High Definition White-Light Colonoscopy vs. Chromoendoscopy for Surveillance of Lynch Syndrome.

Study Overview
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Brief Summary
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Adenomas in Lynch syndrome have an accelerated progression to colorectal cancer (CRC) which might occur despite a regular follow-up. Despite low evidence, high-definition technology (HD) and indigo-carmine chromoendoscopy (CE) are recommended for surveillance in Lynch syndrome.The investigators will conduct a prospective multicenter randomized non-inferiority study. The principal aim is to compare the adenoma detection rate with WLE vs CE. Our hypothesis is that HD-white-light endoscopy (WLE) is not inferior to CE. Therefore - under expert hands - HD-CE does not add any significant advantage over HD-WLE on adenoma detection rate in patients with Lynch syndrome.

Detailed Description
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The investigators will conduct a prospective multicenter randomized non-inferiority study. Eligible patients will be those with Lynch syndrome (known germline mutation in mismatch repair genes) who undergo surveillance colonoscopies. Patients will be sequentially assigned in a 1:1 ratio to HD-WLE or HD-CE. The method of stratified randomization based on partial colectomy history will be used to avoid proportion imbalance between groups. Participant centers must have an organized high-risk of CRC clinic and endoscopic unit provided with HD technology. Endoscopists must have a documented high adenoma detection rate and experience in performing CE in patients with high-risk conditions of CRC. The principal aim is to compare the adenoma detection rate with WLE vs CE. Principal outcome measures will be: 1) adenoma detection rate, defined as the proportion of patients with at least one adenoma in each arm; 2) number of adenomas per patient, defined as the total number of detected adenomas in each arm (HD-WLE or HD-CE) divided by the number of colonoscopies in each arm. The sample size calculation was determined for a non-inferiority study. Assuming an ADR of 28% with conventional chromoendoscopy in patients with Lynch syndrome, a 15% non-inferiority margin, a one-sided significance level of 0.05 powered at 80% and a 10% of drop-off. Based on these assumptions, it was determined that 122 patients were required for each arm (a total of 244).

Official Title
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High Definition White-Light Colonoscopy Versus Chromoendoscopy for Surveillance of Lynch Syndrome. A Prospective, Multicenter and Randomized Study

Conditions
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Lynch Syndrome

Intervention / Treatment
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* Other: High-definition white-light endoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with proven pathologic germline mutation in one of the mismatch-repair (MMR) gene (MLH1, MSH2, MSH6, PMS2 or Epcam) who will undergo surveillance colonoscopy Exclusion Criteria: Patients with total colectomy Concomitant inflammatory bowel disease Inadequate bowel preparation (Boston scale <2 in any colonic segment) Incomplete procedure (without intubation of cecum or ileo-colonic anastomosis) Previous colonoscopy in less than one year Inability to sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-definition white-light endoscopy<br>High-definition white-light endoscopy without indigo carmine instilation | Other: High-definition white-light endoscopy<br>* The intervention is do not perform chromoendoscopy<br>|
| No Intervention: High-definition chromoendoscopy<br>High-definition indigo-carmine chromoendoscopy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adenoma detection rate | Adenoma detection rate is defined as the proportion of patients with at least one adenoma in each arm | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of adenomas per patient | the total number of adenomas detected in each group (HD-WLE or HD-CE) divided by the number of colonoscopies in each group | one year | 
| Mean number per patient of total polyps |  | one year | 
| Mean number per patient of total serrated lesions |  | one year | 
| Polyp detection rate |  | one year | 
| Serrated lesions detection rate |  | one year | 
| Withdrawal time | Extubation time from the cecum to scope removal from the anus, with exception of time taken for any therapeutic intervention | 30 minutes | 
| Total procedure time | Starting with endoscope insertion and withdrawal time including therapeutic interventions | 30 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surveillance, Colorectal cancer, Colonoscopy, Adenoma, Chromoendoscopy