Lynch SyndromeChromoLynchNCT00905710
Chromoendoscopy to Decrease the Risk of Colorectal Neoplasia in Lynch Syndrome
A study testing Chromoendoscopy in people with Lynch Syndrome, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- Lynch Syndrome
- What is being tested?
- Chromoendoscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2008to May 2016
- Phase
- Interventional
- 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 20 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- proven carrier of a MLH1, MSH2 or MSH6 mutation
- age between 20 and 70 years
- written informed consent
Who cannot join
- previous large bowel surgery
- psychological/physical conditions hampering compliance with the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Lynch Syndrome
- Being tested
- Chromoendoscopy
- Keywords
- colorectal adenomas, colorectal cancer, Lynch syndrome, chromoendoscopy
- Medical subject headings
- Colorectal Neoplasms, Hereditary Nonpolyposis, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChromoendoscopyProcedure or surgery
Chromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Conventional colonoscopy |
| 2 | Experimental | Colonoscopy using chromoendoscopy Receives: Procedure: Chromoendoscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (1)
The secondary endpoints of the study are the number of complications from colonoscopy at baseline and at 2-year follow-up.
Measured: baseline and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2009 (estimated)
- Study startSep 2008
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lynch SyndromeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 240 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center, Universitair Ziekenhuis Brussel, University Medical Center Nijmegen, The Netherlands Cancer Institute, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Responsible party
- Principal investigator, Jan J Koornstra, University Medical Center Groningen
- Investigators
- Jan J Koornstra, MD PhD, Principal investigator, University Medical Center Groningen, netherlandsJan H Kleibeuker, MD PhD, Study director, University Medical Center Groningen, Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00905710
- Sponsor's protocol ID
- ChromoLynch
- Acronym
- ChromoLynch
- Status last verified
- May 2016
- First submitted
- 18 May 2009
- Last updated
- 13 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stoffel EM, Turgeon DK, Stockwell DH, Normolle DP, Tuck MK, Marcon NE, Baron JA, Bresalier RS, Arber N, Ruffin MT, Syngal S, Brenner DE; Great Lakes New England Clinical Epidemiology and Validation Center of the Early Detection Research Network. Chromoendoscopy detects more adenomas than colonoscopy using intensive inspection without dye spraying. Cancer Prev Res (Phila). 2008 Dec;1(7):507-13. doi: 10.1158/1940-6207.CAPR-08-0096.
PubMed 19139000Huneburg R, Lammert F, Rabe C, Rahner N, Kahl P, Buttner R, Propping P, Sauerbruch T, Lamberti C. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening. Endoscopy. 2009 Apr;41(4):316-22. doi: 10.1055/s-0028-1119628. Epub 2009 Apr 1.
PubMed 19340735Haanstra JF, Dekker E, Cats A, Nagengast FM, Hardwick JC, Vanhoutvin SA, de Vos Tot Nederveen Cappel WH, Vasen HF, Kleibeuker JH, Koornstra JJ. Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial. Gastrointest Endosc. 2019 Oct;90(4):624-632. doi: 10.1016/j.gie.2019.04.227. Epub 2019 Apr 24.
PubMed 31028782
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chromoendoscopy in Lynch Syndrome Patients
- ClinicalTrials.gov ID
- NCT00905710
- Acronym / sponsor ID
- ChromoLynch / ChromoLynch
- Conditions
- Lynch Syndrome
- Keywords
- colorectal adenomas, colorectal cancer, Lynch syndrome, chromoendoscopy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 240 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Leiden University Medical Center, Universitair Ziekenhuis Brussel, University Medical Center Nijmegen, The Netherlands Cancer Institute, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- Sep 2008
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 20 May 2009 (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.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | No intervention | –Conventional colonoscopy |
| 2 | Experimental | Procedure: ChromoendoscopyColonoscopy using chromoendoscopy |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- proven carrier of a MLH1, MSH2 or MSH6 mutation
- age between 20 and 70 years
- written informed consent
Key exclusion criteria (2 listed)
- previous large bowel surgery
- psychological/physical conditions hampering compliance with the study protocol
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 |
|---|---|---|
| ChromoendoscopyChromoendoscopy: spraying of the mucosa of the right colon with indigo-carmine | Procedure or surgery | 2 |
Primary outcome
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
1 secondary outcome
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
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 13 May 2016.
- Background: PubMed 19139000Stoffel EM, Turgeon DK, Stockwell DH, Normolle DP, Tuck MK, Marcon NE, Baron JA, Bresalier RS, Arber N, Ruffin MT, Syngal S, Brenner DE; Great Lakes New England Clinical Epidemiology and Validation Center of the Early Detection Research Network. Chromoendoscopy detects more adenomas than colonoscopy using intensive inspection without dye spraying. Cancer Prev Res (Phila). 2008 Dec;1(7):507-13. doi: 10.1158/1940-6207.CAPR-08-0096.
- Background: PubMed 19340735Huneburg R, Lammert F, Rabe C, Rahner N, Kahl P, Buttner R, Propping P, Sauerbruch T, Lamberti C. Chromocolonoscopy detects more adenomas than white light colonoscopy or narrow band imaging colonoscopy in hereditary nonpolyposis colorectal cancer screening. Endoscopy. 2009 Apr;41(4):316-22. doi: 10.1055/s-0028-1119628. Epub 2009 Apr 1.
- Derived from this study: PubMed 31028782Haanstra JF, Dekker E, Cats A, Nagengast FM, Hardwick JC, Vanhoutvin SA, de Vos Tot Nederveen Cappel WH, Vasen HF, Kleibeuker JH, Koornstra JJ. Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial. Gastrointest Endosc. 2019 Oct;90(4):624-632. doi: 10.1016/j.gie.2019.04.227. Epub 2019 Apr 24.
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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.
Jan J Koornstra, MD PhD principal investigator
University Medical Center Groningen, netherlands
Jan H Kleibeuker, MD PhD study director
University Medical Center Groningen, Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Chromoendoscopy in people with Lynch Syndrome, run by University Medical Center Groningen 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 3 inclusion and 2 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 13 May 2016. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00905710, which also lists 3 linked publications.
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 13 May 2016.