ESG + GLP-1RA for Obesity and Liver Fibrosis

Overseen By Michele Ryan, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Pichamol Jirapinyo, MD, MPH

Must not be taking: Anticoagulants, GLP-1RAs, SGLT2 inhibitors

Disqualifiers: Cirrhosis, Alcohol, Smoking, Malignancy, others

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

Compensation: Varies

Number of Visits: 13

Duration: 12 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally. While weight loss through lifestyle modification is the standard treatment, most patients regain weight limiting ultimate improvement in liver disease. On the other end of the spectrum, bariatric surgery has shown promise in the treatment of MASLD/metabolic dysfunction-associated steatohepatitis (MASH) due to its efficacy in inducing weight loss. Nevertheless, its adoption has been hindered by the perceived invasiveness of surgery. Over the past decade, endoscopic sleeve gastroplasty (ESG) has gained recognition as a promising minimally-invasive approach to weight loss. The procedure involves utilizing a Food and Drug Administration (FDA)-authorized endoscopic suturing device to reduce the gastric volume by 70%. Studies reveal that ESG is associated with approximately 18.2% weight loss at one year after the procedure, with sustained results for at least 10 years. Nevertheless, the effect of ESG on MASH remains unknown. In this study, the investigators will compare ESG + lifestyle modification versus lifestyle modification alone in treating histologic MASH. The study will randomize patients to one of two different treatment options: ESG + lifestyle modification or lifestyle modification alone.

Will I have to stop taking my current medications?

If you are currently taking an anticoagulant, anti-platelet medication, GLP-1RA, or SGLT2 inhibitor, you will need to stop these medications to participate in the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the treatment Endoscopic Sleeve Gastroplasty (ESG) combined with GLP-1RA for obesity and liver fibrosis?

Research shows that Endoscopic Sleeve Gastroplasty (ESG) is effective for weight loss and improving conditions related to obesity, like non-alcoholic fatty liver disease (NAFLD). Additionally, combining ESG with liraglutide, a type of GLP-1RA (a drug that helps control blood sugar and appetite), may enhance weight loss further. ^{1 2 3 4 5}

Is endoscopic sleeve gastroplasty (ESG) safe for humans?

Endoscopic sleeve gastroplasty (ESG) has been shown to be a safe procedure for weight loss in several studies, with no major complications reported. It is a less invasive alternative to traditional bariatric surgery, reducing the stomach size without incisions. ^{6 7 8 9 10}

How does the treatment ESG + GLP-1RA for obesity and liver fibrosis differ from other treatments?

This treatment combines Endoscopic Sleeve Gastroplasty (ESG), a minimally invasive procedure that reduces stomach size to aid weight loss, with GLP-1 receptor agonists, drugs that help control blood sugar and may improve liver health. This combination targets both obesity and liver fibrosis, offering a dual approach that is unique compared to treatments focusing on just one of these conditions. ^{2 3 11 12 13}

Research Team

Pichamol Jirapinyo, MD, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults aged 21-65 with obesity (BMI between 30 and 40), liver fibrosis, and NAFLD who have tried non-surgical weight-loss methods without success. Participants must be willing to follow a strict diet, attend regular follow-ups, complete tests, and live near the investigator's office. Women of childbearing age should agree to use birth control.

Inclusion Criteria

Your body mass index (BMI) is between 30 and 40.

I am between 21 and 65 years old.

I live close enough to the doctor's office to attend all my appointments.

Exclusion Criteria

I am currently taking corticosteroids, immunosuppressants, or narcotics.

Patients unwilling to participate in an established medically-supervised diet and behavior modification program, with routine medical follow-up

Patients who are pregnant or breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo endoscopic sleeve gastroplasty (ESG) and lifestyle modification or lifestyle modification alone for 12 months

12 months

Regular visits throughout the 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1, 3, 6, 9, and 12 months

Treatment Details

Interventions

• Endoscopic Sleeve Gastroplasty (ESG)
• GLP1-RA

Trial Overview The study compares three treatments: ESG only, GLP-1RA (Semaglutide) only, or both combined in patients with obesity and advanced liver issues due to NAFLD. It aims to see if combining these FDA-approved treatments improves weight loss and liver health more than each treatment alone.

Participant Groups

Group I: ESG + lifestyle modification Experimental Treatment 2 Interventions

Endoscopic sleeve gastroplasty weight loss procedure with a lifestyle modification program for 12 months.

Group II: Lifestyle modification Active Control 1 Intervention

Lifestyle modification program for 12 months.

Endoscopic Sleeve Gastroplasty (ESG) is already approved in United States for the following indications:

Approved in United States as Endoscopic Sleeve Gastroplasty (ESG) for:

• Obesity in patients with a body mass index (BMI) 30-50 kg/m2

Who Is Running the Clinical Trial?

Pichamol Jirapinyo, MD, MPH

Lead Sponsor

Trials

2

Recruited

600+

Findings from Research

Endoscopic sleeve gastroplasty (ESG) resulted in a lower percentage of total body weight loss (17.57%) compared to laparoscopic sleeve gastrectomy (LSG) (29.28%) at 12 months, but it was associated with significantly lower morbidity and shorter hospital stays.

ESG demonstrated a mean length of stay of just 0.34 days, much shorter than LSG (3.09 days) and laparoscopic adjustable gastric banding (LAGB) (1.66 days), making it a safer and more convenient option for select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic Sleeve Gastroplasty, Laparoscopic Sleeve Gastrectomy, and Laparoscopic Band for Weight Loss: How Do They Compare? Novikov, AA., Afaneh, C., Saumoy, M., et al.[2019]

Endoscopic sleeve gastroplasty (ESG) was successfully performed on 10 patients in a Norwegian center, demonstrating its feasibility as a less invasive weight loss procedure compared to traditional bariatric surgery.

The procedure resulted in a mean total body weight loss of 12.2% at 26 weeks and 9.1% at 52 weeks, with acceptable safety, although one patient experienced a minor complication that was managed without further issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of implementation of endoscopic sleeve gastroplasty (ESG) in Norway. Tønnesen, CJ., Hjelmesæth, J., Aabakken, L., et al.[2023]

Endoscopic sleeve gastroplasty (ESG) is an effective and safe procedure for weight loss, achieving an average total weight loss of 16.3% at 12 months, which is significantly greater than that from intragastric balloon insertion and high-intensity diet therapy.

ESG has a lower rate of adverse events (5.2%) compared to laparoscopic sleeve gastrectomy (16.9%) and intragastric balloon placement (17%), making it a safer option for obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and safety of endoscopic sleeve gastroplasty for treating obesity - a systematic review. Due-Petersson, R., Poulsen, IM., Hedbäck, N., et al.[2021]

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure for obesity, showing significant weight loss results with a mean BMI reduction of 9.3 kg/m2 at 6 months and sustained excess body weight loss of 35.6% at 6 months post-procedure.

The study involved 91 patients across six centers, demonstrating that ESG can be successfully implemented in new endobariatric programs, with a mean procedure duration of 85.1 minutes and a short hospital stay of about 27 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of endoscopic sleeve gastroplasty for obesity management in new bariatric endoscopy programs: a multicenter international study. Sarkar, A., Tawadros, A., Andalib, I., et al.[2022]

References

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

Endoscopic sleeve gastroplasty plus liraglutide versus endoscopic sleeve gastroplasty alone for weight loss. [2021]

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

Sleeve Gastroplasty Combined with the NLRP3 Inflammasome Inhibitor CY-09 Reduces Body Weight, Improves Insulin Resistance and Alleviates Hepatic Steatosis in Mouse Model. [2021]

3. India pubmed.ncbi.nlm.nih.gov

Endoscopic sleeve gastroplasty - minimally invasive treatment for non-alcoholic fatty liver disease and obesity. [2022]

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

Endoscopic Sleeve Gastroplasty, Laparoscopic Sleeve Gastrectomy, and Laparoscopic Band for Weight Loss: How Do They Compare? [2019]

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

Laparoscopic Sleeve Gastrectomy After Endoscopic Sleeve Gastroplasty: Technical Aspects and Short-Term Outcomes. [2021]

6. Australia pubmed.ncbi.nlm.nih.gov

Endoscopic sleeve gastroplasty using the novel single-channel suturing device: A multicenter experience. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Initial experience with endoscopic sleeve gastroplasty: technical success and reproducibility in the bariatric population. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A pilot study of implementation of endoscopic sleeve gastroplasty (ESG) in Norway. [2023]

9. Denmark pubmed.ncbi.nlm.nih.gov

Effect and safety of endoscopic sleeve gastroplasty for treating obesity - a systematic review. [2021]

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

Safety and efficacy of endoscopic sleeve gastroplasty for obesity management in new bariatric endoscopy programs: a multicenter international study. [2022]

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

Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty. [2021]

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

The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD. [2023]

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

Impact of Endoscopic Sleeve Gastroplasty in Non-alcoholic Fatty Liver Disease: a Systematic Review and Meta-analysis. [2023]