Diabetes Mellitus, Type 2, Noninsulin-Dependent Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes, Revita System, DMR
Brief summary
The purpose of this study is to demonstrate the efficacy and safety of the Fractyl duodenal mucosal resurfacing (DMR) Procedure using the Revita System compared to a sham procedure for the treatment of uncontrolled type 2 diabetes. Subjects randomized to the DMR procedure are followed per protocol for 48 Weeks. The Sham treatment arm will cross over to receive the DMR treatment at 24 weeks with background medications held constant from 24-48 weeks of follow up.
Detailed description
The study is a multi-center, randomized, prospective, double-blinded (subject and endocrinologist) trial of type 2 diabetes patients sub-optimally controlled on 1 or more oral anti-diabetic medications comparing the Fractyl DMR procedure to sham procedure. Randomization will be 1:1 DMR treatment to sham. All subjects will participate in a 4 week oral anti-diabetic medication run-in period before the index procedure to confirm lack of blood glucose control in conjunction with medication compliance and nutritional counseling. The Sham treatment arm will cross-over to receive the DMR treatment at 24 weeks with background medications held constant 24weeks of follow up after the cross-over DMR procedure. The DMR treatment arm will be managed according to current diabetes standard of care. Subjects randomized to the DMR procedure are followed per protocol for 48 Weeks. The Sham treatment arm will cross over to receive the DMR treatment at 24 weeks with background medications held constant from 24-48 weeks of follow up.
Interventions
PROCEDUREDMR Procedure
The DMR procedure consists of hydrothermal ablation of the duodenum using the Revita System
PROCEDURESham Procedure
The sham procedure consists of placing the Revita Catheter into the stomach for 30 minutes and then removing it from the patient.
Sponsors
Fractyl Health Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
28 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 28-75 years of age 2. Diagnosed with Type 2 Diabetes and evidence of preserved insulin secretion. Fasting insulin \> 7 μU/ mL. 3. Glycated Hemoglobin (HbA1c) of 7.5 - 10.0% (59-86 mmol/mol) 4. Body Mass Index (BMI) ≥ 24 and ≤ 40 kg/m2 5. Currently taking one or more oral glucose lowering medications of which one must be Metformin, with no changes in dose or medication in the previous 12 Weeks prior to study entry 6. Able to comply with study requirements and understand and sign the informed consent
Exclusion criteria
1. Diagnosed with Type 1 Diabetes or with a history of ketoacidosis 2. Current use of Insulin 3. Current use of Glucagon-like peptide-1 (GLP-1) analogues 4. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year) 5. Known autoimmune disease, as evidenced by a positive Anti- Glutamic Acid Decarboxylase (GAD) test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder 6. Active H. pylori infection (Participants with active H. pylori may continue with the screening process if they are treated via medication and re-testing verifies the condition has resolved.) 7. Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions 8. History of chronic or acute pancreatitis 9. Known active hepatitis or active liver disease 10. Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn's Disease and Celiac Disease 11. History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia 12. Use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure 13. Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure. Use of aspirin is allowed. 14. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase 15. Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) 16. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications 17. Persistent Anemia, defined as Hgb\<10 g/dl 18. Estimated Glomerular Filtration Rate (eGFR) or Modified of Diet in Renal Diseae (MDRD) \<30 ml/min/1.73m\^2 19. Active systemic infection 20. Active malignancy within the last 5 years 21. Not potential candidates for surgery or general anesthesia 22. Active illicit substance abuse or alcoholism 23. Participating in another ongoing clinical trial of an investigational drug or device 24. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | Baseline and 24 Weeks post-procedure | The primary efficacy endpoint is the change from baseline at 24 weeks in HbA1c, DMR vs Sham |
| Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | Baseline and 12 Weeks post-procedure | The absolute change from baseline at 12 weeks in MR-PDFF in patients with baseline MR-PDFF \> 5% , DMR vs Sham |
Countries
Belgium, Brazil, Italy, Netherlands, United Kingdom
Participant flow
Pre-assignment details
All subjects participated in a 4-week oral antidiabetic drug (OAD) run-in period before the index procedure to confirm lack of blood glucose control in conjunction with medication compliance and nutritional counseling. All subjects were managed according to current diabetes standard of care.
Participants by arm
| Arm | Count |
|---|---|
| DMR Procedure (Europe) Subjects randomized to the DMR procedure are unblinded at 24 weeks and followed for an additional 24 weeks.
DMR Procedure: The DMR procedure consists of hydrothermal ablation of the duodenum using the Revita System | 39 |
| Sham Procedure (Europe) Subjects are unblinded at 24 Weeks. Sham subjects to cross over to receive DMR treatment at 24 Weeks and followed up for additional 24 weeks.
Sham Procedure: The sham procedure consists of placing the Revita Catheter into the stomach for 30 minutes and then removing it from the patient. | 36 |
| DMR Procedure (Brazil) Subjects randomized to the DMR procedure are unblinded at 24 weeks and followed for an additional 24 weeks.
DMR Procedure: The DMR procedure consists of hydrothermal ablation of the duodenum using the Revita System | 17 |
| Sham Procedure (Brazil) Subjects are unblinded at 24 Weeks. Sham subjects to cross over to receive DMR treatment at 24 Weeks and followed up for additional 24 weeks.
Sham Procedure: The sham procedure consists of placing the Revita Catheter into the stomach for 30 minutes and then removing it from the patient. | 16 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First 24 Weeks | Physician Decision | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | DMR Procedure (Europe) | Sham Procedure (Europe) | DMR Procedure (Brazil) | Sham Procedure (Brazil) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 6 Participants | 1 Participants | 3 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 30 Participants | 16 Participants | 13 Participants | 86 Participants |
| Age, Continuous | 59 years | 56.5 years | 56 years | 57.6 years | 58 years |
| BMI (kg/m2) | 31.4 kg/m2 | 30.4 kg/m2 | 32.3 kg/m2 | 31.6 kg/m2 | 31.4 kg/m2 |
| Fasting Glucose | 191 mg/dL | 185 mg/dL | 190 mg/dL | 182 mg/dL | 187 mg/dL |
| HbA1c (%) | 8.1 % of glycosylated hemoglobin | 8.2 % of glycosylated hemoglobin | 8.6 % of glycosylated hemoglobin | 8.15 % of glycosylated hemoglobin | 8.26 % of glycosylated hemoglobin |
| MRI-PDFF (%) among subjects with baseline MRI-PDFF >5% | 16.46 % of liver fat | 16.11 % of liver fat | 16.45 % of liver fat | 16.98 % of liver fat | 16.5 % of liver fat |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Black | 0 Participants | 0 Participants | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race undisclosed | 13 Participants | 12 Participants | 0 Participants | 0 Participants | 25 Participants |
| Race/Ethnicity, Customized Race White | 25 Participants | 21 Participants | 12 Participants | 13 Participants | 71 Participants |
| Region of Enrollment Belgium | 9 participants | 7 participants | 0 participants | 0 participants | 16 participants |
| Region of Enrollment Brazil | 0 participants | 0 participants | 17 participants | 16 participants | 33 participants |
| Region of Enrollment Italy | 11 participants | 8 participants | 0 participants | 0 participants | 19 participants |
| Region of Enrollment Netherlands | 8 participants | 9 participants | 0 participants | 0 participants | 17 participants |
| Region of Enrollment United Kingdom | 11 participants | 12 participants | 0 participants | 0 participants | 23 participants |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 8 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Male | 30 Participants | 28 Participants | 9 Participants | 8 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 37 | 0 / 17 | 0 / 16 | 0 / 33 | 0 / 4 |
| other Total, other adverse events | 31 / 39 | 26 / 37 | 16 / 17 | 14 / 16 | 26 / 33 | 4 / 4 |
| serious Total, serious adverse events | 5 / 39 | 1 / 37 | 3 / 17 | 0 / 16 | 0 / 33 | 0 / 4 |
Outcome results
Primary
Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham
The absolute change from baseline at 12 weeks in MR-PDFF in patients with baseline MR-PDFF \> 5% , DMR vs Sham
Time frame: Baseline and 12 Weeks post-procedure
Population: mITT population; not all patients from participant flow were able to undergo a MRI-PDFF. All patients who had a MRI-PDFF performed are analyzed and represented below.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DMR Procedure (Europe) | Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | -5.4 percentage change from baseline |
| Sham Procedure (Europe) | Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | -2.24 percentage change from baseline |
| DMR Procedure (Brazil) | Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | -5.4 percentage change from baseline |
| Sham Procedure (Brazil) | Change From Baseline at 12 Weeks in MR-PDFF, DMR vs Sham | -6.07 percentage change from baseline |
Primary
Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham.
The primary efficacy endpoint is the change from baseline at 24 weeks in HbA1c, DMR vs Sham
Time frame: Baseline and 24 Weeks post-procedure
Population: mITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| DMR Procedure (Europe) | Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | -0.60 percentage change from baseline |
| Sham Procedure (Europe) | Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | -0.30 percentage change from baseline |
| DMR Procedure (Brazil) | Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | -1.85 percentage change from baseline |
| Sham Procedure (Brazil) | Change From Baseline at 24 Weeks in Hemoglobin A1c (HbA1c), DMR vs Sham. | -1.60 percentage change from baseline |