Lower Lugol's Solution Concentration on Reducing the Adverse Symptoms of Chromoendoscopy With Iodine Staining

Study Overview
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Brief Summary
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This study was to test an optimal concentration of Lugol's solution which can reduce the mucosal irritation and provide high image quality to ensure endoscopy examination by a randomized blinded controlled trial.

Detailed Description
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It is widely accepted that chromoendoscopy using Lugol's solution is effective for the detection of early esophageal squamous neoplasia. However, this modality may cause severe chest pain and discomfort owing to mucosal irritation. The conventional concentration of Lugol's solution is in the range of 1.2% to 2.5% . Image quality can be guaranteed with this range of Lugol's solution. However, lead to retrosternal pain and discomfort, and can even induce erosion or ulceration in the esophagus and stomach. This study was to test whether a lower concentration of Lugol's solution, which has minimal mucosal irritation, can provide satisfied image quality by a randomized blinded controlled trial.

Official Title
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Lower Lugol's Solution Concentration on Reducing the Adverse Symptoms of Chromoendoscopy With Iodine Staining

Conditions
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Mucosal Irritation, Image Quality

Intervention / Treatment
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* Drug: 1.2% Lugol's solution
* Drug: 1.0% Lugol's solution
* Drug: 0.8% Lugol's solution
* Drug: 0.6% Lugol's solution
* Drug: 0.4% Lugol's solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients in the high-risk population of ESCC; or general risk population of ESCC between 40 to 74 years old. Definition of high-risk population of ESCC is list in supporting information33. Exclusion criteria included the following: with obvious abnormalities in stomach, confirmed by either white-light endoscopy (WLE) or pCLE, including gastric cancer, acute erosive and hemorrhagic gastritis, chronic atrophic gastritis, H. pylori infection and severe bile reflux gastritis; advanced esophageal carcinoma; known esophageal surgery or endoscopic treatment; known esophageal radiotherapy or chemotherapy; esophageal stenosis; food retention; allergy to iodine or fluorescein sodium; hyperthyroid; coagulopathy; acute bleeding; severe organ failure; pregnant or breastfeeding women.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.2% Lugol's solution<br>This group patients were given concentrations of 1.2% Lugol's solution for chromoendoscopy. | Drug: 1.2% Lugol's solution<br>* This group patients were given concentrations of 1.2% Lugol's solution for chromoendoscopy.Then biopsy specimens will be taken at the well-demarcated unstained or less-stained lesions.<br>|
| Experimental: 1.0% Lugol's solution<br>This group patients were given concentrations of 1.0% Lugol's solution for chromoendoscopy. | Drug: 1.0% Lugol's solution<br>* This group patients were given concentrations of 1.0% Lugol's solution for chromoendoscopy.Then biopsy specimens will be taken at the well-demarcated unstained or less-stained lesions.<br>|
| Experimental: 0.8% Lugol's solution<br>This group patients were given concentrations of 0.8% Lugol's solution for chromoendoscopy. | Drug: 0.8% Lugol's solution<br>* This group patients were given concentrations of 0.8% Lugol's solution for chromoendoscopy.Then biopsy specimens will be taken at the well-demarcated unstained or less-stained lesions.<br>|
| Experimental: 0.6% Lugol's solution<br>This group patients were given concentrations of 0.6% Lugol's solution for chromoendoscopy. | Drug: 0.6% Lugol's solution<br>* This group patients were given concentrations of 0.6% Lugol's solution for chromoendoscopy.Then biopsy specimens will be taken at the well-demarcated unstained or less-stained lesions.<br>|
| Experimental: 0.4% Lugol's solution<br>This group patients were given concentrations of 0.4% Lugol's solution for chromoendoscopy. | Drug: 0.4% Lugol's solution<br>* This group patients were given concentrations of 0.4% Lugol's solution for chromoendoscopy.Then biopsy specimens will be taken at the well-demarcated unstained or less-stained lesions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image Quality | Image quality is blindly quantified by a 4-point scale from the endoscopists. A higher score representing higher image quality. | intraoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric Mucosa Injury | The gastric mucosal injury caused by Lugol's solution is defined as post-staining gastritis score minus pre-staining gastritis score in pCLE. The confocal gastritis was graded 0 to 3,according to pit patterns, capillaries, and fluorescein leakage. A higher score representing more serious injury. | 1 months | 
| Adverse Events | Both a written and oral form of the Numerical Rating Scale (NRS) was provided to the patients after the endoscopy examination, used for measuring patients' retrosternal pain, retrosternal discomfort, nausea, abdominal discomfort and others. In NRS, 0 is painless, 10 is the most severe pain, less than 4 is mild pain (pain does not affect sleep), 4-6 is moderate pain, and more than 7 is severe pain (pain means unable to sleep or wake up from sleep). | 24 hours | 
| Severe Adverse Events | Severe adverse events includes allergic reactions, esophageal burns, spasms and even perforation. | 24 hours | 
| Tolerance | The 4-point scale was used to assess the tolerance of endoscopist to the esophageal spasm caused by Lugol's solution which prevent endoscopy from passing. 1-4 means the resistance as intolerable, tolerable, mild, or non-existing. | intraoperative | 
| Histology analysis | All specimens were evaluated by two experienced pathologists blind to the groups of the patients. The macroscopic and histologic diagnosis were made based on Paris classification and Vienna classification, respectively. | 3-5days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lugol's solution, esophageal squamous cell cancer, mucosal irritation, image quality