Use of EndoFLIP and Manometry Prior to G-POEM

March 14, 2024 updated by: A. Aziz Aadam, Northwestern University

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Addition of ADM and EndoFLIP to pre-G-POEM evaluation
During the preoperative upper endoscopy, the EndoFLIP catheter is inserted through the mouth with endoscopic guidance and placed through the gastric pylorus. Once deployed, water is sequentially added at set volumes to a balloon that can be used to measure pyloric diameter, cross-sectional area, pressure, and distensibility at set volumes of 30, 40, and 50 mL for at least five seconds. We will record this data for each patient. The EndoFLIP catheter will then be removed. Subsequently, a high resolution ADM catheter will be inserted through the nose and placed through the pylorus to measure baseline intragastric, transpyloric, and intraduodenal pressures. The patient will be observed for up to four hours to assess a migrating motor complex (MMC). After the MMC is observed, the patient will be given a meal and observed for meal response with the manometry catheter. The meal will be water and two pieces of toast/bread. Following the meal, the catheter will be removed.
Diagnostic test: EndoFLIP
During pre-G-POEM upper endoscopy, an EndoLIP catheter will be inserted through the patient's mouth into the stomach and across the pylorus. Once results of EndoFLIP are obtained, the catheter will be removed (5 minutes).
Diagnostic test: Antroduodenal Manometry
Following removal the EndoFLIP catheter, a manometry catheter will then be placed through the nose and advanced across the pylorus. Once catheter positioning is confirmed on endoscopy, the endoscope will be withdrawn. The manometry catheter will be taped to the nose and sedation stopped. The patient will be brought to the recovery area where they will wake-up with the catheter in place. In a private recovery room, the patient will have the catheter in place (no positioning or movement restrictions). When pyloric spasms are documented (0.5-4 hours), they will be given a standard small meal (water, toast/bread). Once motility is assessed with eating, the manometry catheter will be removed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive Value of EndoFLIP
Time Frame: 24 months
To assess the predictive value of EndoFLIP for clinical response to G-POEM in patients with refractory gastroparesis. We hypothesize that patients with lower pyloric distensibility (measured in mm2/mmHg) will be predictive of clinical response to G-POEM.
24 months
Predictive Value of ADM
Time Frame: 24 months
To assess the predictive value of high resolution ADM for clinical response to G-POEM in patients with refractory gastroparesis. We hypothesize that patients with a large, positive pressure gradient will be predictive of clinical response to G-POEM.
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EndoFLIP data correlation
Time Frame: 24 months
To evaluate correlations between EndoFLIP pressure and distensibility and ADM transpyloric pressure and intragastric-intraduodenal pressure gradient. We hypothesize that there will be significant negative correlation between pyloric distensibility and the intragastric-intraduodenal pressure gradient.
24 months
Quality of Life outcome of G-POEM
Time Frame: 36 months
To further assess quality of life changes following G-POEM using Patient Assessment of Upper GI Symptoms (PAGI-SYM) questionnaire
36 months
Quality of Life outcome assessed by SF-36 QOL survey questionnaire
Time Frame: 36 months
36 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 36 months
To monitor for adverse associated with G-POEM
36 months
Gastric-Emptying Characteristics
Time Frame: 36 months
To assess changes in Gastric-Emptying Studies pre-procedure and post-procedure in percentage emptied at 4 hours
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2021

Primary Completion (Actual)

March 1, 2024

Study Completion (Actual)

March 1, 2024

Study Registration Dates

First Submitted

March 11, 2021

First Submitted That Met QC Criteria

April 13, 2021

First Posted (Actual)

April 14, 2021

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00213007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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