DMR for Type 2 Diabetes

(REVITALIZE 1 Trial)

Not currently recruiting at 70 trial locations

Overseen By David Ahn

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Fractyl Laboratories, Inc.

Must be taking: Glucose lowering agents

Must not be taking: Psychoactive drugs, Sympathomimetics, Corticosteroids, Anabolic steroids

Disqualifiers: Type 1 diabetes, Severe hypoglycemia, Autoimmune diseases, Chronic kidney disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Duodenal Mucosal Resurfacing (DMR) for individuals with Type 2 Diabetes who do not see enough improvement with their current medications. The trial aims to compare the effectiveness and safety of DMR against a sham procedure (a fake treatment used as a control) to evaluate its impact on blood sugar, liver, and heart health. Individuals with Type 2 Diabetes, who are on stable diabetes medications and have moderately high blood sugar, might be suitable candidates for this trial. Participants will receive either the DMR treatment or the sham treatment and will be monitored for nearly a year to assess outcomes. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for Type 2 Diabetes.

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

The trial does not specify if you need to stop your current medications. However, you must be on at least one glucose-lowering agent without changes for at least 12 weeks before screening. Some medications that interfere with glucose metabolism are prohibited.

What prior data suggests that the Revita® system is safe for patients with Type 2 Diabetes?

Research has shown that Duodenal Mucosal Resurfacing (DMR) is generally safe for people with Type 2 diabetes. One study found that DMR helps improve how the body converts food into energy, enhancing insulin use, which is crucial for blood sugar control. Another study demonstrated that these benefits can last up to two years after treatment. These findings suggest that DMR is well-tolerated, with no major safety concerns reported. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Duodenal Mucosal Resurfacing (DMR) is unique because it uses a novel technique called hydrothermal ablation to target the duodenal mucosa, which is a different approach compared to standard treatments like oral medications or insulin for managing type 2 diabetes. Most traditional treatments focus on regulating blood sugar levels through medications that influence insulin production or sensitivity. In contrast, DMR directly modifies the lining of the intestine to potentially improve metabolic control. Researchers are excited about DMR because it offers a non-drug-based intervention that could benefit patients with inadequately controlled type 2 diabetes, providing a new avenue for treatment that might improve outcomes for those not responding well to current therapies.

What evidence suggests that the Duodenal Mucosal Resurfacing (DMR) procedure is effective for Type 2 Diabetes?

Research has shown that Duodenal Mucosal Resurfacing (DMR), one of the treatments studied in this trial, offers promising effects for people with Type 2 Diabetes. Studies have found that DMR can safely help control blood sugar levels and improve insulin use. Patients have experienced long-lasting benefits, with improvements still visible two years after the procedure. These findings suggest that DMR could be a good option for those whose diabetes isn't well managed by medication alone. The treatment seems to help by targeting the duodenum, an important part of the digestive system that also helps regulate blood sugar. Participants in this trial may receive either the active DMR treatment or a sham procedure for comparison. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 21-70 with Type 2 Diabetes, using insulin and certain other diabetes medications, who have a BMI of >24 to ≤40 kg/m^2. Participants should not be pregnant or breastfeeding and must use reliable contraception. They cannot have stomach disorders, severe kidney disease, recent heart issues, uncontrolled thyroid conditions, or a history of significant alcohol/substance abuse.

Inclusion Criteria

My fasting blood sugar is between 180 and 270 mg/dL after not eating overnight and stopping my usual diabetes medication for 24-36 hours.

My HbA1c level is between 7.5% and 9.5% after a stable period.

Your weight is within a certain range based on your height.

Exclusion Criteria

I have had severe or repeated urinary or genital infections recently.

I have an autoimmune disease that affects my small intestine.

My thyroid is underactive or not well-controlled.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the DMR procedure or a sham procedure. The DMR involves hydrothermal ablation of the duodenal mucosa.

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on glycemic, hepatic, and cardiovascular endpoints.

48 weeks

Crossover Treatment (Sham group)

Participants in the Sham treatment arm are offered crossover to receive the DMR treatment.

48 weeks

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial is testing the Revita® System's Duodenal Mucosal Resurfacing (DMR) procedure against a sham (fake) procedure to see if it improves blood sugar control and heart health in those whose diabetes isn't well-managed by insulin alone. Participants will either receive DMR or the sham treatment and be monitored for up to 48 weeks.

How Is the Trial Designed?

Group I: Duodenal Mucosal Resurfacing (DMR) Active Control 1 Intervention

Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal muscosa in an upper endoscopic procedure in patients with inadequately controlled type 2 diabetes.

Group II: Duodenal Mucosal Resurfacing Sham (Sham) Placebo Group 1 Intervention

Duodenal Mucosal Resurfacing Sham (Sham) treatment will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with inadequately controlled type 2 diabetes.

Duodenal Mucosal Resurfacing (DMR) is already approved in European Union, United Kingdom for the following indications:

Approved in European Union as Revita for:

• Type 2 Diabetes

Approved in United Kingdom as Revita for:

• Type 2 Diabetes

Who Is Running the Clinical Trial?

Fractyl Laboratories, Inc.

Lead Sponsor

Trials

6

Recruited

570+

Fractyl Health Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Fractyl Health, Inc.

Lead Sponsor

Trials

2

Recruited

340+

Published Research Related to This Trial

In a study of 27,583 patients with rheumatoid arthritis (RA), seropositivity for RF and ACPA was linked to better effectiveness of non-TNF biologic DMARDs (bDMARDs), particularly rituximab (RTX) and abatacept (ABA), compared to TNF inhibitors (TNFis).

Patients who were seropositive had lower rates of drug discontinuation and higher remission rates with RTX and ABA, indicating that seropositivity may help guide treatment choices in RA for improved outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries. Courvoisier, DS., Chatzidionysiou, K., Mongin, D., et al.[2021]

A study involving 1,588 rheumatoid arthritis patients found that oral administration of medications is the most preferred treatment option, significantly influencing patient choices over other factors.

Patients strongly preferred DMARDs that do not require combination with methotrexate and are not administered every 1-2 weeks, suggesting that treatments aligning with these preferences could improve patient compliance and adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach. Alten, R., Krüger, K., Rellecke, J., et al.[2022]

Dimethyl fumarate (DMF) has shown significant efficacy in treating relapsing-remitting multiple sclerosis (RRMS), with a 44%-53% reduction in annualized relapse rates and a 71%-90% reduction in new MRI lesions based on two phase III trials.

While DMF is generally well-tolerated, with no increased risk of opportunistic infections, it can cause gastrointestinal symptoms and skin flushing, particularly at the start of treatment, necessitating regular safety monitoring of blood counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate for relapsing MS. Serra, A., Fox, RJ.[2020]

Early use of disease-modifying antirheumatic drugs (DMARDs) is recommended for all patients diagnosed with rheumatoid arthritis (RA), highlighting their importance in changing treatment strategies.

Understanding the common adverse reactions associated with DMARDs is crucial for safe treatment, necessitating regular monitoring of patients to manage potential side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[DMARDs (disease-modifying antirheumatic drugs)]. Tanaka, E., Yamanaka, H.[2013]

A significant number of rheumatoid arthritis (RA) patients remain difficult-to-treat (D2T) despite advancements in management, often due to factors like treatment non-adherence, comorbidities, and the presence of other diseases such as fibromyalgia.

The review highlights that D2T RA may involve various underlying immune mechanisms and genetic factors, suggesting that it is a complex syndrome with different causes for each patient, rather than a single condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms underlying DMARD inefficacy in difficult-to-treat rheumatoid arthritis: a narrative review with systematic literature search. Roodenrijs, NMT., Welsing, PMJ., van Roon, J., et al.[2022]

Combining two biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis treatment significantly increases the risk of serious adverse events (SAEs), with a rate of 14.9% in the combination group compared to 6.0% in the single therapy group, based on a meta-analysis of six studies involving 623 patients.

Patients receiving full doses of both bDMARDs showed a particularly high risk of serious infections (6.7% vs 0.6%) and a higher overall rate of SAEs (17.1% vs 6.2%), indicating that while combination therapy may be effective, it carries notable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of combination therapy with two bDMARDs in patients with rheumatoid arthritis: A systematic review and meta-analysis. Boleto, G., Kanagaratnam, L., Dramé, M., et al.[2020]

In a study involving 1,098 rheumatoid arthritis patients from the DREAM-RA registry, 14 adverse drug reactions (ADRs) were reported with higher cumulative incidences than those listed in the Summary of Product Characteristics (SmPC) for disease-modifying anti-rheumatic drugs (DMARDs).

Specifically, hydroxychloroquine and sulfasalazine had 5 ADRs classified as 'common' in this study, despite being labeled as having 'unknown' incidence in the SmPC, highlighting the importance of real-world data in understanding drug safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of real-world reported adverse drug reactions in rheumatoid arthritis patients. Giraud, EL., Jessurun, NT., van Hunsel, FPAM., et al.[2021]

Biosimilars of adalimumab, including FKB327, ABP 501, and others, have been shown to be highly similar to the reference product in terms of structure, efficacy, safety, and immunogenicity, making them effective alternatives for treating rheumatoid arthritis (RA).

Switching studies indicate that there are no significant changes in efficacy, safety, or immunogenicity when patients switch from the reference adalimumab to its biosimilars, supporting their use as cost-effective options for patients with limited access to biologic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Huizinga, TWJ., Torii, Y., Muniz, R.[2021]

In a 24-week phase 3 study involving 225 patients, including 142 East Asians, delayed-release dimethyl fumarate (DMF) significantly reduced the number of new gadolinium-enhancing lesions by 84% compared to placebo, demonstrating strong efficacy in treating relapsing-remitting multiple sclerosis (RRMS).

The safety profile of DMF was consistent across the study population, with flushing and gastrointestinal events noted as common side effects, indicating that DMF is a viable treatment option for East Asian patients with RRMS, similar to its effects in predominantly white populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries. Saida, T., Yamamura, T., Kondo, T., et al.[2022]

In a study of 578 rheumatoid arthritis patients treated with biological DMARDs, about 10% experienced radiographic progression, indicating new bone erosions after 12 months.

Factors such as younger age, high disease activity at baseline, absence of conventional DMARDs, and existing erosions were linked to a higher risk of developing new erosions, leading to a predictive model with good accuracy (AUC 0.846) for identifying at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with radiographic progression in rheumatoid arthritis starting biological diseases modifying anti-rheumatic drugs (bDMARDs). Adami, G., Fassio, A., Pistillo, F., et al.[2023]

In a study involving 170 patients with rheumatoid arthritis who had inadequate responses to conventional treatments, both tofacitinib and biological DMARDs showed similar improvements in disease activity and quality of life after 6 months, indicating comparable efficacy.

Both treatment groups experienced similar rates of adverse events, with no deaths reported, suggesting that tofacitinib is as safe as biological DMARDs for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in RA patients treated with tofacitinib or bDMARDs in real-life conditions in two Latin American countries. Reyes, JM., Gutierrez, MV., Madariaga, H., et al.[2023]

In a study of 1274 biologic-naïve rheumatoid arthritis patients with moderate disease activity, researchers identified seven distinct trajectories of disability scores over three years, indicating significant variability in patient outcomes based on baseline health status.

The findings suggest that patients with moderate disease activity but high disability scores may benefit from more aggressive treatment with biologic disease-modifying anti-rheumatic drugs (bDMARDs), as current guidelines typically exclude them from such therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity. Pan, Y., Norton, S., Gwinnutt, JM., et al.[2020]

A consensus among North American clinicians identified effective strategies for managing gastrointestinal adverse events (AEs) associated with delayed-release dimethyl fumarate (DMF) in multiple sclerosis patients.

Recommended management strategies include taking DMF with food, gradually increasing the dose, reducing the dose if necessary, and using symptomatic therapies to improve tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Management of Gastrointestinal Events Associated with Delayed-Release Dimethyl Fumarate: A Delphi Study. Theodore Phillips, J., Erwin, AA., Agrella, S., et al.[2022]

Dimethyl fumarate (DMFU) demonstrated protective effects against intestinal ischemia/reperfusion injury in Wistar rats, enhancing the expression of Nrf2 and its downstream target HO-1, which are crucial for cellular defense mechanisms.

DMFU also exhibited anti-inflammatory and anti-apoptotic properties by reducing inflammatory markers (like TNF-α and IL-1β) and increasing protective proteins (like Bcl-2), indicating its potential as a therapeutic agent for intestinal injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate protects against intestinal ischemia/reperfusion lesion: Participation of Nrf2/HO-1, GSK-3β and Wnt/β-catenin pathway. Gendy, A., Soubh, A., Al-Mokaddem, A., et al.[2021]

Dimethyl fumarate (DMF) significantly reduced the onset of type 1 diabetes in non-obese diabetic (NOD) mice, with a decrease from 54.2% to 25% in a spontaneous diabetes model and from 58.3% to 16.7% in an accelerated model, indicating its potential efficacy in delaying diabetes onset.

DMF treatment also lowered inflammation in the islets, as shown by a reduced insulitis score and decreased levels of various proinflammatory cytokines, suggesting that DMF protects β-cells from oxidative stress and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Autoimmune Diabetes in NOD Mice by Dimethyl Fumarate. Li, S., Vaziri, ND., Swentek, L., et al.[2021]

Citations

1. 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03653091

Safety & Effectiveness of Duodenal Mucosal Resurfacing ... The Revita™ System is being investigated to assess the ability to improve glycemic control in conjunction with diet and exercise in patients with Type 2 ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35032562/

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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02879383

Study Details | NCT02879383 | Effect of Duodenal Mucosal ... The purpose of this study is to demonstrate the efficacy and safety of the Fractyl duodenal mucosal resurfacing (DMR) Procedure using the Revita System ...

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

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

7. academic-med-surg.scholasticahq.com academic-med-surg.scholasticahq.com/article/145731-sustained-glycaemic-improvement-after-duodenal-mucosal-resurfacing-in-type-2-diabetes

Sustained Glycaemic Improvement After Duodenal Mucosal ... This case demonstrates that DMR may serve as a safe and beneficial adjunctive approach for individuals with treatment-resistant type 2 diabetes ...