Enterra Therapy for Nausea and Vomiting

(NAVIGATE Trial)

Recruiting at 11 trial locations

Overseen By John Wo, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Enterra Medical, Inc.

Must be taking: Antiemetics

Must not be taking: Opioids, GLP-1 agonists

Disqualifiers: Delayed gastric emptying, GI obstruction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

148 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the Enterra Therapy System, a medical device, can reduce nausea and vomiting and improve quality of life for people with chronic nausea. It targets individuals who have experienced nausea for over six months and have tried at least two types of nausea medications without success. Participants will be divided into two groups: one group will have the device turned on, while the other will have it turned off initially, with adjustments made over time. Those struggling with persistent nausea and ineffective medications might find this trial suitable. As an unphased trial, this study offers a unique opportunity to contribute to understanding how this device can aid those with chronic nausea.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that there are no planned changes to your medical therapy during the study. It's best to discuss your specific medications with the study team.

What prior data suggests that the Enterra Therapy System is safe for treating chronic nausea?

In a previous study, the Enterra Therapy System reduced vomiting by 67.8% over 12 months, meaning patients vomited much less often. The study also found that the treatment was generally well-tolerated, with most people not experiencing serious side effects.

Another study showed that 54% of patients experienced more than a 50% improvement in their nausea and vomiting symptoms, suggesting that many felt better with the treatment.

The FDA has already approved the Enterra Therapy System for treating stomach issues like chronic nausea and vomiting, indicating it is safe enough for use in these conditions.

Overall, the treatment appears safe and has a good track record of reducing symptoms without major problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Enterra Therapy System is unique because it offers an innovative approach to managing nausea and vomiting through electrical stimulation. Unlike traditional treatments like antiemetic medications that work chemically to reduce nausea, Enterra Therapy uses a small device implanted in the stomach to send mild electrical pulses. This method targets the stomach directly and can be adjusted for personalized therapy, offering a potential solution for patients who do not respond well to medications. Researchers are excited about this treatment because it has the potential to provide relief when other options fall short, and it allows for tailored adjustments based on individual patient needs.

What evidence suggests that the Enterra Therapy System is effective for reducing nausea and vomiting?

Research has shown that the Enterra Therapy System can help reduce nausea and vomiting. In one study with 50 patients, 54% experienced more than a 50% improvement in their symptoms. Another study found that individuals with gastroparesis—a condition where the stomach doesn't empty properly—also experienced significant relief from nausea and vomiting. Additionally, many patients reported satisfaction with the results: 87.1% felt satisfied with their symptom improvement after one year, and 79.7% remained satisfied after five years. In this trial, participants will join either the ON Group, where the device is actively programmed, or the OFF Group, where the device is initially set to off. These findings suggest that Enterra Therapy could reduce symptoms and improve the quality of life for those with ongoing nausea. ^{1 2 6 7 8}

Who Is on the Research Team?

Jason Hamann, PhD

Principal Investigator

Enterra Medical, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic nausea (with or without vomiting) that's lasted more than 6 months and has been active in the last 3 months. They must have normal gastric emptying, no changes to medical therapy planned, and be medically stable. Participants need a recent normal upper endoscopy and must not respond to two types of antiemetic drugs.

Inclusion Criteria

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

Normal upper endoscopy within 1 year prior to consent (e.g., absence of obstructions, ulcers, or cancers in the esophagus, stomach, or duodenum)

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 same two-week period

Exclusion Criteria

History of cannabis hyperemesis syndrome

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

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants have the Enterra® Therapy System implanted and are assigned to either the ON or OFF treatment group. Device programming values may be adjusted at follow-up study visits.

8 months

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, with adjustments to device programming as needed.

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Enterra Therapy System

Trial Overview The NAVIGATE study tests if the Enterra® Therapy System can reduce symptoms of chronic nausea and improve life quality in patients with normal gastric emptying. It involves using this system to see how it affects patients' conditions.

How Is the Trial Designed?

Group I: ON Group Experimental Treatment 1 Intervention

Participants assigned to the ON treatment group will begin with specified device programming values at the randomization visit. Device programming values may be adjusted at follow-up study visits during the blinding period. At the conclusion of the 4-month visit, participants will have their devices programmed to individualized therapy as determined by the Investigator. Investigators may adjust programming values at additional follow-up study visits.

Group II: OFF Group Experimental Treatment 1 Intervention

Participants assigned to the OFF treatment group will begin with device programming values set to off at the randomization visit. These settings will continue until the 4-month visit. At the conclusion of the 4-month visit, participants will receive specified device programming values. Device programming values may be adjusted at follow-up study visits. At the conclusion of the 8-month visit, participants will have their devices programmed to individualized therapy as determined by the Investigator.

Enterra Therapy System is already approved in United States for the following indications:

Approved in United States as Enterra Therapy System for:

• Chronic, intractable nausea and vomiting associated with gastroparesis caused by diabetes or an unknown origin in patients aged 18 to 70 years

Who Is Running the Clinical Trial?

Enterra Medical, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Bright Research Partners

Industry Sponsor

Trials

18

Recruited

2,700+

Published Research Related to This Trial

Experimental drugs like NK-1 receptor antagonists and 5-HT1A receptor agonists show promise in effectively treating nausea and vomiting associated with cyclic vomiting syndrome, suggesting they target central mechanisms in the brain responsible for these symptoms.

P6 acustimulation is also highlighted as a potential treatment, indicating that both pharmacological and non-pharmacological approaches may be effective in managing nausea and vomiting triggered by various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Central mechanisms of vomiting. Miller, AD.[2007]

Nausea and vomiting in advanced cancer can often be controlled quickly by identifying the underlying causes and using appropriate antiemetic treatments, particularly ondansetron and dexamethasone.

For post-cisplatin emesis, the combination of ondansetron and dexamethasone is the most effective, while ondansetron alone is effective for vomiting caused by upper abdominal radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nausea and vomiting in patients with cancer. Lichter, I.[2019]

In a double-blind study of 20 patients undergoing bone marrow transplantation, ondansetron significantly reduced the incidence of nausea and vomiting during total body irradiation (TBI), with only 1 out of 10 patients experiencing emesis compared to 5 out of 10 in the placebo group.

The study found no significant adverse events associated with ondansetron, indicating it is a safe and effective antiemetic option for patients undergoing TBI as part of their conditioning regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a double blind placebo controlled study of ondansetron as an antiemetic during total body irradiation in patients undergoing bone marrow transplantation. Tiley, C., Powles, R., Catalano, J., et al.[2019]

Empiric therapy has been the standard approach for treating cyclic vomiting syndrome, with various antimigraine and antiemetic agents showing efficacy rates between 40% to 90% in uncontrolled trials over the last decade.

Patients with a family history of migraines are more likely to benefit from antimigraine treatments, and additional therapies such as antiemetic sedatives, neuroleptics, and gastrointestinal prokinetic agents may also help manage symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclic Vomiting Syndrome. Li, BU.[2020]

Approximately one third of patients receiving cisplatin-based chemotherapy still experience nausea and vomiting within the first 24 hours, indicating a need for improved management strategies.

For highly emetogenic chemotherapy, combining ondansetron with dexamethasone is more effective than using dexamethasone alone, while for moderately emetogenic regimens, standard antiemetics can achieve similar control, suggesting that ondansetron may be reserved for cases where standard treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic agents. Bleiberg, H.[2019]

Citations

1. enterramedical.com enterramedical.com/hcp/clinical-studies/long-term-10-year-outcomes-study4/

Long-term 10-year outcomes study 1 In a retrospective study of 50 patients, Enterra Therapy significantly improved primary endpoint of nausea and vomiting in 54% of patients by greater than 50% ...

2. fda.gov fda.gov/media/181644/download

H990014 - Enterra® Therapy System Nausea/vomiting continued to occur this ... Enterra has not provided effectiveness data for the Enterra INS device this reporting period.

3. enterramedical.com enterramedical.com/hcp/clinical-studies/washington-university-5-year-data/

Washington University 5-year Data Patients with gastroparesis treated with Enterra Therapy showed statisticaly significant improvements in GCSI Total Score and Nausea-Vomiting Subscores at both ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4515290/

Gastric Electrical Stimulation with the Enterra System In phase I, significant improvement in median vomiting frequency was found in the ON period in the combined (all patients) group, although the same measure in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11392156/

Clinical Outcomes of a Large, Prospective Series of Gastric ... Patients' overall satisfaction with gastroparesis symptom improvement was high: 87.1% of patients at 1 year and 79.7% at 5 years postoperatively were “satisfied ...

6. enterramedical.com enterramedical.com/enterra-therapy/

Enterra Therapy IMPORTANT SAFETY INFORMATION. Enterra Therapy for treatment of chronic, resistant to medication nausea and vomiting associated with gastroparesis caused by ...

7. fda.gov fda.gov/media/107304/download

Executive Summary -Enterra® Therapy System - H990014 At 12 months follow-up, a 67.8% reduction in median weekly vomiting frequency was reported (compared to baseline values). Patients also reported improvements in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4274014/

Gastric electrical stimulation with Enterra therapy improves ... During the unblinded ON period, there was a reduction in weekly vomiting frequency (WVF) from baseline (61.2%, P < 0.001). There was a non-significant reduction ...