Transpyloric Stenting as a Predictor for G-POEM for Refractory Gastroparesis

Study Overview
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Brief Summary
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This is a prospective sham study to investigate the role of transpyloric stenting with lumen apposing metal stent (LAMS) as a predictor for clinical response to gastric per-oral endoscopic pyloromyotomy (GPOEM) for refractory gastroparesis. The study hypothesizes that clinical improvement with transpyloric stenting in patients with refractory gastroparesis is a predictor of subsequent clinical success of GPOEM.

Detailed Description
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Gastroparesis is defined as a complex syndrome of symptoms including early satiety, post-prandial fullness, nausea, vomiting, bloating, and upper abdominal pain with a corresponding objective delay in gastric emptying in the absence of mechanical obstruction. Recent epidemiologic data has shown a substantial increase of 158% in hospitalizations related to gastroparesis in recent years. The pathogenesis underlying gastroparesis is complex with multiple potential underlying mechanisms including impaired gastric accommodation, autonomic neuropathy, vagal nerve injury, uncoordinated gastric contractility, and pyloric dysfunction. Effective and durable medical treatment of gastroparesis has remained clinically challenging. Currently metoclopramide is the only medication approved by the U.S. Food and Drug Administration (FDA) for diabetic gastroparesis, and treatment courses are recommended to be limited to a maximum of 12 weeks due to the risk of the irreversible side effect of tardive dyskinesia. Surgical treatments for gastroparesis also remain limited, with sparse existing data to support the use of implanted gastric electrical stimulation for treatment of refractory gastroparesis, which is currently approved by the FDA only for compassionate use. More recently, surgical pyloroplasty has been examined in treatment of gastroparesis, which has long been recognized as a technique to improve gastric drainage for mechanical obstructions and during elective vagotomy after gastric surgery. A recent study examined surgical pyloroplasty in 28 patients with post-surgical gastroparesis with 83% patients reporting significant clinical improvement at one-month follow-up but current surgical literature remains limited in this area and has focused primarily on post-surgical gastroparesis. Given the lack of effective treatment options, endoscopic therapies for gastroparesis have recently been investigated as adjunctive or alternative methods to treat gastroparesis. Pyloric dysfunction characterized by pyloric restriction or pylorospasm with prolonged periods of increased pyloric tone and contractions has been brought to attention as an area of targetable therapy for a subset of patients with gastroparesis. Pyloric botulinum toxin injections initially demonstrated improvement in gastric emptying after treatment, but subsequent results from double-blinded placebo-control studies failed to demonstrate a difference in symptoms compared to placebo. Transpyloric stenting was initially reported in 2013 in three cases of refractory gastroparesis with placement of a double layered, fully-covered, Niti-S self-expandable metal stent (TaeWoong Medical) across the pylorus with improvement in gastric emptying and symptoms in all three patients. A subsequent study of 30 patients with refractory gastroparesis who underwent transpyloric stenting demonstrated high technical success of stent placement (98%) with improvement of clinical symptoms in 75% of patients and 4-hour gastric emptying studies in 69% of patients. Stent migration was found to occur in 59% of patients without any associated adverse events. Current focus on transpyloric stenting in gastroparesis centers around determining optimal stent type and method of stent anchorage as well as the role of transpyloric stenting in treatment given lack of long-term durability. With advancements in endoscopic submucosal dissection, G-POEM has recently come in to light as a minimally invasive technique to treat refractory gastroparesis. Esophageal endoscopic myotomy has previously been well-described as a procedure for treatment of achalasia, and this technique was adopted by in 2013 with the first G-POEM for refractory gastroparesis. A subsequent multicenter study in 2017 reported on 30 patients with refractory gastroparesis who underwent G-POEM with a technical success rate of 100%. At 5.5-month follow-up, 86% of patients were found to have clinical response. Repeat gastric emptying studies after G-POEM also normalized or improved in 47% and 37% of patients respectively. G-POEM has now gained both national and international recognition in succeeding studies as a feasible and safe technique to effectively treat refractory gastroparesis in a subset of patients. Identifying predictors of success of G-POEM for treatment of gastroparesis is essential in further recognizing appropriate patients who would benefit from this therapy. As transpyloric stenting and G-POEM share underlying mechanisms of disruption of the pylorus, the investigators propose that improvement with transpyloric stenting in patients with refractory gastroparesis can be a predictor of subsequent response with G-POEM.

Official Title
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Transpyloric Stenting for Refractory Gastroparesis Prior to Gastric Per-Oral Endoscopic Myotomy: A Prospective Sham Study

Conditions
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Gastroparesis

Intervention / Treatment
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* Device: Transpyloric stent
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients greater than 18 years of age with gastroparesis refractory to standard medical therapy (lifestyle and diet modifications, prokinetics) or contraindication to standard therapies (e.g. allergies to prokinetic agents) Patients with diabetic, idiopathic or post-surgical gastroparesis Patients with confirmed diagnosis of gastroparesis via gastric emptying study (abnormal gastric emptying will be defined as ≥10 % residual activity at 4 h on a standardized nuclear medicine TC-99 m sulfur colloid solid-phase gastric emptying study) Exclusion Criteria: Patients with prior history of gastroenteric anastomosis or any GI surgeries with pyloric involvement Patients with gastroesophageal malignancy Patients who are unable to tolerate upper endoscopy secondary to cardiopulmonary instability or other contraindications to endoscopy Patients with cirrhosis Patients who are pregnant or breastfeeding Patients with uncorrectable coagulopathy defined by INR >1.5 or platelets <50

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transpyloric stent<br>In this group, patient's will be randomized to receive a transpyloric stent for treatment of refractory gastroparesis. They will be blinded for one month after stent placement as to whether they received a stent or sham. | Device: Transpyloric stent<br>* See arm/group descriptions<br>|
| Sham Comparator: Sham<br>In this group, patient's will be randomized to sham for treatment of refractory gastroparesis. They will be blinded for one month after stent placement as to whether they received a stent or sham. | Other: Sham<br>* Sham<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response will be assessed by the gastroparesis cardinal symptom index (GCSI) scores | GCSI assessment is based off an average of 16 questions that are scored from 0-5, with higher scores indicating a worse clinical outcome. | 1-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age | Assessed in years | 1-2 years | 
| Weight | Assessed in kilograms | 1-2 years | 
| Height | Assessed in inches | 1-2 years | 
| BMI | Assessed in kg/m^2 | 1-2 years | 
| Adverse events | Assessed based on current American Society for Gastrointestinal Endoscopy (ASGE) guideline definitions for endoscopic adverse events | 1-2 years | 
| Procedure length | Assessed in minutes | intraoperative |