Mechanisms of Action for the Enterra Medical Gastric Electrical Stimulator

August 30, 2024 updated by: University of Aarhus

Investigation of the Putative Mechanisms Underlying the Symptom-lowering Effect of the Enterra Medical Gastric Electrical Stimulator for Gastroparesis Treatment

Background: Gastric electrical stimulation applied by a surgically implanted device effectively alleviates upper gastrointestinal symptoms in the majority of individuals with medically refractory gastroparesis. Despite its efficacy, the mechanisms of action have been minimally explored in previous studies, and it is unknown why some individuals experience limited symptom-lowering effects.

Aim: We aim to investigate two of the potential mechanisms of action leading to symptom-reducing effects of gastric electrical stimulation: 1) possible central effects in the brainstem and brain by enhanced parasympathetic vagal activity, and 2) peripheral effects in the stomach by improved gastric accommodation.

Methods: Up to thirty individuals with drug-refractory gastroparesis having an implanted gastric electrical stimulator will be enrolled in this cross-sectional and observational study. Of these, 15 will be responders (substantial symptomatic improvement) and 15 non-responders (minor symptomatic improvement). Electroencephalography (EEG) will evaluate the stimulation-induced activity in the brain and brainstem to assess whether the gastric stimulation generates evoked potentials. Electrocardiography (ECG) will investigate stimulation-induced changes in the autonomic regulation of the heart. Gastric ultrasound will investigate the effect of stimulation on stomach accommodation, contractions, and wall tension. These central and peripheral measures will be assessed during one study day before and after activating the gastric electrical stimulator, following an increase in stimulation intensity and post-meal consumption. Furthermore, results will be compared between responders and non-responders.

Perspectives: Adjusting the parameters of gastric electrical stimulation based on objective markers in the brain, heart, or stomach, rather than relying on symptom fluctuations, may enhance the effectiveness of symptom improvement. In the future, these objective markers may aid in differentiating between responders and non-responders, which may lead to optimised selection criteria for surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

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

Study Contact

Study Contact Backup

  • Name: Asbjørn Drewes, MD
  • Phone Number: 29465969
  • Email: amd@rn.dk

Study Locations

  • Denmark
      • Aarhus N, Denmark, 8200
        • Recruiting
        • Department of Hepatology and Gastroenterology, Aarhus University Hospital
        • Contact:
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Individuals having an implanted Enterra gastric electrical stimulator for treating gastroparesis. 15 will be included as "responders" and 15 as "non-responders". Using a 5-point Likert scale, each participant will evaluate the experienced symptom-reducing effect of the gastric electrical stimulation. The individuals answering 0 or 1 (minor or no symptom improvement) are defined as responders, while individuals answering 3 or 4 (substantial or full symptom improvement) are defined as responders. Individuals answering 2 will not be included in the study.

Description

Inclusion Criteria:

  • Age 18 and above
  • Able to read and understand Danish
  • Have an implanted gastric electrical stimulator for treating gastroparesis
  • Answering 0 or 1 (non-responders) or 3 or 4 (responders) on the Likert scale describing the symptom improvement gained by gastric electrical stimulation.
  • Personally signed and dated the informed consent documents ("Informeret samtykke") indicating that the patient has been informed of all pertinent aspects of the trial
  • Are willing and able to comply with the scheduled visit and trial procedures

Exclusion Criteria:

  • Previous surgery on the vagus nerve, including cervical vagotomy
  • Prior thoracic, abdominal or brain surgeries that, in the opinion of the investigator, could limit data collection or interpretation.
  • Previous diagnosis or history of orthostatic intolerance, e.g. POTS, neurocardiogenic syncope, orthostatic hypotension or autonomic dysfunction.
  • Patients with an implanted cardiac device (e.g. pacemaker, CRT, etc.) or vagal nerve stimulator (VNS).
  • History of neurological disease that, in the opinion of the investigator, could limit data collection or interpretation.
  • Participants with any clinical abnormalities that, in the opinion of the investigator, may increase the risk associated with trial participation or may interfere with the interpretation of the trial results

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Responders
Individuals who have a gastric pacemaker for treating gastroparesis and answered that they have experienced a "substantial or full" symptomatic improvement after the implantation.
Diagnostic test: Effect of different gastric electrical stimulator stimulation paragdimes on brain, heart, and stomach.
Measuring EEG, ECG, and ultrasound in both groups during different stimulation intensities provided by their previously implanted gastric electrical stimulator.
Non-responders
Individuals who have a gastric pacemaker for treating gastroparesis and answered that they have experienced "some or none" symptomatic improvement after the implantation.
Diagnostic test: Effect of different gastric electrical stimulator stimulation paragdimes on brain, heart, and stomach.
Measuring EEG, ECG, and ultrasound in both groups during different stimulation intensities provided by their previously implanted gastric electrical stimulator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evoked brain potentials
Time Frame: 5min during maximum stimulation intensity
Amplitude of evoked brain potentials induced by gastric electrical stimulation
5min during maximum stimulation intensity

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
EEG measures between ON/OFF stimulation
Time Frame: 5min
EEG frequency distribution when comparing the OFF and ON stimulation modes
5min
Meal-related EEG measures
Time Frame: 5min
EEG frequency distribution in response to an ingested meal when comparing the OFF and ON stimulation modes.
5min
ECG measures between ON/OFF stimulation
Time Frame: 5min
Heart rate variability, periodic repolarisation dynamic, and the deceleration capacity of the heart rate when comparing the OFF and ON stimulation modes.
5min
ECG measures between stimulation intensities
Time Frame: 5min
Heart rate variability, periodic repolarisation dynamic, and the deceleration capacity of the heart rate following different stimulation intensities.
5min
Meal-related ECG measures
Time Frame: 5min
Heart rate variability, periodic repolarisation dynamic, and the deceleration capacity of the heart rate in response to an ingested meal when comparing the OFF and ON stimulation modes.
5min
Meal-related gastric accomodation
Time Frame: 5min
Gastric accommodation in response to an ingested meal comparing OFF and ON stimulation.
5min
Meal-related gastric tension
Time Frame: 5min
Gastric tension in response to an ingested meal comparing OFF and ON stimulation.
5min
Meal-related gastric contraction frequency
Time Frame: 5min
Gastric contraction frequency in response to an ingested meal comparing OFF and ON stimulation.
5min
Symptoms and gastric measures
Time Frame: 5min
Correlation between gastroparesis symptoms (Gastroparesis Cardinal Symptom Index) and changes in gastric accommodation/tension when turning the stimulation ON after meal ingestion.
5min

Collaborators and Investigators

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

Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital
Aalborg University Hospital

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 (Estimated)

August 20, 2024

Primary Completion (Estimated)

October 1, 2025

Study Completion (Estimated)

October 1, 2025

Study Registration Dates

First Submitted

August 30, 2024

First Submitted That Met QC Criteria

August 30, 2024

First Posted (Actual)

September 3, 2024

Study Record Updates

Last Update Posted (Actual)

September 3, 2024

Last Update Submitted That Met QC Criteria

August 30, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GES - mechanisms of action

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The final dataset can be provided upon reasonable request

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.

No

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.

Clinical Trials on Nausea

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in France

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe