Chronic Nausea and Vomiting in Patients With Normal Gastric Emptying Using the Enterra® Therapy System (NAVIGATE)

Inclusion Criteria:

• Willing and able to complete the informed consent process

• Stated willingness to comply with all study procedures and availability for theduration of the study

• Aged ≥18 years at time of informed consent

• Chronic, drug-refractory nausea that: a) has been present for more than 6 months,and b) has been active within the last 3 months prior to consent

• Patient is able to complete ANMS GCSI-DD surveys on a compatible smart device with:a) a minimum of four (4) ANMS GCSI-DD entries per week for two consecutive weeks,and b) an average ANMS GCSI-DD score for nausea severity of ≥2.5 during the sametwo-week period

• Refractory or intolerant to two or more of the following antiemetic drug classes:antihistamines, phenothiazines, serotonin type 3 receptor antagonists, dopamine type 2 receptor antagonists, anticholinergics, neurokinin receptor antagonists

• Medically stable, in the opinion of the investigator, during the month prior toconsent, with no planned modifications to medical therapy during the course of thestudy

• Normal gastric emptying as assessed by a qualifying gastric emptying test performedwithin 2 years of consent if no prior pyloric transection therapy, or within 2 yearsof consent and after the most recent pyloric transection therapy

• Normal upper endoscopy within 1 year prior to consent (e.g., absence ofobstructions, ulcers, or cancers in the esophagus, stomach, or duodenum) performedwithin 1 year of consent if no prior pyloric transection therapy, or within 1 yearof consent and after the most recent pyloric transection therapy

Exclusion Criteria:

• Cognitive impairment or other characteristic that would limit a patient's ability tocomplete study requirements

• Pyloric transection therapy completed within 1 year of consent

• Documented gastrointestinal (GI) obstruction or pseudo-obstruction

• History of primary swallowing disorders

• History of primary psychogenic vomiting

• History of primary eating disorder

• History of cyclic vomiting syndrome

• History of rumination syndrome

• History of scleroderma

• History of amyloidosis

• History of cannabis hyperemesis syndrome

• Active H. pylori infection

• Evidence of bezoar during most recent endoscopy

• Previous gastric surgery of any type other than a pyloric transection therapy (i.e.,pyloroplasty, pyloromyotomy, POP, or G-POEM)

• Uncontrolled thyroid disorder, in the opinion of the investigator

• History of seizures disorders

• Hemoglobin A1c >8.0%

• Peritoneal dialysis or unstable hemodialysis

• Parenteral or enteral nutritional support

• Active pancreatitis

• History of organ transplant, gross malabsorptive syndromes, celiac disease, orinflammatory bowel disease

• Other GI tract diseases and disorders that the investigator believes may have causedthe patient's drug-refractory nausea and/or vomiting

• Malignancy (with the exception of basal cell carcinoma of the skin) currentlypresent, initially diagnosed or recurring within 5 years of consent

• Opioid use

• Current cannabis/cannabinoid use that exceeds: 3 days of usage per week, or 2occurrences during each day of use, or 3 grams of total usage per week

• Heavy alcohol use, defined as: for men, consuming five or more drinks on any day or 15 or more per week; for women, consuming four or more drinks on any day or 8 ormore per week

• Injection of Botox into the pyloric sphincter within 6 months of consent

• Active major levels of anxiety/depression, as determined by the investigator

• History of other clinically significant disease, or any other condition which, inthe opinion of the Investigator, would jeopardize the safety of the patient orimpact the validity of the study results

• Life expectancy <1 year

• Pregnant or breastfeeding at the time of consent or intend to become pregnant duringthe study

• Any underlying disease leading to follow-up by MRI outside of current MR conditionalindications

• Glucagon-like peptide 1 (GLP-1) agonist drug use within 6 months of consent

• Participation in other investigational clinical studies

• Existing or prior gastric electrical stimulator implantation