Use of EndoFLIP and Manometry Prior to G-POEM
Use of EndoFLIP and Manometry Prior to G-POEM
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.
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.
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