GPOEM Versus SHAM as a Treatement of Gastroparesis (GPOEMvsSHAM)

A Prospective Single Blinded Randomized SHAM Efficacy Study of Gastric Per Oral Endoscopic Pyloromyotomy (G-POEM) as a Treatment of Gastroparesis

Objectives: To evaluate the efficacy of gastric per oral endoscopic pyloromyotomy (G-POEM) in the treatment of gastroparesis.

Endpoints Primary endpoint: Clinical Efficacy Will be assessed by measurements of Gastroparesis Cardinal Symptoms Index (GCSI) score, Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the 36-Item Short Form Health Survey (SF-36). Outcome criteria will be measured at baseline, 1 month, 5 months, 7 months and 12 months. These criteria will be the mean total GCSI score, and SF-36 score based on the values recorded with a Likert scale. GES parameters will be the half gastric emptying time and the RPH2.

Secondary endpoint: Safety Safety will be characterized by the incidence of all Adverse Device Effects (ADEs), non-serious and serious, possibly related to or related to the procedure and/or device that are experienced by study participants.

In addition, safety assessments will be determined based on physical examination (vital signs) and laboratory tests during scheduled visits. Safety evaluations will also be performed to ensure no subsequent adverse events have occurred and to ensure any adverse events during the trial that are considered on-going are stable or have resolved. Safety will be assessed at 1 month, 5 months, 7 months and 12 months following the intervention.

Other secondary endpoints will be technical success, nutritional status assessed by the measurement of the BMI, pre-albumin and albumin levels and for diabetics the HbA1c. These criteria will be measured at baseline, 1 month, 5 months, 7 months and 12 months.

Overall design This will be a prospective, sham-randomized, monocentric, interventional, efficacy study.

Once baseline eligibility criteria have been met, a first endoscopy under general anesthesia is proposed to the patients. Patients will be randomized blindly in a 1/1 fashion design between the sham arm and the GPOEM arm. At the time of the general anesthesia, a sealed envelope will be opened. Subjects will have a second endoscopy under general anesthesia 6 months later and the sham arm will then beneficiate from a GPOEM procedure and the GPOEM arm a sham procedure. Then, all the patients will be followed for another 6 months.

GCSI score, PAGI-SYM, SF36 will be collected at screening, 1,5,7 and 12 months. GES RPH2, RPH4 and half emptying time will be collected at screening, 5 months and 12 months.

Study procedures

Description procedure in the GPOEM arm:

The intervention will be performed under general anesthesia with tracheal intubation in supine position. GPOEM is performed with the following steps: -i: submucosal injection; -ii: mucosal incision upstream the pylorus followed by submucosal tunneling; -iii: antropyloromyotomy; -iv: closure of the tunnel access.

Description procedure in the SHAM arm:

A diagnostic upper digestive tract endoscopy will be performed under general anesthesia with tracheal intubation in supine position, injection of 1 cc of saline at four quadrants of the pylorus.

Post-operative management Once the patients recovered from anesthesia after the procedure, they were administrated analgesics and anti-emetics as needed and esomeprazole 80 mg daily systematically to protect the mucosal access and tunnel from ulceration. Patients will be kept fasted for the first postoperative day (POD 1). In the absence of adverse events, patients will be allowed to resume liquid oral intake for 1 day, a soft-ground diet for 2 additional days, and finally a normal diet. They will be discharged after POD 1 in the absence of adverse events, with a prescription of esomeprazole 40 mg daily by mouth for 1 month and dietary instructions.

After 6 months, another endoscopy under general anesthesia will be performed with the SHAM and GPOEM arms are interchanged.

After the G-POEM / SHAM procedure, all patients will be rigorously evaluated in the same fashion. They will be assessed clinically before being discharged (POD 1) and then at 1 month and 5 months after the intervention with a clinical examination that included determination of the severity of the symptoms and total GCSI score, PAGI-SYM, SF-36. A GES will be performed at 5 months and 12 months.

Study Overview

• Status: Unknown
• Conditions: Gastroparesis
• Intervention / Treatment: Other: GPOEM; Other: SHAM Procedure

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • Recruiting
    • Gastroenterology Department, Erasme University Hospital
    • Contact: Hubert LOUIS, MD; Phone Number: +32 2 555 5721; Email: hubert.louis@erasme.ulb.ac.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18-64 years;
2. Severe refractory gastroparesis based on the presence of delayed gastric emptying-related symptoms, including nausea, retching, vomiting, abdominal pain, stomach fullness, early satiety, loss of appetite, postprandial fullness, and/or bloating. Dominant symptoms being nausea and vomiting.
3. Severe refractory disease defined by symptoms related to gastroparesis with associated weight loss, failure or recurrence in patients who received available optimal pharmacologic therapies and a Gastroparesis Cardinal Symptoms Index (GCSI) score > 2.3 (calculated as mean of total subscores).
4. Recent (<3 months) upper endoscopy showing no evidence of ulcerative lesions or gastric outlet obstruction
5. Having delayed gastric emptying as defined by a disturbed gastric emptying scintigraphy (GES) study (half emptying time > 100 min).
6. Must be able to comply with all study requirements for the duration of the study as outlined in the protocol. This includes complying with the visit schedule as well as study specific procedures such as: clinical assessment, endoscopy, radiography, as well as laboratory investigations.
7. Must be able to understand and be willing to provide written informed consent.

Exclusion Criteria:

1. Achalasia and any other esophageal motility disorders.
2. Heart diseases: unstable angina, myocardial infarction within the past year, or heart disease classified within the New York Heart Association's Class III or IV functional capacity.
3. Hypertension: uncontrolled hypertension during last 3 month.
4. Severe renal, hepatic, pulmonary disease or cancer.
5. Gastrointestinal stenosis or obstruction.
6. Pregnancy or breastfeeding.
7. Impending gastric surgery 60 days post intervention.
8. Peptic ulcer disease or tumoral lesion at endoscopy.
9. Normal gastric emptying scintigraphy.
10. Presence of coagulation disorders (TP < 50% and/or platelets < 50 G/l), or anesthesiologist exclusion.
11. The chronic use of opioids.
12. Currently participating in other study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: SHAM	Other: SHAM Procedure; intrapyloric injection of saline solution
Active Comparator: GPOEM	Other: GPOEM; gastric per oral endoscopic pyloromyotomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Efficacy will be defined by a decrease of a total Gastroparesis Cardinal Symptom Index (GCSI) symptom score of at least 0.75 points from the baseline total score of GCSI	12 months
Assessment of Gastrointestinal Disorders Symptom Severity Index	Will be assessed by the significant improvement of the Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), clinical score from baseline	12 months
Quality of life	Quality of Lige will be assessed by the significant improvement of the 36-Item Short Form Health Survey (SF-36), clinical score from baseline	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastric Emptying Scintigraphy improvement	We will assess significant improvement Gastric Emptying Scintigraphy (GES) parameters from baseline	12 months
Safety	Safety will be characterized by the incidence of all Adverse Device Effects (ADEs), non-serious and serious, possibly related to or related to the procedure and/or device that are experienced by study participants	12 months

Collaborators and Investigators

• Sponsor: Erasme University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): September 17, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neurologic Manifestations; Gastrointestinal Diseases; Stomach Diseases; Paralysis; Gastroparesis
• Other Study ID Numbers: P2017/334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No