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

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Leiden University Medical Center
Free University Medical Center
University Medical Center Nijmegen
The Netherlands Cancer Institute
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Information provided by:
University Medical Centre Groningen
ClinicalTrials.gov Identifier:
NCT00905710
First received: May 18, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  Purpose

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.


Condition Intervention
Lynch Syndrome
Procedure: Chromoendoscopy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Chromoendoscopy in Lynch Syndrome Patients

Resource links provided by NLM:


Further study details as provided by University Medical Centre Groningen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: September 2008
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
Conventional colonoscopy
Experimental: 2
Colonoscopy using chromoendoscopy
Procedure: Chromoendoscopy
Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine

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.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00905710

Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands
Sponsors and Collaborators
University Medical Centre Groningen
Leiden University Medical Center
Free University Medical Center
University Medical Center Nijmegen
The Netherlands Cancer Institute
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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
  More Information

Publications:
Responsible Party: Dr Jan J Koornstra, University Medical Centre Groningen
ClinicalTrials.gov Identifier: NCT00905710     History of Changes
Other Study ID Numbers: ChromoLynch
Study First Received: May 18, 2009
Last Updated: May 18, 2009
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by University Medical Centre Groningen:
colorectal adenomas
colorectal cancer
Lynch syndrome
chromoendoscopy

Additional relevant MeSH terms:
Colorectal Neoplasms, Hereditary Nonpolyposis
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on April 17, 2014