Gastric Electrical Stimulation for Pain in Gastroparesis

Abdominal pain affects almost 25% of the general population and results in more than 15 million clinical visits each year. Gastroparesis (Gp), defined as delayed stomach emptying and affecting 5 million American, is a major health burden with limited treatment options. About 50% of patients with Gp are on narcotics for pain, but narcotics delay gastric emptying and thus worsen symptoms of nausea and vomiting. Gastric electrical stimulation (GES) via an implantable pulse generator (a device called Enterra) has been approved by the FDA as a humanitarian method to treat nausea and vomiting in patients with Gp. However, its effect on abdominal pain is largely unknown. In this project, we propose using GES in two ways to help elucidate its role in attenuating abdominal pain: using a special set of parameters, Pp derived from pre-clinical studies, and using modified Enterra parameters, Pm derived from a clinical algorithm. Both methods will be compared with the nominal Enterra setting, Pn. During the UG3 Phase, we will modify the Enterra software to allow multiple settings at different times of a 24-h period, develop an IRB protocol, meet with FDA and obtain IRB approval for the final study protocol that incorporates inputs from FDA. During the UH3 Phase, we will conduct a 3-center randomized, double-blinded and placebo controlled clinical study to investigate the effect of the proposed GES methods (two novel parameter settings). To make such an early clinical study feasible, we will enroll only those patients with gastroparesis who are under the treatment of nausea and vomiting using an implantable Enterra device. The clinical study will be performed in 150 Gp patients with abdominal pain randomized to receive one of three treatments: GES with the nominal parameters, Pn serving as control, GES with special parameters, Pp and GES with modified Enterra parameter, Pm. The primary outcome will be the 7-day average of daily worst pain; the secondary outcomes will include change in use of pain medications, percent of responders and gastroparesis cardinal symptom index. The PI’s have assembled a comprehensive and competitive team with expertise in all areas of this research. The PIs are world leaders in neuromodulation, GES and Gp. The project is easy to implement (simply changing the parameter setting) but may lead to novel therapies for visceral pain. The likelihood of success is high due to promising preclinical findings, availability of patients and extensive experience of the team.