Clinical trial NCT04844190: Use of EndoFLIP and Manometry Prior to G-POEM
Official title: Use of Endoscopic Functional Lumen Imaging Probe (EndoFLIP) and Antroduodenal Manometry (ADM) in Predicting Clinical Response to Gastric Peroral Endoscopic Myotomy (G-POEM): A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Gastroparesis
Keywords: G-POEM
High Resolution Manometry
Endoscopic Functional Lumen Imaging Probe
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2021-04-14
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective Study
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to assess physiologic response of therapy in patients with refractory gastroparesis undergoing Gastric per-oral endoscopic myotomy (G-POEM) using endoscopic functional lumen imaging probe (EndoFLIP) and antroduodenal manometry (ADM). Refractory gastroparesis will be defined as having delayed gastric emptying at four hours (\>10% retention of stomach contents) on gastric scintigraphy and persistent symptoms despite treatment with dietary modification or prokinetic medications. We hypothesize that EndoFLIP and high resolution ADM will provide an individualized pyloric functional profile in gastroparesis patients that can more accurately predict clinical response to G-POEM.

Detailed description: Gastroparesis is defined as an objective delay in gastric emptying in the absence of mechanical obstruction with corresponding cardinal symptoms of postprandial fullness, early satiety, nausea, vomiting, bloating, and abdominal pain. Gastroparesis-related hospitalizations have increased by 158% in recent years as healthcare costs associated with gastroparesis have similarly risen exponentially by 1026% from 1997 to 2013.

Medical management of gastroparesis, primarily comprised of dietary and prokinetic therapy, is limited in effectiveness, tolerability, and durability, in part because the pathophysiologic mechanisms underlying gastroparesis are varied and multifactorial, including pyloric dysfunction, impaired fundic accommodation, vagal injury or neuropathy, gastric pacemaker dysrhythmias, hypocontractility, and aberrant gastric feedback. Pyloric dysfunction in particular, characterized by increased tone or pylorospasm, offers the potential for targeted endoscopic therapy in a subset of patients.

Gastric peroral endoscopic myotomy (G-POEM) has recently emerged as a feasible and safe treatment for severe refractory gastroparesis. Initially described in 2013, G-POEM is a minimally invasive technique that consists of creating a submucosal tunnel extending to the pylorus, dissecting circular and oblique muscle layers, and closing the tunnel with endoscopic clips. The first systematic review of early outcomes of G-POEM across 10 studies and 292 patients revealed 100% technical success, symptomatic improvement in 84%, and an adverse event rate of 6.8%.

However, a nuanced approach to appropriate patient selection for G-POEM, based on individual physiologic characteristics, is still lacking. The endoscopic functional lumen imaging probe (EndoFLIP; Crospon Inc., Galway, Ireland), previously well-described in assessing the lower esophageal sphincter in esophageal motility disorders, has been recently proposed as an adjunctive technology for evaluating pyloric sphincter compliance and distensibility. Few studies have investigated the efficacy of pyloric EndoFLIP in gastroparesis. Gourcerol et al. reported that gastroparesis patients have lower pyloric compliance compared to healthy volunteers, which also correlated with longer gastric emptying half times and reduced quality of life scores. A second pilot study of 20 gastroparesis patients who underwent pre- and post-myotomy EndoFLIP revealed that a distensibility index of \<9.2 mm2/mmHg was associated with G-POEM clinical efficacy, however the study was limited by a short follow-up time of three months.

Antroduodenal manometry (ADM) has been the gold standard of assessing pyloric function and early studies revealed elevated pyloric pressures in greater than 50% of diabetics with gastroparesis. Recent data also shows a significant correlation between manometric and EndoFLIP pressures, though to date, no studies have utilized ADM in evaluating the efficacy of G-POEM. While conventional ADM was previously felt to be technically challenging and limited in availability, the advancement of high resolution manometry presents a unique opportunity for complementary assessment of not only pyloric pressures, but also antroduodenal pressure gradients.

We propose that the use of both EndoFLIP and high resolution ADM will provide an individualized pyloric functional profile in gastroparesis patients that can more accurately predict clinical response to G-POEM. As one of only few nationwide centers performing G-POEM, Northwestern Medicine has one of the highest volumes of this novel endoscopic treatment, having successfully completed 40 procedures within the last year.

Adult patients with refractory gastroparesis will be enrolled in this prospective study. Refractory gastroparesis will be defined as having delayed gastric emptying at four hours (\>10% retention) on gastric scintigraphy and persistent symptoms despite treatment with dietary modification or prokinetic medications. Preoperatively, patients will complete validated symptom and quality of life questionnaires, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and Short Form 36 (SF-36). Patients will also complete an upper gastrointestinal series (UGIS) to evaluate the anatomy of the stomach. Patients will then undergo study protocol including G-POEM. Patients will be required to follow-up at one, three, and six months in clinic or via telephone visit following G-POEM to evaluate clinical response, identify any adverse events related to the procedure, and complete symptom and quality of life questionnaires. Per standard of care, repeat gastric scintigraphy will be obtained at three months following G-POEM and will be shared with study staff. The endpoints for this study following completion of 20 G-POEM procedures are:

Primary endpoint: To assess the predictive value of EndoFLIP for clinical response to G-POEM in patients with refractory gastroparesis. Clinical response will be defined as a decrease of 1 point in the average total GCSI score, comprised of a 6-point scoring system with 9 questions from 3 cardinal subscales, with more than 25% decrease in at least 2 of 3 subscales (nausea/vomiting, postprandial fullness/early satiety, and bloating).

Secondary endpoints: To assess the predictive value of high resolution ADM for clinical response to G-POEM in patients with refractory gastroparesis. Mean intragastric-intraduodenal pressure gradients averaged over one minute within a deflated stomach during upper endoscopy will be calculated for each patient.

To evaluate correlations between EndoFLIP pressure and distensibility and ADM transpyloric pressure and intragastric-intraduodenal pressure gradient.

Additional secondary endpoints include assessment of quality of life, objective gastric emptying, UGIS results, technical success of G-POEM, procedure time, and adverse event rate.

Eligibility criteria: Inclusion Criteria:

* All patients aged 18+ diagnosed with refractory gastroparesis as defined earlier in this document, no age limit
* Patients already consented to undergo G-POEM

Exclusion Criteria:

* Patients who are pregnant(at Northwestern, all female patients have urine pregnancy tests on day of endoscopy), vulnerable populations such as prisoners,
* Life expectancy \< 1 year based on concurrent comorbidities based on study team assessment,
* Coagulopathy with INR \> 1.5 that cannot be reversed,
* Thrombocytopenia with platelets \< 50,000 that cannot be corrected with blood products,
* Unable to safely undergo elective endoscopy due to current comorbidities, and inability to pass standard endoscope.
* Patients with history of gastric surgery and
* Active narcotic use at time of G-POEM evaluation within four weeks. Tobacco use is not an exclusion criterion

Primary outcomes:
measure: Predictive Value of EndoFLIP
timeFrame: 24 months
measure: Predictive Value of ADM
timeFrame: 24 months
Secondary outcomes:
measure: EndoFLIP data correlation
timeFrame: 24 months
measure: Quality of Life outcome of G-POEM
timeFrame: 36 months
measure: Quality of Life outcome assessed by SF-36 QOL survey questionnaire
timeFrame: 36 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 36 months
measure: Gastric-Emptying Characteristics
timeFrame: 36 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
References:
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