoplastic colonic lesions in LS patients. However, the true value of chromoendoscopy in the management of LS patients remains to be demonstrated.

The aim of this study is to determine whether chromoendoscopy, including polypectomy of all detected lesions, reduces the development of colorectal neoplasia and the need for colectomy in LS patients at follow-up endoscopy.

The results of the study will indicate the value of chromoendoscopy in the management of LS patients and whether the technique should be implemented in current surveillance procedures.

Study Type

Interventional

Enrollment (Actual)

240

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Groningen, Netherlands
        • University Medical Center Groningen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • proven carrier of a MLH1, MSH2 or MSH6 mutation
  • age between 20 and 70 years
  • written informed consent

Exclusion Criteria:

  • previous large bowel surgery
  • psychological/physical conditions hampering compliance with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: 1
Conventional colonoscopy
Experimental: 2
Colonoscopy using chromoendoscopy
Procedure: Chromoendoscopy
Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoints of the study are the number of adenomas, advanced adenomas, carcinomas at baseline and the number of the number of adenomas, advanced adenomas, carcinomas and the number of patients requiring colectomy at 2-year follow-up.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
The secondary endpoints of the study are the number of complications from colonoscopy at baseline and at 2-year follow-up.
Time Frame: baseline and 2 years
baseline and 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Collaborators

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
The Netherlands Cancer Institute
Leiden University Medical Center
University Medical Center Nijmegen
Free University Medical Center

Investigators

  • Principal Investigator: Jan J Koornstra, MD PhD, University Medical Center Groningen, Netherlands
  • Study Director: Jan H Kleibeuker, MD PhD, University Medical Center Groningen, Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

May 18, 2009

First Submitted That Met QC Criteria

May 18, 2009

First Posted (Estimate)

May 20, 2009

Study Record Updates

Last Update Posted (Estimate)

May 13, 2016

Last Update Submitted That Met QC Criteria

May 12, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChromoLynch

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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