Revita DMR for Obesity

(REMAIN-1 Trial)

Not currently recruiting at 31 trial locations

Overseen By Jim Moat

Age: 18+

Sex: Any

Trial Phase: Academic

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

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Revita Duodenal Mucosal Resurfacing (DMR) to help individuals maintain weight loss after stopping medications like GLP-1, a type of weight loss drug. The study includes two groups: an open-label group for participants who have already lost 15% of their body weight with GLP-1, and a randomized group for those not currently using GLP-1. Participants must have a BMI between 30 and 45 and should have previously lost significant weight with tirzepatide, a medication that aids weight loss. The trial aims to determine if Revita DMR can help maintain weight loss, improve blood sugar levels, and reduce heart disease risk. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on weight maintenance strategies.

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 prior data suggests that the Revita Duodenal Mucosal Resurfacing (DMR) procedure is safe for obesity treatment?

Research has shown that Revita Duodenal Mucosal Resurfacing (DMR) is generally safe. In one study, participants reported no serious side effects within 24 weeks after treatment. Another study found no intestinal bleeding or other major problems in 40 patients. These findings suggest that the DMR procedure is safe for those who undergo it. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Revita Duodenal Mucosal Resurfacing (DMR) for obesity because it offers a novel approach by targeting the gut directly. Unlike standard treatments such as lifestyle modifications or medications like GLP-1 receptor agonists, Revita DMR involves a minimally invasive endoscopic procedure that modifies the lining of the duodenum. This technique could potentially reset hormonal pathways related to metabolism and weight regulation. By directly altering the gut environment, it aims to achieve significant weight loss, possibly providing a more effective and long-lasting solution for obesity.

What evidence suggests that Revita DMR is effective for obesity?

Research has shown that Revita Duodenal Mucosal Resurfacing (DMR), which participants in this trial may receive, can help people lose weight and improve metabolism in a lasting way. In earlier studies, 90% of patients lost weight one month after undergoing the DMR procedure, and 84% maintained the weight loss. DMR also improved insulin sensitivity and other aspects of metabolic health for up to two years in people with type 2 diabetes. These results suggest that DMR can effectively maintain weight loss and enhance metabolic health even after discontinuing certain medications. ^{1 3 6 7 8}

Who Is on the Research Team?

Shelby Sullivan, MD

Principal Investigator

Dartmouth-Hitchcock Medical Center

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Revita Duodenal Mucosal Resurfacing (DMR)
• Sham

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06484114

Study Details | NCT06484114 | Evaluation of the Safety ... Evaluation of the Safety and Efficacy of Revita® DMR on Body Weight Maintenance in Subjects With Obesity Who Have Achieved at Least 15% Weight Loss on ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33597157/

Safety and efficacy of hydrothermal duodenal mucosal ... Conclusions: DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0168822722000067

Durable metabolic improvements 2 years after duodenal ... DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 ...

4. ir.fractyl.com ir.fractyl.com/news-releases/news-release-details/fractyl-health-presented-new-analysis-pooled-data-revitar

Fractyl Health Presented New Analysis from Pooled Data ... The results still show that 90% of patients lost weight at one-month post-procedure; 84% of these patients maintained their body weight loss ...

5. orlandohealth.com orlandohealth.com/clinical-trials-and-research/find-a-clinical-trial/w2415510-study-to-assess-the-efficacy-of-revita-duodenal

Study to Assess the Efficacy of Revita® Duodenal Mucosal ... Co-Primary To demonstrate that Revita DMR is superior to sham in percent change in body weight from baseline to week 24 and To demonstrate that a majority ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8761999/

Safety and efficacy of hydrothermal duodenal mucosal ... Results from REVITA-2 confirm that DMR has a favourable safety profile. No UADEs were reported through 24 weeks post treatment, and there ...

7. ir.fractyl.com ir.fractyl.com/news-releases/news-release-details/fractyl-health-announces-groundbreaking-data-remain-1-midpoint

Release Details The treatment difference we saw in this study, with Revita patients continuing to lose weight while sham patients rapidly regained weight, is ...

8. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.15533

A look at duodenal mucosal resurfacing: Rationale for ... First-in-human safety analyses in 40 patients reveal that the DMR procedure was well tolerated, with no instances of intestinal bleeding, ...