Revita DMR for Obesity

(REMAIN-1 Trial)

Recruiting at 19 trial locations

Overseen By Jim Moat

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Fractyl Health Inc.

Must be taking: Tirzepatide

Must not be taking: Hypoglycemics, Corticosteroids, Anticoagulants, others

Disqualifiers: Diabetes, Pancreatitis, Substance abuse, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Fractyl is evaluating Revita Duodenal Mucosal Resurfacing (DMR) in the REMAIN-1 pivotal study, which is designed to include two cohorts - an open label cohort referred to as REVEAL-1, and a randomized cohort, which includes both a midpoint analysis and a pivotal analysis. Patients who previously lost at least 15% of their body weight on a GLP-1 can qualify for the open label REVEAL-1 cohort. The data generated from the REVEAL-1 cohort will be used for open label reporting as the study progresses. The REMAIN-1 randomized cohort will enroll patients living with obesity and a body mass index ("BMI") between 30 and 45 kg/m2 who are not currently on a GLP-1 drug. Patients will be prescribed tirzepatide and titrated to achieve at least 15% total body weight loss, at which time tirzepatide will be discontinued and patients will be randomized to Revita versus sham at 2:1. Midpoint Analysis of Randomized Cohort: The midpoint analysis of the randomized cohort will be performed at three months of follow-up on approximately 45 patients, allowing us to assess and report on safety and efficacy signals that could be anticipated in the pivotal analysis. These patients are distinct from those included in the pivotal analysis. Pivotal Analysis of Randomized Cohort: The pivotal analysis of the randomized cohort will be performed on approximately 315 patients (distinct from those included in the midpoint analysis) and will evaluate safety and efficacy in the first co-primary endpoint, which is weight regain from the time of tirzepatide discontinuation in Revita DMR versus sham patients at six months, with a primary objective of demonstrating a benefit of Revita DMR versus sham for weight maintenance after GLP-1 discontinuation. The second co-primary endpoint evaluates a responder rate among the Revita DMR treated group at one year to demonstrate the durability of the Revita DMR procedure for weight maintenance after discontinuation of a GLP-1-based therapy. Secondary objectives will include evaluation of the effectiveness of the Revita DMR procedure on the change in blood glucose levels, cardiovascular disease ("CVD") risk factors, body composition and pre-diabetes status. All patients enrolled in the study will receive diet and lifestyle counseling.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like hypoglycemic agents, weight loss drugs, and some corticosteroids are restricted. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the Revita Duodenal Mucosal Resurfacing (DMR) treatment for obesity?

Research shows that Duodenal Mucosal Resurfacing (DMR) can improve blood sugar control and metabolic health in people with type 2 diabetes, which may suggest potential benefits for weight management. ^{1 2 3 4 5}

How is the Revita Duodenal Mucosal Resurfacing (DMR) treatment for obesity different from other treatments?

Revita Duodenal Mucosal Resurfacing (DMR) is unique because it is a non-surgical, endoscopic procedure that targets the lining of the duodenum (the first part of the small intestine) to help with weight loss, unlike traditional surgical options like gastric bypass or duodenal switch which involve more invasive alterations to the digestive system. ^{6 7 8 9 10}

Research Team

Shelby Sullivan, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Eligibility Criteria

The REMAIN-1 trial is for adults aged 21-70 with obesity (BMI ≥30 kg/m2) who have lost at least 15% of their body weight on tirzepatide. Participants must be able to walk and climb stairs, not have diabetes, and women must use reliable contraception or be postmenopausal. Those with a history of unsuccessful dieting can join.

Inclusion Criteria

I have given my written consent to participate in the study.

I have tried and failed to lose weight through dieting at least once.

I am between 21 and 70 years old.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Run-in

Participants undergo a tirzepatide run-in dose-escalation period to achieve at least 15% body weight loss

16-26 weeks

Visits 2-6 for dose escalation

Study Intervention

Participants receive either the Revita DMR or sham procedure after achieving the required weight loss

1 week

Visit 8 for intervention

Follow-up

Participants are monitored for safety and effectiveness after the study intervention

52 weeks

Treatment Details

Interventions

• Revita Duodenal Mucosal Resurfacing (DMR) (Procedure)
• Sham (Procedure)

Trial Overview This study tests Revita DMR's ability to maintain weight loss compared to a sham procedure in people who've already shed significant weight on tirzepatide. It involves an initial run-in period followed by random assignment (2:1 ratio) to either the DMR treatment or sham for 48 weeks.

Participant Groups

Group I: Training Experimental Treatment 1 Intervention

Sites will gain experience with the study protocol and the Revita DMR procedure in an open-label, single-arm treatment assignment for participants who previously achieved 15% weight loss using a GLP-1

Group II: Active Active Control 1 Intervention

Patients who have achieved \>15% weight loss from baseline will receive the Revita DMR Procedure

Group III: Sham Placebo Group 1 Intervention

Patients who have achieved \>15% weight loss from baseline will receive and endoscopic evaluation and will have a catheter introduced but the Revita DMR procedure will not be performed

Who Is Running the Clinical Trial?

Fractyl Health Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Findings from Research

Duodenal mucosal resurfacing (DMR) is a safe and feasible endoscopic procedure that significantly improves glycaemic control in patients with type 2 diabetes, with effects sustained for at least 12 months, regardless of weight loss.

In a study of 46 patients, DMR led to significant reductions in HbA1c, fasting plasma glucose, and insulin resistance, with 80% of patients completing the procedure and most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study. van Baar, ACG., Holleman, F., Crenier, L., et al.[2022]

In the INSPIRE trial, combining Duodenal Mucosal Resurfacing (DMR) with a GLP-1 receptor agonist led to significant improvements in cardiovascular health, including a 24% reduction in visceral fat and decreased levels of triglycerides, cholesterol, and urine microalbumin after 6 months.

This treatment approach allowed 69% of patients to eliminate insulin therapy while also reducing their 10-year cardiovascular risk score, indicating a potential for improved metabolic and cardiovascular outcomes in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events. Meiring, S., Busch, CBE., van Baar, ACG., et al.[2022]

Duodenal mucosal resurfacing (DMR) did not significantly increase insulin sensitivity in insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity, suggesting that its mechanism of action may not involve improving insulin sensitivity.

The study, which included 32 participants over a 6-month period, found no significant differences in insulin secretion or metabolic outcomes between the DMR and sham endoscopy groups, indicating that DMR's effects may be context-dependent, potentially requiring hyperglycemic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome. Kaur, V., Dimitriadis, GK., Pérez-Pevida, B., et al.[2022]

In a feasibility study of 16 insulin-treated patients with type 2 diabetes, combining duodenal mucosal resurfacing (DMR) with GLP-1 receptor agonist therapy and lifestyle counseling led to 69% of patients being able to discontinue insulin therapy while maintaining good blood sugar control at 6 months.

The study demonstrated significant improvements in various metabolic parameters, including insulin resistance and body weight, with most patients remaining off insulin for up to 18 months, indicating a promising approach for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study. van Baar, ACG., Meiring, S., Smeele, P., et al.[2022]

Duodenal mucosal resurfacing (DMR) is an innovative endoscopic procedure that has shown beneficial effects on glycemic control and liver metabolism in patients with non-insulin dependent type 2 diabetes (T2D).

The analysis of four studies indicated that these metabolic improvements were observed at both 3 and 6 months after the DMR procedure, highlighting its potential as an effective treatment option for managing T2D.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Effects of Endoscopic Duodenal Mucosal Resurfacing: a Systematic Review and Meta-analysis. de Oliveira, GHP., de Moura, DTH., Funari, MP., et al.[2021]

In a study involving 6 patients with gastric leaks after bariatric surgery, the use of coated self-expandable stents (CSES) effectively sealed the leaks in 5 out of 6 cases, demonstrating a promising treatment option for this complication.

The approach showed good results in terms of morbidity and survival, suggesting that CSES can be a safe and effective alternative for managing gastroesophageal junction leaks following procedures like sleeve gastrectomy and duodenal switch.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of gastric leaks with coated self-expanding stents after sleeve gastrectomy. Serra, C., Baltasar, A., Andreo, L., et al.[2019]

Duodenal switch conversion is an effective salvage procedure for patients who have not achieved sufficient weight loss or have regained weight after previous bariatric surgeries, showing statistically significant improvements in weight loss at 6, 12, and 24 months.

The procedure is considered safe, with a low overall complication rate of 18%, and no reported fatalities, indicating it has a favorable safety profile compared to other bariatric procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal Switch Conversion in Non-responders or Weight Recurrence Patients. Lind, R., Ghanem, OM., Ghanem, M., et al.[2022]

The duodenal-jejunal bypass sleeve, a new endoscopically delivered device for weight loss, was successfully placed in a 36-year-old morbidly obese patient without complications, marking its first use in the United States.

After 3 months, the patient lost 9.09 kg, indicating the device's potential efficacy for weight loss, with ongoing studies planned to further assess its safety and mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenal- jejunal bypass sleeve: a totally endoscopic device for the treatment of morbid obesity. Gersin, KS., Keller, JE., Stefanidis, D., et al.[2008]

The duodeno-ileal omega switch (DIOS) procedure is emerging as a promising malabsorptive option for patients undergoing revisionary bariatric surgery, particularly in cases with complex digestive changes.

In a case study of a 52-year-old male, a two-stage re-revision surgery using DIOS effectively reduced weight and improved satiety, suggesting its potential as a primary approach in similar revision surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fusion of duodeno-ileal omega switch and stomach pouch reconstruction as revisionary surgery for failed laparoscopic adjustable gastric banding and sleeved lesser curvature resection. Karcz, WK., Zhou, C., Małczak, P., et al.[2020]

In a study of 51 morbidly obese patients undergoing duodenal switch surgery, significant improvements in health-related quality of life (HRQL) were observed, with scores normalizing to population norms by 1 and 2 years post-surgery.

Paid work participation increased from 54.9% to 66.7% over two years after the surgery, indicating that duodenal switch not only aids in weight loss but also enhances the ability to engage in paid employment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and paid work participation after duodenal switch. Roger Andersen, J., Aasprang, A., Bergsholm, P., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events. [2022]

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

Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome. [2022]

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

Duodenal mucosal resurfacing combined with glucagon-like peptide-1 receptor agonism to discontinue insulin in type 2 diabetes: a feasibility study. [2022]

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

Metabolic Effects of Endoscopic Duodenal Mucosal Resurfacing: a Systematic Review and Meta-analysis. [2021]

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

Treatment of gastric leaks with coated self-expanding stents after sleeve gastrectomy. [2019]

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

Duodenal Switch Conversion in Non-responders or Weight Recurrence Patients. [2022]

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

Duodenal- jejunal bypass sleeve: a totally endoscopic device for the treatment of morbid obesity. [2008]

9. Poland pubmed.ncbi.nlm.nih.gov

Fusion of duodeno-ileal omega switch and stomach pouch reconstruction as revisionary surgery for failed laparoscopic adjustable gastric banding and sleeved lesser curvature resection. [2020]

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

Health-related quality of life and paid work participation after duodenal switch. [2022]