Clinical trial NCT02575287: Minimal Injuries From Esophagus Detected by Optical Enhancement System™ Associated to Optical Magnification HD Scopes
Official title: Mucosal and Minimal Injuries Detected Through Digital Chromoendoscopy Using Optical Enhancement System™ Associated to High Definition Plus Optical Magnification in Non Erosive Gastroesophageal Reflux Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non Erosive Reflux Disease
GERD
Lead sponsor: Instituto Ecuatoriano de Enfermedades Digestivas
Sponsor class: OTHER
First posted: 2015-10-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients that had reflux symptoms (heartburn and regurgitation) and 8 or more points at the Spanish version of GERD questionnaire validated by Zavala-González et al. underwent an upper videoendoscopy using initially high definition white light and then digital chromoendoscopy (I-Scan™) in the three different image algorithms. If the esophagus was normal and no changes were seen by these two techniques, they were considered as NERD patients and a pH-impedanciometry was performed as gold standard study, in order to diagnosis reflux disease. We considered a GERD diagnosis with more than 73 episodes of reflux in 24 hours or acid exposure time abnormal with ph\<4 measured in more than 4,2%of the time over 24 hours.

Brief summary: White light endoscopy remains the gold standard technique to evaluate gastrointestinal tract. Gastroesophageal Reflux Disease (GERD) is defined as presence of reflux symptoms (heartburn and regurgitation) associated or not with lesions in esophageal mucosa. Based on findings at videoendoscopy GERD patients can have a complicated reflux disease (erosive esophagitis) or not and be considered as a non erosive reflux disease (NERD). 60% of GERD patients have normal endoscopy (NERD) and requires further studies to achieve a definitive diagnosis. Based on this fact is that the study will be focus on NERD patients.

Recently an image-enhanced endoscopic technology using a pre-processor band-limited light called Optical Enhancement system (OE system™), was developed (Pentax Medical). This new technology combines digital signal processing with optical filters that limit the spectral characteristics of the illumination light. The new innovated optical filters achieve higher overall transmittance by connecting the peaks of the hemoglobin absorption spectrum (415 nm, 540 nm and 570 nm) creating a continuous wavelength spectrum. There are two modes with different OE filters (Mode 1 and Mode 2). Mode 1 is designed to improve visualization of microvessels with a sufficient amount of light, and Mode 2 is designed to improve contrast of white-light observation by bringing the color tone of the overall image closer to that of natural color.

In addition, new scopes has been developed which combines high definition images with optical magnification called Magniview™. These scopes increase the image up to 136 times with a better quality of image than standard scopes without optical zoom. Sharma et al. evaluated esophageal changes in NERD patients using a similar pre-processor filter called Narrow Band Imaging (NBI). They found that a significantly higher proportion of patients with NERD had an increased number, dilation and tortuosity of the microscopic intrapapillary capillary loops (IPCLs), and were considered the best predictors for diagnosing NERD. They used optical chromoendoscopy technology (NBI) associated to magnification scopes (Olympus GIF Q240Z, 115x), but they did not evaluated if the contribution with this technology to the observations found in GERD patients were as a result of the NBI or the magnification scopes. The investigators opinion is that chromoendoscopy is useful but is the magnification what makes up the difference.

Detailed description: Sharma et al. described in detail the changes of the intrapapillary capillaries seen with reflux inflammation. In the normal esophageal mucosa, submucosa all vessels are connected to the arborescent vascular network. Intrapapillary capillaries arise from the fourth branch of the arborescent vessels into the epithelial papillae and form single loops called IPCLs. It has been shown that IPCLs dilate and elongate along with an increase in the number and density of arborescent vessels in mucosal cancer. These changes are similar to those observed in inflammation.

Estimated enrollment: 100 patients (NERD group: 50 patients and control group: 50 patients)

Study design: This is an observational and analytical cross-section, population - based survey study, with prospective case collection, non-randomized and simple blind, performed in a Tertiary Academic Center.

Study Design

* Allocation: Non randomized, simple blind
* Endpoint Classification: Efficacy
* Intervention Model: Non interventional
* Primary Purpose: Diagnosis

Setting: Instituto Ecuatoriano de Enfermedades Digestivas (IECED), OmniHospital Academic Tertiary Center. We will include patients from September 2015 to November 2015. Patients will be recruited from the gastroenterology unit (IECED). The study protocol and consent form has been approved by the IRB and will be conducted according to the declaration of Helsinki. Patients will sign an informed consent and answer a questionnaire that includes constitutional data (sex, age, weight (Kg), height (m), BMI (Kg/m2), chronic diseases, medication and main reflux symptom).

Population selection, inclusion and exclusion criteria: Patient selection was done after the following analysis. Each patients that had reflux symptoms (heartburn and regurgitation) and 8 or more points at the Spanish version of GERD questionnaire validated by Zavala-González et al., underwent an upper videoendoscopy using initially high definition white light and then virtual chromoendoscopy (I-Scan™) in the three different image algorithms. After performing an upper endoscopy completely and reach the line Z, the entire esophagus was evaluated (upper, middle and lower esophagus). If they had any signs of reflux as ulcerative esophagitis, esophageal strictures, Barrett's esophagus or any erosive sign according to Los Angeles classification (Grade A to D), they were classified as GERD patients and were excluded from the protocol. The endoscopies were performed by the same three endoscopist that will carry on the study.

If the esophagus was normal and no changes were seen by these two techniques, they were considered as NERD patients and a pH-impedanciometry was performed as gold standard study, in order to diagnosis reflux disease. GERD diagnosis was considered when there were more than 73 episodes of reflux episodes in 24 hours or acid exposure time (AET) abnormal with ph \<4 measured in more than 4,2%of the time over 24 hours.

After this phase, the investigators could discriminate patients that had a normal pH-impedanciometry and no reflux disease from the real NERD patients with reflux disease proven by a positive pH-impedanciometry with symptoms and no lesion.

Two groups were selected. One was the control group and included patients that agreed to be part of the study and for whom we have certainty that they have no GERD (reflux symptoms but negative upper endoscopy with high definition white light or I-Scan and negative Ph-impedanciometry). The other group includes NERD patients with reflux symptoms, a positive Ph-Impedanciometry but a negative upper endoscopy with high definition white light or I-Scan.

Survey: It will be use the Spanish version of the Gastroesophageal Reflux Disease Questionnaire survey, validated in Mexico by Zavala-González et al., but in an Ecuadorian population.

1. How often did you have a burning feeling behind your breastbone (heartburn)?
2. How often did you have stomach contents (liquid or food) moving upwards to your throat or mouth (regurgitation)?
3. How often did you have pain in the center of the upper stomach?
4. How often did you have nausea?
5. How often did you have difficulty getting a good night's sleep because of your heartburn and/or regurgitation?
6. How often did you take additional medication for your heartburn and/or regurgitation, other than what the physician told you to take (such as Tums, Rolaids and Maalox)?

Endoscopic technique: All the patients included in the protocol (NERD group and control group) will be studied by upper endoscopy with Magniview™ scopes and EPK-i7010 processor (OE system™).

The technique involves the use of a distal rubber hood (OE-A58) at the tip of the scope (EG-2990Zi). After reaching the line Z, the four quadrants of the three levels of the esophagus (upper, middle and lower esophagus) will be evaluated in the same way. The cup will contact to the esophageal mucosa and water will be instilled. Initially only the OE system™ will be used (mode 1) If there is no evidence of minimal changes, the optical magnification will be implemented through the actions of a button on the Magniview scope. Finally the OE system™ will be off and only the Magniview™ will be used with white light.

All changes seen will be recorded (by video and pictures) in the specific phase of the study (OE system™ alone, OE system™ with Magniview™ or Magniview™ alone). Finally, biopsies will be taken in both groups (one of each esophagus level randomly and one targeted biopsy to any lesion). The endoscopies will be performed by three endoscopist blind to the group selection and trained on this new technology (all of them with more than 10 procedures).

Mucosal minimal changes will be evaluated as the Sharma et al. classification:

1. IPCLs (number, dilatation, and tortuosity). Dilatation of IPCLs will be recognized as a change in the pattern characterized by increased size or caliber of individual IPCLs. Tortuosity is define by the presence of corkscrewing or the twisted nature of individual IPCLs.
2. Presence of microerosions (definitive mucosal breaks not visible at standard endoscopy).
3. Vascularity at the squamocolumnar junction.
4. Presence of columnar island in the distal esophagus.
5. Ridge-villous pattern below the squamocolumnar junction characterized by the presence of uniform, longitudinally aligned ridges alternating with a villiform pattern.

Interobserver and Intraobserver Agreement: A data set containing pictures of the three esophagus levels in the three phase of the study (OE system™ alone, OE system™ with Magniview™ or Magniview™ alone) will be presented to three blinded endoscopists, who will confirm or not the findings. Inter- and intraobserver reproducibility will be measured based on comparison of still images between the three investigators. To evaluate the intraobserver agreement each investigator will assess the images three times and the answers will be compared. To evaluate the interobserver agreement all answers between the three investigators will be compared.

Statistical analysis: Baseline characteristics as age, gender, body mass index, symptoms will be compared between case and control group using Chi-square o Fisher Test for categorical variable, and for continuing variables, we will use the Mann-Whitney Test. Diagnosis efficacy will be measured thought sensitive, specificity and accuracy. All the statistical analysis will be performed using SPSS software suite v.22.

Limitations

* Only patients with typical reflux symptoms will participate in the study (heartburn or regurgitation).
* The protocol will be performed in only one center.

Eligibility criteria: Inclusion Criteria:

* Above 18 years old patients
* Who agree to participate in the study
* Patients with reflux symptoms (heartburn and regurgitation), with8 or more points at the GERD questionnaire and no evidence of ulcerative esophagitis, esophageal strictures, Barrett's esophagus or any erosive sign according to Los Angeles classification (Grade A to D) in the upper endoscopy using white light nor I-Scan™

Exclusion Criteria:

* Patients with ulcerative esophagitis, esophageal strictures, Barrett's esophagus or any erosive sign according to Los Angeles classification (Grade A to D)
* Patients with medical history of any kind of esophagitis (including actinic, caustic or eosinophilic), achalasia.
* Esophageal varices
* Patients with evidence of cancer or mass lesion in the esophagus
* Protons bump inhibitor consumption for at least 3 weeks before endoscopy
* Inability to discontinue non steroidal anti-inflammatory drugs or aspirin prior to the study
* Severe uncontrolled coagulopathy
* Gastric lesions (ulcer, polyp, cancer), severe gastroparesis
* Prior history of esophageal or gastric surgery.
* Pregnancy and lactation

Primary outcomes:
measure: Digital chromoendoscopy and optical magnification in the diagnosis of intrapapillary loops (IPCLs) in esophagus. Number of participants with increased number of IPCLs, dilatation or tortuosity of IPCLs
timeFrame: two months
Secondary outcomes:
measure: Number of patients in whom the minimal esophageal changes are diagnosed by the digital chromoendoscopy without using the magnification, or with the magnification without using the digital chromoendoscopy or using both.
timeFrame: two months
measure: Number of patients with increased number, dilatation or tortuosity of the intrapapilary loops on endoscopic image and have a positive biopsy for inflammation of mucosa.
timeFrame: two months
Other outcomes:
Locations:
city: Guayaquil
country: Ecuador
facility: Ecuadorian Institute of Digestive Diseases, Omnihospital
state: Guayas
Study officials:
affiliation: Ecuadorian Institute of Digestive Diseases
name: Carlos A Robles-Medranda, MD
role: PRINCIPAL_INVESTIGATOR
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