RESET Liner for Type-2 Diabetes and Obesity

(STEP-1 Trial)

Overseen By Stephen J Linhares, BS

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Academic

Sponsor: Morphic Medical

Must be taking: Diabetes medications

Must not be taking: Corticosteroids, PPIs, NSAIDs, others

Disqualifiers: Liver disease, Type 1 diabetes, others

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

Compensation: Varies

Number of Visits: 9

Duration: 9 months

264 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new device called the RESET System, designed to improve blood sugar control in people with type 2 diabetes and obesity. Participants will receive either the RESET System (also known as the EndoBarrier Liner, a duodenal-jejunal bypass liner) or a placebo procedure, along with lifestyle and dietary counseling. The trial seeks individuals who have struggled to control their blood sugar despite using diabetes medications for at least three months. Eligible participants should have type 2 diabetes with blood sugar levels higher than ideal and a body mass index (BMI) of 30 or above. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for diabetes and obesity.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including systemic corticosteroids, proton pump inhibitors, drugs affecting GI motility, weight loss medications, NSAIDs, and some supplements known to increase bleeding risk. If you are currently taking any of these, you will need to stop before and during the trial.

What prior data suggests that the RESET System is safe for glycemic improvement in patients with Type 2 Diabetes and obesity?

Research has shown that the EndoBarrier Liner has been tested in people with type 2 diabetes and obesity. In earlier studies, most participants found the EndoBarrier Liner easy to handle. They typically experienced only minor side effects, such as nausea or stomach discomfort, which are common with treatments affecting the digestive system. Serious problems were rare. These results suggest that the EndoBarrier Liner is generally safe for managing type 2 diabetes and obesity.

Why are researchers excited about this trial?

Unlike traditional treatments for type 2 diabetes, which often involve medication or lifestyle changes to improve insulin sensitivity or reduce blood sugar levels, the EndoBarrier Liner offers a unique approach. This device is placed in the upper part of the intestine through an endoscopy, creating a physical barrier between food and the intestinal wall. By doing so, it modifies the way the body absorbs calories and nutrients, potentially leading to weight loss and improved blood sugar control. Researchers are excited about this treatment because it offers a non-surgical option that directly impacts the digestive process, which could be a game-changer for patients struggling to manage their diabetes with existing therapies.

What evidence suggests that the RESET System is effective for glycemic improvement in Type 2 Diabetes?

Research shows that the EndoBarrier Liner, which participants in this trial may receive, can help people with type 2 diabetes manage their blood sugar levels more effectively. Studies have found that users of the EndoBarrier Liner experienced a significant drop in HbA1c levels, a key measure of blood sugar control, compared to non-users. Additionally, users lost weight, which is crucial for managing type 2 diabetes. The device functions by creating a barrier in the intestine, reducing calorie absorption and improving insulin use. These findings suggest that the EndoBarrier Liner could benefit people with type 2 diabetes who struggle with traditional treatments. Meanwhile, participants in the sham arm will undergo an upper endoscopy but will not receive the EndoBarrier Liner.

Who Is on the Research Team?

Christopher Thompson, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 22-65 with type 2 diabetes, HbA1c levels between 7.5% and 10%, BMI between 30 and 50, but have been on other diabetes meds without adequate control including insulin. Women must use birth control to prevent pregnancy during the trial.

Inclusion Criteria

Are you currently taking at least two medications to manage your diabetes?

Have you been diagnosed with Type 2 diabetes?

Is your HbA1c (a measure of blood sugar control) between 7.5% and 10%?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the RESET System treatment or sham procedure along with moderate intensity lifestyle and dietary counseling

9 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Follow-up visits at 9 and 21 months

What Are the Treatments Tested in This Trial?

Interventions

• EndoBarrier Liner
• Sham

Trial Overview The RESET System's effectiveness in improving blood sugar levels in patients with poorly controlled type 2 diabetes and obesity is being tested against a sham (fake) procedure, alongside lifestyle and dietary counseling based on ADA standards.

How Is the Trial Designed?

Group I: RESET Experimental Treatment 1 Intervention

Patients in ARM 1, will receive an upper endoscopy and will be treated with the RESET Liner

Group II: Sham Placebo Group 1 Intervention

Patients in Arm 2 will receive an upper endoscopy, but will not be treated with the RESET Liner.

EndoBarrier Liner is already approved in European Union for the following indications:

Approved in European Union as EndoBarrier Liner for:

• Type 2 diabetes
• Obesity

Who Is Running the Clinical Trial?

Morphic Medical

Lead Sponsor

Trials

1

Recruited

260+

Morphic Medical Inc.

Lead Sponsor

Trials

16

Recruited

2,300+

Biostatistical Consulting, Inc.

Collaborator

Trials

3

Recruited

750+

Published Research Related to This Trial

The duodenal-jejunal bypass liner significantly improved glycemic control in patients with Type 2 diabetes, with HbA1c levels decreasing from 8.6% to 7.5% and fasting glucose levels dropping from 203.3 mg/dl to 155.1 mg/dl after one year of implantation.

Insulin sensitivity improved by over 50% just one week after the device was implanted, suggesting that the mechanism of action involves a reduction in hepatic glucose output, although some deterioration in these benefits was observed 26 weeks after the device was removed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of proximal gut exclusion from food on glucose homeostasis in patients with Type 2 diabetes. Cohen, R., le Roux, CW., Papamargaritis, D., et al.[2022]

In a study involving 29 patients treated with the duodenal-jejunal bypass liner (DJBL), the long-term effects on weight loss showed minimal change, with a median weight of 102.0 kg after 4 years, which was not significantly different from the baseline weight of 106.1 kg.

The study indicated that the initial weight reduction benefits of the DJBL diminished over time, as evidenced by a total weight loss of only 2.2% after 4 years, suggesting the need for larger studies to better understand the long-term efficacy of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the EndoBarrier Device: a 4-Year Follow-up of a Multicenter Randomized Clinical Trial. van Rijn, S., Roebroek, YGM., de Jonge, C., et al.[2022]

The duodenal-jejunal bypass liner (DJBL) was safely implanted in 39 out of 42 morbidly obese subjects, with no procedure-related complications reported over a 1-year follow-up period.

Participants who completed the study experienced an average weight loss of 22.1 kg (about 19.9% of their total body weight) and significant improvements in various cardiometabolic risk factors, including waist circumference, blood pressure, and blood glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss and metabolic improvement in morbidly obese subjects implanted for 1 year with an endoscopic duodenal-jejunal bypass liner. Escalona, A., Pimentel, F., Sharp, A., et al.[2022]

The study investigates the effects of the Endobarrier™ device on insulin sensitivity and beta-cell function in 10 obese patients with type 2 diabetes over a 36-week period, aiming to understand its impact on glycemic control.

By preventing contact between food and the upper gastrointestinal tract, the Endobarrier™ may lead to significant changes in gut microbiome and permeability, which could further influence diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Duodeno-Jejunal Bypass Liner (EndoBarrierTM) Implantation on Insulin Sensitivity in Patients with Type 2 Diabetes Mellitus (T2DM): A Study Protocol for a Pilot Trial. Tripolt, NJ., Aberer, F., Url, J., et al.[2020]

The EndoBarrier™ device, used in a study with 10 participants suffering from type 2 diabetes and obesity, led to significant weight loss and improved insulin sensitivity within just 4 weeks of implantation.

Even after the device was removed, participants still showed notable improvements in glucose metabolism 24 weeks later, indicating potential long-term benefits of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EndoBarrier™ Implantation Rapidly Improves Insulin Sensitivity in Obese Individuals with Type 2 Diabetes Mellitus. Obermayer, A., Tripolt, NJ., Aziz, F., et al.[2022]

The duodenal-jejunal bypass liner (DJBL) treatment significantly improved weight loss and metabolic parameters, such as HbA1c and fasting glucose, in patients with obesity and type 2 diabetes mellitus over a 12-month period, with 24 out of 28 patients completing at least 6 months of treatment.

The DJBL is a safe and effective minimally invasive option for patients who have not achieved sufficient results from dietary treatment alone, demonstrating sustained benefits even after dietary interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of 6 and 12 months Duodenal-Jejunal Bypass Liner Treatment on Obesity and Type 2 Diabetes: a Crossover Cohort Study. van Rijn, S., Betzel, B., de Jonge, C., et al.[2019]

The EndoBarrier Gastrointestinal Liner (DJBS) showed significant weight loss results, with an average reduction of 5.1 kg and 12.6% excess weight loss compared to diet modification in a meta-analysis of 5 randomized controlled trials involving 235 subjects.

While the DJBS did not significantly improve blood sugar levels in patients with type 2 diabetes, it was associated with manageable side effects like abdominal pain and nausea, and no deaths were reported, indicating a relatively safe profile for this less invasive obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the EndoBarrier Gastrointestinal Liner on obesity and type 2 diabetes: a systematic review and meta-analysis. Rohde, U., Hedbäck, N., Gluud, LL., et al.[2022]

Citations