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

Trial Summary

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 data supports the effectiveness of the treatment Enterra Therapy System for gastroparesis?

Research shows that the Enterra Therapy System, which uses gastric electrical stimulation (GES), can improve symptoms like nausea and vomiting in patients with gastroparesis, including those with diabetic gastroparesis, for up to 10 years. ^{1 2 3 4 5}

Is Enterra Therapy safe for humans?

Enterra Therapy, which involves gastric electrical stimulation, has been studied for treating gastroparesis and has shown to be generally safe in humans, although it requires surgical implantation. ^{1 2 3 4 5}

Is the Enterra™ Therapy System a promising treatment for gastroparesis?

The Enterra™ Therapy System is a promising treatment for gastroparesis because it offers a new way to help manage the symptoms of this condition. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this research study is to evaluate if different Enterra® device programming methods active during sleeping hours can maintain gastroparesis-related symptom relief and quality of life measures. Participants in this study with existing Enterra® devices will be randomly assigned to one of three programming methods that will be active during sleep. Participants will answer daily questions about their gastroparesis symptoms on an application with their phone/tablet. Participants will answer quality of life questionnaires about their gastroparesis symptoms at study visits. Participants will be involved in the study for up to six months after treatment assignment. Programming parameters in the study are within currently approved labeling.

Research Team

Abigail Stocker, MD

Principal Investigator

University of Louisville

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gastric electrical stimulation improves outcomes of patients with gastroparesis for up to 10 years. [2022]

2. England 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. [2012]

3. United States pubmed.ncbi.nlm.nih.gov

Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

An endoscopic wireless gastrostimulator (with video). [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Gastric neuromodulation with Enterra system for nausea and vomiting in patients with gastroparesis. [2022]

6. India 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. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. Germany pubmed.ncbi.nlm.nih.gov

Synchronization of administrations of chemotherapy and erythropoiesis-stimulating agents and frequency of associated healthcare visits. [2021]

10. France pubmed.ncbi.nlm.nih.gov

[QuiPO: who inject EPO?]. [2016]