Safety and Effectiveness of eGERD Device to Reduce Gastroesophageal Reflux Disease (GERD) Symptoms

The Effect of Non-Invasive Electrical Stimulation Therapy on Gastroesophageal Reflux Disease (GERD)

The purpose of this research is to evaluate the safety and effectiveness of the eGERD device, which is a novel device for treating Gastroesophageal Reflux Disease (GERD).

The main questions this research aims to answer are:

1. Does the eGERD device reduce acidity in the esophagus?
2. Does the eGERD device reduce GERD symptoms such as heartburn and regurgitation?
3. What medical problems do participants have when using the eGERD device?

To assess the acidity in the esophagus, a wireless standard-of-care capsule called Bravo will be placed in the participants esophagus (throat) for several days.

To assess GERD symptoms, participants will be requested to report symptoms they experience using a smartphone application.

Researchers will compare a real version of the eGERD device to a sham version (a look-alike device that has no therapeutic effect) to see if the eGERD device is effective in treating GERD.

The study includes two consecutive phases: a 14-day washout phase followed by a 28-day device treatment phase.

The washout phase starts on or shortly after the Screening visit, in which the participants sign the informed consent form (ICF) and their eligibility criteria are assessed. The first day of the washout phase is considered Day 1 of the study.

In the washout phase, participants are instructed to avoid any GERD-treatment medications (including antacids), either prescribed or over-the-counter (OTC), and to keep their regular daily routines.

Participants are also instructed to report occurrence and severity of GERD-related symptoms using the eGERD smartphone application.

GERD-HRQL questionnaire are filled at the onset (Day 1) and at the end (Day 14) of this phase. Questionnaire score obtained at the end of the washout phase (QoL Score baseline) are regarded as baseline for the QoL secondary endpoint.

On the last day of the washout phase (Day 14), a 24h wireless pH monitoring test (Bravo) is initiated, in order to obtain acid exposure time (AET) and DeMeester score (DM) baseline levels.

The device treatment phase consists of continuous usage of the study device for 28 days.

At the onset of the device treatment phase, the pH monitoring data is downloaded and analyzed, to establish AET and DM baseline levels. To be eligible for randomization and study device usage, a participant must have (i) at least 18 hours of baseline monitoring data , and (ii) abnormal baseline AET (above 6%). Ineligible subjects are classified as screen failures. participants with insufficient baseline monitoring data (less than 18 monitoring hours) are offered to extend the baseline monitoring for another 24 hours.

Upon establishing participant eligibility and performing randomization, a new 96h wireless pH monitoring test is initiated using the same Bravo capsule already in place. At the same time, the participant starts using the study device. One day later, a short clinic visit is held in which proper operation of the study device is verified. At the end of the 96h pH monitoring test, the monitoring system is collected and the data downloaded.

Usage of the study device is continued from randomization for 28 days. Esophageal acid exposure time (AET) and DeMeester score (DM) obtained from the 24h wireless pH monitoring test are regarded as baseline for AET primary endpoint and DeMeester score secondary endpoint, respectively.

Esophageal acid exposure time and DeMeester score obtained from the last Complete Monitoring Day of the 96h monitoring test are considered AET primary endpoint and DeMeester score secondary endpoint, respectively.

Throughout this phase, participants are using a study device (either functional or sham), after receiving instructions on its usage. Participants are instructed to use the study device 24 hours per day, 7 days per week (excluding device charging, bathing, sporting, private situations, etc.).

Usage of antacids (Gaviscon Regular Strength antacid tablets, 2-4 tablets, up to 4 times a day) as a rescue treatment is allowed after the Bravo system has been collected from the participant (Day 19). Rescue treatment usage is reported and recorded. Usage of any other type of GERD-treatment is prohibited throughout the entire phase.

GERD-HRQL questionnaire is filled at the end of this phase (or on end-of-study visit, in case of early termination). Resulting score is regarded as QoL secondary endpoint.

Inclusion Criteria:

1. Male or female, aged 22 - 75
2. Has been typically suffering from at least three heartburn and/or regurgitation episodes per week during the past three months.
3. Undergone a wireless (Bravo) pH monitoring test during the past 24 months prior to enrollment into the current study, following a 7-day (min.) off-PPI period, with AET ≥6% (as defined in section 7.2) in at least 2 monitoring days AND when averaged over all monitoring days of the test; or, in the absence of such testing, has been determined by the Principal Investigator (PI), based on a detailed anamnesis and with written agreement from the Medical Director, to have gastroesophageal reflux disease (GERD) other than functional GERD; or Undergone a catheter-based pH monitoring test during the past 24 months prior to enrollment into the current study, following a 7-day (min.) off-PPI period, with AET ≥6% (as defined in section 7.2); or, in the absence of such testing, has been determined by the Principal Investigator (PI), based on a detailed anamnesis and with written agreement from the Medical Director, to have gastroesophageal reflux disease (GERD) other than functional GERD.
4. Able and willing to give informed consent for participation in the study and to comply with all study requirements, including operating the smartphone application.
5. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.

Exclusion Criteria:

1. Previously undergoing gastric or esophageal surgery
2. Active peptic ulcer disease or symptomatic helicobacter
3. Esophageal or gastric varices or esophageal peptic stricture
4. Severe dysphagia
5. History of suspected or confirmed esophageal or gastric cancer
6. History of any other malignancy in the last 2 years
7. Pregnant women or women intending to become pregnant during the trial period
8. Uncontrolled diabetes mellitus, defined as HbA1c > 7.5%
9. Severe cardiac conditions such as cardiac arrhythmia or ischemia or cardiac pacemaker / defibrillator
10. Having any implanted electrical device (e.g. sacral nerve stimulation, brain stimulator, others)
11. Known allergy to the device's adhesives/patches
12. Severe pulmonary diseases
13. History of significant multisystem diseases (e.g. kidney failure, liver failure)
14. Known autoimmune or a connective tissue disorder (e.g. scleroderma, CREST-syndrome, Sjogren's Syndrome), requiring therapy in the preceding 2 years
15. History of Barrett's esophagus
16. Para-esophageal hiatal hernia
17. Known history of sliding hiatal hernia ≥4 cm in the last 3 years
18. Known history of erosive esophagitis Grade C or D (LA classification) in the past 5 years
19. Obesity, defined as BMI>32
20. History of gastroparesis
21. History of fibromyalgia, epilepsy, endometriosis
22. Umbilical hernia >3cm
23. Past usage experience with the study device
24. Those currently enrolled in any other interventional clinical study
25. Inability to sign the informed consent
26. Inability to understand and fill the reports and questionnaires included in the study
27. Inability to follow the study requisites
28. Other medical conditions/medications that would interfere with subject safety or data collection in the opinion of the PI