Prospective, open-label, single-arm, early feasibility study (EFS) in 2 Patient cohorts: Cohort A - Dose finding / Dose response study in patients with various etiologies undergoing Esophagectomy and Cohort B - Patients with Barrett's Esophagus (BE) with Low-Grade Dysplasia (LDG) or High-Grade Dysplasia (HGD) without a visible (excisable) lesion. This is a pilot study which plan to enroll up to 5 eligible patients in the First Cohort (A) and up to 15 patients in the Second Cohort (B) of the study.
Study intervention means tha application of different doses of laser energy in the ablation of esophageal mucosa using the Digma System and the Endoscopic Gastrointestinal Ablation Device (EGAD) procedure (Cohort A) followed by application of the optimal dose for treatment of patients with BE with Low-Grade Dysplasia (LGD) or High-Grade Dysplasia (HDG) without a visible lesion (Cohort B). EGAD is a proprietary, controlled laser ablation system for the treatment of endoluminal pathologies of the gastrointestinal tract. EGAD achieves high precision through a unique optical design that controls laser energy, beam size, wavelength, and focal plane. This allows for effective ablation that is limited to the mucosa of pre-selected regions of interest, avoiding a wider and deeper injury to healthy tissue. EGAD procedure can be performed safely in a standard endoscopy suite under direct endoscopic visualization. In this First-in-Human pilot feasibility study, we plan to assess the feasibility of EGAD for achieving mucosal ablation (1) in healthy esophageal tissue in patients undergoing esophagectomy for esophageal cancer or other indications (Barrett's mucosa may be ablated as well) - Cohort A; and (2) In patients with Barrett's Esophagus with low and/or high-grade dysplasia (BORN = Barrett´s Oesophagus-Related Neoplasia) without a visible (excisable) lesion - Cohort B.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Application of different doses of laser energy in the ablation of esophageal mucosa using the Digma System and the EGAD procedure (Cohort A) followed by application of the optimal dose for treatment of patients with BE with LGD or HDG without a visible lesion (Cohort B).
Fakultní nemocnice u sv. Anny v Brně, Gastroenterologické a hepatologické oddělení
Brno, Czechia
RECRUITINGCohort A: Incidence of severe immediate adverse events (AEs)
Cohort A: Incidence of severe immediate adverse events (AEs) that are directly associated with EGAD procedure (esophageal perforation, bleeding, patient hemodynamic or respiratory decompensation during the procedure or death following the procedure).
Time frame: Day 1, ESOPHAGECTOMY surgery
Cohort B: Incidence of immediate severe AE
Cohort B: Incidence of immediate severe AE (including esophageal perforation, bleeding, patient hemodynamic or respiratory decompensation during the procedure or death following the procedure, esophageal stricture rate after ablation).
Time frame: Day 1
Cohort B: Incidence of late severe AE
Cohort B: Incidence of late severe AE (including esophageal perforation, bleeding, patient hemodynamic or respiratory decompensation during the procedure or death following the procedure, esophageal stricture rate after ablation). A dedicated designed Questioner will be used.
Time frame: 10-12 months follow-up, following each visit and procedure
Cohort A: Dose response effects of ablation on mucosal tissue
Cohort A: Dose response effects of ablation on mucosal tissue (assessed by histopathological assessment of mucosal eradication (coagulation necrosis).
Time frame: Day 1, ESOPHAGECTOMY surgery
Cohort B: Eradication of dysplasia level and of visible segment of BE
Cohort B: Eradication of dysplasia level and of visible segment of BE assessed macroscopically.
Time frame: 10-12 months follow-up, at each follow-up visit
Adverse events related to the procedure (Cohort A+B)
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Incidence of any adverse events related to the procedure.
Time frame: Day 1
Maximal ablation depth (cohort A)
Evaluation of maximum ablation depth. Grading of histology to be conducted in accordance with accepted histological score grading such as depicted in van Munster SM et al. Endoscopy 2021,53,1162-1168 wherein thermal injury was semi-quantitatively scored and the proportion of tissue injury was calculated (depth of thermal changes / total tissue thickness).
Time frame: Day 1, ESOPHAGECTOMY surgery
Maximal ablation volume (cohort A)
Evaluation of maximum ablation volume. Following esophagectomy, all resected ablated tissue will be submitted for histopathologic analysis. Analysis of the EGAD treatment ablation sites for evaluation of the ablation outcomes (such as extent of mucosal ablation and depth of penetration) will be conducted per a predefined histological protocol and criterium.
Time frame: Day 1, ESOPHAGECTOMY surgery
Dose response effect of treatment(s) on depth-of-penetration. (cohort A)
Evaluation of the dose-dependent effect of treatment on penetration depth, examining how different intensities or doses of the therapy used affect the extent to which the treatment penetrates the tissue, in order to assess the relationship between dose, efficacy, and the potential risks of excessive treatment. Grading of histology to be conducted in accordance with accepted histological score grading such as depicted in van Munster SM et al. Endoscopy 2021,53,1162-1168 wherein thermal injury was semi-quantitatively scored and the proportion of tissue injury was calculated (depth of thermal changes / total tissue thickness).
Time frame: Day 1, ESOPHAGECTOMY surgery
Assessment of collateral impact as assessed by histopathologic evaluation.
Assessment of secondary effects, in which histopathological examination is used to assess the extent of undesirable changes in tissues outside the target area in order to determine whether the procedure has caused damage to surrounding structures or other unforeseen tissue reactions.
Time frame: 10-12 months follow-up or when eradication of BE is achieved
Rate of complete eradication of dysplasia (cohort B)
The degree of complete eradication of dysplasia, which assesses the extent to which all dysplastic changes in the mucosa have been completely removed or replaced by normal epithelium after treatment, in order to evaluate the overall effectiveness of the therapy and minimize the risk of persistent or recurrent precancerous lesions.
Time frame: 10-12 months follow-up
Rate of eradication of intestinal metaplasia. (cohort B)
The degree of eradication of intestinal metaplasia, which monitors how much of the pathologically altered mucosa has been successfully removed or replaced by normal epithelium after treatment in order to assess the effectiveness of therapy and the likelihood of long-term remission.
Time frame: 10-12 months follow-up
Eradication of macroscopically visible segment of BE.
Eradication of macroscopically visible Barrett's esophagus, in which complete removal of all clearly altered mucosal areas is assessed to ensure that the pathological epithelium has been treated in its entirety and that no residual focal changes remain.
Time frame: 10-12 months follow-up
Assessments of lesion ablation - safe margin area.
Evaluation of lesion ablation, focusing primarily on the size and consistency of the safety margin to ensure that the treated area sufficiently exceeds the boundaries of the lesion and minimizes the risk of incomplete removal.
Time frame: 10-12 months follow-up
Assessment of technical aspects of the procedure-time
Evaluation of the technical time of the procedure (minutes or hours), assessing in particular the time required.
Time frame: Day 1