Endoscopic Therapy for Type 2 Diabetes

(ReCET Trial)

Recruiting at 44 trial locations

Overseen By Marie Steinbrink, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Endogenex, Inc.

Must be taking: Non-insulin glucose-lowering

Must not be taking: Insulin, Anticoagulants, Weight loss, NSAIDs

Disqualifiers: Type 1 diabetes, Autoimmune disease, GI surgery, 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: 13

Duration: 1 day

264 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if endoscopic intestinal re-cellularization, also known as Endoscopic Re-Cellularization Via Electroporation Therapy (ReCET), can safely and effectively help people with type 2 diabetes manage their blood sugar levels better. The study focuses on individuals whose diabetes isn't well-controlled with pills but who aren't using insulin. Participants may qualify if they've had type 2 diabetes for at least six months and are on 2 to 4 glucose-lowering medications without recent changes. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research in diabetes management.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you have been on stable doses of your non-insulin glucose-lowering medications for at least 12 weeks before the study. Some medications, like certain blood thinners and NSAIDs, must be stopped before the procedure.

What prior data suggests that endoscopic intestinal re-cellularization therapy is safe for individuals with type 2 diabetes?

Research has shown that the ReCET procedure, a treatment using a scope for type 2 diabetes, is generally safe. This method, which employs gentle electric pulses to heal cells in the small intestine, is both safe and practical. When combined with the medication semaglutide, it appears to be a promising way to manage diabetes without serious side effects. Some studies suggest that this combination can help patients stop using insulin for up to 24 months. While these findings are encouraging, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for type 2 diabetes, which often involve medications like metformin or insulin injections that focus on managing blood sugar levels, Endoscopic Intestinal Re-Cellularization Therapy offers a completely different approach. This innovative technique uses an endoscopic procedure to rejuvenate and restore intestinal cells, potentially improving metabolic functions at their root. Researchers are excited about this method because it targets the gut, a key player in glucose metabolism, and may provide long-lasting benefits without the need for daily medication.

What evidence suggests that endoscopic intestinal re-cellularization therapy could be effective for type 2 diabetes?

Research has shown that endoscopic intestinal re-cellularization therapy, which participants in this trial may receive in the ReCET Arm, holds promise for people with type 2 diabetes. Studies found that many patients who underwent this procedure, along with the medication semaglutide, could stop using insulin while maintaining controlled blood sugar levels. Specifically, 86% of patients were off insulin after six months and maintained better blood sugar levels. This treatment uses a gentle electric pulse to refresh the lining of the intestine, aiding in blood sugar regulation. These early results suggest this therapy could be a safe and effective way to manage type 2 diabetes. ^{1 3 4 6 7}

Who Is on the Research Team?

Lian Cunningham, MD, PhD

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults aged 22-70 with type 2 diabetes, who have been stable on 2-4 non-insulin glucose-lowering meds. They should have an HbA1C of 7.5-10.5%, a BMI of 27-40 kg/m2, and no recent weight changes or severe diabetes complications like ketoacidosis. Participants must not be critically ill, pregnant, or have gastrointestinal diseases, liver issues, heart conditions, thyroid disorders, or use certain medications.

Inclusion Criteria

Agree not to donate blood during study participation

Willing and able to comply with study visits and tasks

I am taking 2-4 diabetes medications that do not include insulin, without recent changes.

Exclusion Criteria

Fasting serum C-peptide <1 ng/mL

I have had diabetic ketoacidosis or a severe diabetic coma before.

I have been diagnosed with type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either the ReCET therapy or a sham procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular visits over 12 months

Crossover

Participants in the sham arm may cross-over to receive the ReCET procedure

Post 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Endoscopic Intestinal Re-Cellularization Therapy

Trial Overview The study tests a new procedure called ReCET against a sham (fake) procedure to see if it can better control blood sugar in people with type II diabetes who don't take insulin. The safety and effectiveness will be compared between the two groups.

How Is the Trial Designed?

Group I: ReCET Arm Experimental Treatment 1 Intervention

Treatment Arm will receive the ReCET procedure.

Group II: Control Arm Placebo Group 1 Intervention

Control Arm will receive a sham procedure.

Endoscopic Intestinal Re-Cellularization Therapy is already approved in United States for the following indications:

Approved in United States as ReCET for:

• Type 2 Diabetes

Who Is Running the Clinical Trial?

Endogenex, Inc.

Lead Sponsor

Trials

3

Recruited

350+

Published Research Related to This Trial

In a 12-month study of 10 non-obese patients with type 2 diabetes, laparoscopic sleeve gastrectomy with duodenojejunal bypass led to significant reductions in fasting blood glucose and HbA1c levels, indicating improved diabetes control.

The procedure resulted in an average BMI reduction of 12.1%, although one patient experienced complications, highlighting the need for further research with larger groups to assess long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic sleeve gastrectomy with duodenojejunal bypass for the treatment of type 2 diabetes in non-obese patients: technique and preliminary results. Navarrete, SA., Leyba, JL., Llopis, SN.[2022]

Endoscopic therapies for obesity and type 2 diabetes (T2DM) are emerging as effective alternatives to surgery, potentially reaching more patients and alleviating the global burden of these conditions.

Recent innovations in small bowel endoscopic treatments, such as bypass liners and mucosal resurfacing, utilize mechanisms in the foregut and hindgut to promote weight loss and improve blood sugar control, although they are not yet FDA approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bariatric and Metabolic Therapies Targeting the Small Intestine. McCarty, TR., Thompson, CC.[2021]

In a study of 115 patients treated with endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia, lower platelet counts and albumin levels were associated with a higher risk of recurrence of precancerous lesions.

The findings suggest that monitoring platelet and albumin levels could help identify patients at greater risk for recurrence after ESD, potentially guiding follow-up care and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors in the treatment of gastric mucosal atypical hyperplasia by endoscopic submucosal dissection. Hong, Y., Chen, X., Li, G.[2022]

Barrett's esophagus, a precancerous condition, can potentially be reversed through a combination of acid control and endoscopic ablative therapies, which include various techniques like laser and electrocautery.

Endoscopic ablation offers a less invasive alternative to surgery for elderly patients or those with other health issues, but its long-term effectiveness and candidate selection criteria still need further validation before it can be considered a standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ablation of Barrett's mucosa. Sampliner, RE.[2013]

The study demonstrates that human fetal intestine contains insulin-producing cells that can be generated from Paneth/goblet cells through the ablation of FoxO1, suggesting a potential source for cell replacement in diabetes.

A combination treatment that blocks FOXO1, Notch, and TGF-β significantly improved the conversion of intestinal cells to insulin-producing cells in diabetic mice, leading to near-normal glucose levels, indicating a promising therapeutic strategy for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals. Du, W., Wang, J., Kuo, T., et al.[2023]

Encapsulated human islet transplantation offers a promising alternative to conventional insulin therapy for diabetes, potentially reversing the disease without the need for high-dose immunosuppression.

Future advancements may include using encapsulated porcine islets or proliferated human islets to address the shortage of donor tissues, making this therapy accessible to millions of diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulated islet cell therapy for the treatment of diabetes: intraperitoneal injection of islets. Soon-Shiong, P., Sandford, PA.[2011]

Stem cell therapy for diabetes mellitus (DM) aims to replace damaged pancreatic beta cells, with stem cells differentiating into functional cells after being introduced into the pancreas, highlighting a promising approach to treating this metabolic disorder.

Pancreas and islet transplants are effective treatments for insulin-dependent DM, and the use of bioresonance therapy with nosodes represents an innovative method, although the efficacy of this approach requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective Treatment of Diabetes Mellitus by Resonance Medicine. Jalan, S., Anjankar, A., Deshpande, S.[2022]

Cells from the antral stomach can be reprogrammed to become functional insulin-secreting cells, showing a surprising similarity to pancreatic β cells, which could provide a new source of insulin-producing cells for diabetes treatment.

In diabetic mouse models, these reprogrammed insulin(+) cells effectively suppressed hyperglycemia for at least 6 months and demonstrated rapid regeneration, indicating their potential for long-term glycemic control and use in bioengineered tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprogrammed Stomach Tissue as a Renewable Source of Functional β Cells for Blood Glucose Regulation. Ariyachet, C., Tovaglieri, A., Xiang, G., et al.[2022]

The gut epithelium is a promising target for diabetes treatment due to its large surface area, stem cell population, and ability to tolerate immune responses, making it suitable for developing insulin-producing cells.

Research shows that modifying gut cells to produce insulin or using genetically engineered enteroendocrine cells can effectively create insulin factories, offering a potential safe and personalized approach to diabetes therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering the gut for insulin replacement to treat diabetes. Mojibian, M., Glavas, MM., Kieffer, TJ.[2018]

Endoscopic therapies targeting the small bowel have emerged as effective treatments for obesity and type 2 diabetes, leveraging insights from surgical methods.

Innovations like endoluminal sleeves and dual-path enteral bypass are replicating the benefits of surgical bypass, while duodenal mucosal resurfacing shows promise for long-term diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small Bowel Target Devices and Techniques. Edmundowicz, SA.[2017]

In a study of 4114 Barrett's esophagus patients undergoing endoscopic eradication therapy (EET), the overall incidence of esophageal adenocarcinoma (EAC) was low at 6.01 per 1000 person-years, particularly among patients with high-grade dysplasia (HGD) where it was 12.9 per 1000 person-years.

The study also found that the all-cause mortality rate was 13.23 per 1000 person-years, with the highest rates in patients already diagnosed with EAC (25.1 per 1000 person-years), and the need for esophagectomy was less than 1% across all dysplasia grades, indicating a favorable safety profile for EET in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Esophageal Adenocarcinoma, Mortality, and Esophagectomy in Barrett's Esophagus Patients Undergoing Endoscopic Eradication Therapy. Smith, ZL., Thorgerson, AM., Dawson, AZ., et al.[2023]

Endoscopic resection using multiple ligation-assisted techniques (EMR-MLUS) is a safe and effective method for removing small rectal neuroendocrine tumors (R-NETs) ≤10 mm, with a high pathological complete resection rate of 94.74%.

While EMR-MLUS had a longer procedure time compared to ligation-assisted endoscopic submucosal resection (EMR-LUS), both methods showed high rates of endoscopic complete resection and no cases of recurrence or metastasis were reported in the follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple ligation-assisted endoscopic submucosal resection combined with endoscopic ultrasonography: a novel method to treat rectal neuroendocrine tumors. Xie, J., Hong, D., Li, D., et al.[2023]

The incisionless magnetic anastomosis system (IMAS) successfully created a partial jejunal diversion in all 10 patients with obesity and type 2 diabetes, with no serious adverse events reported, indicating a safe and feasible approach.

Patients experienced an average weight loss of 14.6% and significant reductions in glycated hemoglobin levels, suggesting effective management of diabetes and obesity without the need for intensive lifestyle changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial jejunal diversion using an incisionless magnetic anastomosis system: 1-year interim results in patients with obesity and diabetes. Machytka, E., Bužga, M., Zonca, P., et al.[2022]

In a study of 52 patients with type 1 gastric carcinoid, antrectomy was found to significantly reduce the need for follow-up procedures compared to polypectomy and EGD surveillance, with an average of 0.395 EGDs needed per year for antrectomy versus 1.038 for polypectomy.

Patients who underwent antrectomy had a lower risk of cancer recurrence (11%) compared to those who had polypectomy (44%), indicating that antrectomy may be a more effective treatment option for T1GC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic antrectomy: a safe and definitive treatment in managing type 1 gastric carcinoids. Jenny, HE., Ogando, PA., Fujitani, K., et al.[2016]

Endoscopic bariatric therapy offers a less invasive option for weight loss compared to traditional bariatric surgery, resulting in fewer complications while still achieving better weight loss outcomes than lifestyle changes or medications.

These therapies are significant advancements in obesity treatment, particularly for patients who may not be candidates for surgery, and include FDA-approved devices and those undergoing pivotal trials in the US.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic Management. Bennett, MC., Badillo, R., Sullivan, S.[2018]

Citations

1. mayoclinic.org mayoclinic.org/medical-professionals/digestive-diseases/news/researchers-study-novel-endoscopic-therapy-for-type-2-diabetes/mqc-20563134

Researchers study novel endoscopic therapy for type 2 ... This nonthermal procedure involves delivering a pulsed electric field (PEF) to facilitate the re-cellularization of the duodenum with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949708625000391

Durable insulin elimination after duodenal re ... These results suggest that duodenal ReCET combined with semaglutide is durable allowing insulin elimination up to 24 months and appears safe.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06267391

Study Details | NCT06267391 | Safety and Effectiveness of ... This study is designed to evaluate the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (T2D) ...

4. giejournal.org giejournal.org/article/S0016-5107(23)01630-9/abstract

RE-CELLULARIZATION VIA ELECTROPORATION ... These results suggest that the ReCET procedure is safe and feasible. ReCET in combination with semaglutide is a promising new therapeutic option that may ...

5. ddw.digitellinc.com ddw.digitellinc.com/p/s/re-cellularization-via-electroporation-therapy-recet-combined-with-glp-1ra-to-replace-insulin-therapy-in-patients-with-type-2-diabetes-6-months-results-of-the-eminent-study-3665

RE-CELLULARIZATION VIA ELECTROPORATION THERAPY ... At 6 months, 12 (86%) patients were off insulin, yet showed a significant improvement in glycemic control (HbA1c, fasting plasma glucose, time in range of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06267391

Study Details | NCT06267391 | Safety and Effectiveness of ... This study is designed to evaluate the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (T2D) ...

7. uclahealth.org uclahealth.org/clinical-trials/safety-and-effectiveness-endoscopic-intestinal-re

Safety and Effectiveness of Endoscopic Intestinal Re ... This study is designed to evaluate the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (T2D)