Enterra Programming for Gastroparesis

(RESTING Trial)

Recruiting at 1 trial location

Overseen By Jason Hamann, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Enterra Medical, Inc.

Disqualifiers: Post-surgical gastroparesis, Pregnancy, Chemical dependency, 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: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if different programming methods for the Enterra® device, used during sleep, can continue to provide symptom relief and improve the quality of life for individuals with gastroparesis, a condition affecting stomach emptying. Participants with an existing Enterra® device will be randomly assigned to one of three programming methods to test symptom control. Ideal participants have stable gastroparesis symptoms and are already using the Enterra® Therapy System, a gastric electrical stimulation device. As an unphased trial, this study offers participants the chance to explore innovative programming methods that could enhance their quality of life.

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 you are on stable medical therapy for gastroparesis symptoms. This suggests you may need to continue your current medications.

What prior data suggests that these Enterra® device programming methods are safe for gastroparesis patients?

Research has shown that the Enterra Therapy System is generally safe for people with gastroparesis. In a study of 50 patients, 54% experienced a significant decrease in nausea and vomiting, indicating that the device is well-tolerated. Another study found that patients were very satisfied with the improvement in their symptoms. Even after five years, nearly 80% of patients remained happy with the results. Additionally, Enterra's gentle electrical stimulation of the stomach has proven safe during pregnancy, suggesting the treatment is safe for various groups. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores new ways to optimize the Enterra™ Therapy System for gastroparesis by adjusting its programming during sleep. Unlike the standard consistent setting, this trial tests whether varying stimulation levels during sleep, either in 6-hour or 8-hour cycles, can improve symptoms and patient outcomes. This approach could lead to more personalized therapy, potentially offering better relief during both waking and sleeping hours. By cycling through different stimulation patterns, it aims to enhance the effectiveness of the device without increasing the overall stimulation burden.

What evidence suggests that these Enterra® device programming methods are effective for gastroparesis?

Research has shown that the Enterra Therapy System can help manage gastroparesis. One study found that patients using Enterra Therapy experienced fewer episodes of vomiting and other symptoms after six weeks. Another study reported significant improvement in symptoms like nausea and vomiting after five years. Long-term data also revealed that more than half of the patients experienced over a 50% reduction in nausea and vomiting. This trial will compare different programming cycles of the Enterra Therapy System. Overall, Enterra Therapy shows promise in helping patients with hard-to-treat gastroparesis by reducing symptoms and improving quality of life. ^{1 2 4 6 7}

Who Is on the Research Team?

Abigail Stocker, MD

Principal Investigator

University of Louisville

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with gastroparesis who already have the Enterra™ Therapy System implanted and are on stable medical therapy. They should not have cognitive impairments, other GI diseases that explain symptoms, severe night-time nausea/vomiting, or an irregular sleep schedule. Pregnant individuals or those planning pregnancy during the study are excluded.

Inclusion Criteria

I am willing and able to follow all study rules and attend all appointments.

Stable gastroparesis symptoms, in the opinion of the investigator

On stable supplemental nutritional support during the month prior to enrollment

Exclusion Criteria

I often feel very nauseous or vomit at night.

Pregnancy, or subject that intends to become pregnant during participation in the study

I experience severe stomach emptying issues when I wake up.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to one of three Enterra® device programming methods active during sleep, with daily symptom tracking and quality of life assessments.

6 months

Regular study visits for quality of life assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enterra™ Therapy System

Trial Overview The study tests if different programming methods of the Enterra™ device during sleep can help maintain symptom relief and quality of life in people with gastroparesis. Participants will be randomly assigned to one of three programming methods and monitored for up to six months.

How Is the Trial Designed?

Group I: Arm 2 Sleep Cycle Experimental Treatment 1 Intervention

Device programming parameters participants have at enrollment will be used during waking hours. During sleeping hours, the Enterra® device will cycle through modified programming over the course of 8 hours. Each hour, the Enterra® device will deliver 45 minutes of reduced stimulation, followed by 15 minutes of waking hours stimulation. At the end of the 8-hour sleep cycle, the Enterra® device will return to waking hours programming.

Group II: Arm 1 Sleep Cycle Experimental Treatment 1 Intervention

Device programming parameters participants have at enrollment will be used during waking hours. During sleeping hours, the Enterra® device will cycle through modified programming over the course of 6 hours. Each hour, the Enterra® device will deliver 30 minutes of reduced stimulation, followed by 30 minutes of waking hours stimulation. At the end of the 6-hour sleep cycle, the Enterra® device will return to waking hours programming.

Group III: Control Sleep Cycle Active Control 1 Intervention

Baseline device programming parameters will be used during study participation. No modification to Enterra® device programming will be in effect during waking or sleeping hours.

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

Approved in United States as Enterra Therapy System for:

• Chronic, intractable (drug refractory) nausea and vomiting secondary to gastroparesis of diabetic or idiopathic etiology in patients aged 18 to 70 years

Who Is Running the Clinical Trial?

Enterra Medical, Inc.

Lead Sponsor

Trials

4

Recruited

300+

Published Research Related to This Trial

Only 24.8% of chronic kidney disease patients self-administered Erythropoiesis Stimulating Agents (ESAs), despite improvements in administration methods, indicating a need for better support and education for patients.

The cost of nurse-administered ESA injections was significantly higher than self-administration, highlighting the potential for cost savings if more patients could be encouraged to self-administer their treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[QuiPO: who inject EPO?]. Vigneau, C., Le Stum, S., Isnard-Bagnis, C., et al.[2016]

Gastric electrical stimulation (GES) therapy with the Enterra system significantly improved symptoms and reduced hospitalizations in 221 patients with severe gastroparesis over a mean follow-up of 56 months, demonstrating sustained efficacy for up to 10 years.

The therapy was well-tolerated, with a low rate of adverse events (7% of patients experienced infections at the device site), and led to weight gain and a reduction in medication use across all patient groups, particularly benefiting those with diabetic and postsurgical gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric electrical stimulation improves outcomes of patients with gastroparesis for up to 10 years. McCallum, RW., Lin, Z., Forster, J., et al.[2022]

Gastric electrical stimulation (GES) using high frequency-short pulses, known as Enterra® Therapy, effectively reduces nausea and vomiting in patients with gastroparesis, with a response rate of 50-70%.

The antiemetic effects of Enterra Therapy are believed to be mediated through mechanisms involving improved gastric accommodation, enhanced vagal activity, and activation of central neurons, although further studies are needed to fully understand these mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric neuromodulation with Enterra system for nausea and vomiting in patients with gastroparesis. Yin, J., Abell, TD., McCallum, RW., et al.[2022]

In a study involving 189 dialysis patients in India, CERA (continuous erythropoietin receptor activator) effectively increased hemoglobin levels by an average of 2.11 g/dL over 16 weeks, demonstrating its efficacy in treating anemia related to chronic kidney disease.

The treatment was well tolerated, with serious adverse events reported but deemed unrelated to CERA, indicating a favorable safety profile for this medication in the studied population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single arm, prospective, open label, multicentre study for evaluation of efficacy and safety of IV CERA for treatment of chronic renal anaemia in dialysis patients not currently treated with ESA. Nainan, GK., Pathak, VR., Dalal, SS., et al.[2018]

A systematic review of 27 studies involving 5410 adults with chronic kidney disease (CKD) found that Continuous Erythropoiesis Receptor Activator (CERA) has little or no significant effects on mortality, major cardiovascular events, or the need for blood transfusions compared to other erythropoiesis-stimulating agents (ESAs) like epoetin or darbepoetin.

The evidence regarding CERA's efficacy is of low certainty, indicating that while it may be a longer-acting option, it does not show clear advantages over existing treatments for improving patient-centered outcomes in adults with CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease. Saglimbene, VM., Palmer, SC., Ruospo, M., et al.[2022]

A new miniature wireless gastric electric stimulation (GES) device was successfully tested in a nonsurvival swine model, showing that it can be implanted endoscopically, which is less invasive than traditional surgical methods.

Stimulation with the wireless GES device resulted in more regular gastric slow waves and consistent amplitudes, indicating its potential effectiveness in treating refractory gastroparesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An endoscopic wireless gastrostimulator (with video). Deb, S., Tang, SJ., Abell, TL., et al.[2023]

In a study of 221 patients with gastroparesis treated with Enterra gastric electrical stimulation (GES) for at least one year, significant symptom relief was observed in diabetic gastroparesis, which was consistently linked to reductions in gastric retention.

For idiopathic gastroparesis, the relationship between symptom improvement and gastric retention reduction was inconclusive, while no association was found for post-surgical gastroparesis, indicating that the effectiveness of GES may vary based on the underlying cause of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is symptom relief associated with reduction in gastric retention after gastric electrical stimulation treatment in patients with gastroparesis? A sensitivity analysis with logistic regression models. Hou, Q., Lin, Z., Mayo, MS., et al.[2012]

In a study of 55 patients with diabetic gastroparesis, gastric electrical stimulation (GES) using the Enterra system significantly reduced weekly vomiting frequency by 57% after 6 weeks and 67.8% after 1 year, indicating its efficacy in managing symptoms.

Patients also experienced improvements in overall symptom scores, gastric emptying, quality of life, and reduced hospital days, demonstrating the therapy's positive impact on both subjective and objective health measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. McCallum, RW., Snape, W., Brody, F., et al.[2022]

In a study of 9,961 cancer patients receiving chemotherapy, darbepoetin alfa (DA) was found to have a higher synchronization rate with chemotherapy sessions (67%) compared to epoetin alfa (EA) (58%), indicating that DA can be administered more conveniently alongside chemotherapy.

Patients receiving DA had significantly fewer healthcare visits, with 2.3 fewer visits for ESA administration and 3.0 fewer total visits compared to those on EA, suggesting that DA may reduce the overall burden on patients and healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits. Hill, JW., Shreay, S., McGarvey, N., et al.[2021]

CERA, a long-acting erythropoiesis-stimulating agent, shows potential cost advantages in treating anemia related to chronic kidney disease, but the evidence is limited and mostly derived from conference abstracts rather than peer-reviewed studies.

Current literature lacks sufficient data to definitively assess the cost-effectiveness of CERA, highlighting the need for well-designed studies to evaluate its economic benefits while ensuring effective anemia management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of continuous erythropoietin receptor activator in anemia. Schmid, H.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20538073/

Gastric electrical stimulation with Enterra therapy improves ... Conclusions: In patients with intractable DGP, 6 weeks of GES therapy with Enterra significantly reduced vomiting and gastroparetic symptoms. Patients had ...

2. 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 ...

3. 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% ...

4. cghjournal.org cghjournal.org/article/S1542-3565(10)00545-8/fulltext

Gastric Electrical Stimulation With Enterra Therapy ... At 12 months, 70% of diabetic patients and 77% of idiopathic patients reported more than 50% improvement in median vomiting frequency. At 12 ...

5. enterramedical.com enterramedical.com/hcp/clinical-evidence/

Clinical evidence “Enterra Therapy does improve refractory nausea and vomiting in some patients with gastroparesis and may improve glycemic control, nutritional status, and ...

6. fda.gov fda.gov/media/181644/download

H990014 - Enterra® Therapy System Gastric electrical stimulation is safe during pregnancy and delivery: Results from a French cohort. Neurogastroenterol Motil. 2023;35. (10) ...

7. 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 ...