Mechanisms of Action for the Enterra Medical Gastric Electrical Stimulator
NCT Number: NCT06582576
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Gastroparesis|Vomiting|Nausea
Interventions: DIAGNOSTIC_TEST: Effect of different gastric electrical stimulator stimulation paragdimes on brain, heart, and stomach.
Sponsor: University of Aarhus
Collaborators: Aalborg University Hospital|Aarhus University Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-08-20
Completion Date: 2025-10-01
Locations: Department of hepatology and gastroenterology, Aarhus University Hospital, Aarhus N, 8200, Denmark

Summary:
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.

Primary Outcome Measures: Evoked brain potentials, Amplitude of evoked brain potentials induced by gastric electrical stimulation, 5min during maximum stimulation intensity
Secondary Outcome Measures: EEG measures between ON/OFF stimulation, EEG frequency distribution when comparing the OFF and ON stimulation modes, 5min|Meal-related EEG measures, EEG frequency distribution in response to an ingested meal when comparing the OFF and ON stimulation modes., 5min|ECG measures between ON/OFF stimulation, 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, Heart rate variability, periodic repolarisation dynamic, and the deceleration capacity of the heart rate following different stimulation intensities., 5min|Meal-related ECG measures, 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, Gastric accommodation in response to an ingested meal comparing OFF and ON stimulation., 5min|Meal-related gastric tension, Gastric tension in response to an ingested meal comparing OFF and ON stimulation., 5min|Meal-related gastric contraction frequency, Gastric contraction frequency in response to an ingested meal comparing OFF and ON stimulation., 5min|Symptoms and gastric measures, Correlation between gastroparesis symptoms (Gastroparesis Cardinal Symptom Index) and changes in gastric accommodation/tension when turning the stimulation ON after meal ingestion., 5min