Trial to Evaluate Efficacy+Safety of Revita DMR Treatment Paradigm 1 and Retreatment in Type 2 Diabetes Patients

Not Applicable

Not yet recruiting

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Device: Revita® DMR Treatment; Other: Sham procedure

• Registration Number: NCT06092476
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief Summary

The objective of this study is to evaluate feasibility, safety, and efficacy of endoscopic DMR Treatment Paradigm 1 (compared to sham) and to evaluate feasibility, safety, and efficacy of re-treatment with DMR at 24 weeks (compared to baseline and a single DMR procedure) in patients with type 2 diabetes with non-insulin glucose lowering medications.

Detailed Description

The objective of this study is to evaluate feasibility, safety, and efficacy of endoscopic DMR Treatment Paradigm 1 (compared to sham) and to evaluate feasibility, safety, and efficacy of re-treatment with DMR at 24 weeks (compared to baseline and a single DMR procedure) in patients with type 2 diabetes with non-insulin glucose lowering medications.

The aimed effect is an adequate or improved glucose regulation and a decrease of HbA1c. Secondary effects include improved cardiovascular, hepatic, and metabolic parameters.

Study Timeline

• Study First Submitted: 2023-09-22
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-18
• Last Update Submitted: 2023-10-18
• Study First Posted: 2023-10-23
• Last Update Posted: 2023-10-23
• Study Start: 2023-11-01
• Primary Completion: 2026-04-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Diagnosed with Type 2 Diabetes. 2. Age ≥ 18 to ≤ 75 years. 3. Insulin naïve patients who are on stable dose (maximally approved or tolerated dose) of 2 or more glucose lowering drugs, including metformin, sulphonylurea (SU), (sodium-glucose cotransporter-2) inhibitors (SGLT-2i), Glucagon-like peptide-1 receptor agonists (GLP-1RA) or dipeptidyl peptidase 4 inhibitor (DPP-4i) and/or, thiazolidinedionderivaten (TZD) for at least 12 weeks.

2. BMI ≥ 24 and ≤ 40 kg/m2 5. HbA1c of ≥ 58 mmol/mol (7.5%) and ≤ 86 mmol/mol (10.0%).

3. In case of prestudy SU use, an HbA1c of ≥ 53 mmol/mol (7.0%). 6. Signed and dated written informed consent in accordance with Good Clinical Practice (GCP) and local legislation.

Exclusion Criteria

1. Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15.0 mmol/L) after an overnight 8-hour fasting at the end of run-in and confirmed by a second measurement on the consecutive day. 2. Subjects on SUs who are either unable or unwilling to discontinue SUs during study period, or subjects who are using insulin. 3. Known case of absolute insulin deficiency as indicated by a fasting plasma C-peptide value of <0.6 ng/ml.

   4. Diagnosis of autoimmune diabetes/Type 1 diabetes mellitus, monogenic (neonatal or maturity onset diabetes of the young (MODY)) diabetes or Type 1 diabetes in adults/latent autoimmune diabetes of adults (LADA).

   5. History of more than 1 severe hypoglycemia episode or unawareness within past 6 months in which third party assistance was needed.

   6. Clinically significant valvular heart disease or severe aortic stenosis. 7. Acute coronary syndrome (non-ST wave elevated myocardial infarction (STEMI), STEMI and unstable angina pectoris), stroke or transient ischemic attack within the past 3 months.

   7. Indication of acute liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 x upper limit of normal (ULN).

   8. Presence of acute or chronic active hepatitis B or C (except if hepatitis C is cured) or cirrhosis; or hepatic decompensation during the last 6 months; or alcoholic or autoimmune chronic hepatitis.

   9. Impaired renal function, defined as estimated Glomerular Filtration rate (eGFR) < 45 ml/min/1.73m2 or end stage renal failure or on dialysis.

   10. Diagnosed with esophageal motility disorder or Glomerular Filtration rate (GERD) gr 3 or diagnosed during screening endoscopy.

   11. Known history of a structural or functional disorder of the stomach, e.g. active gastric ulcer, chronic gastritis, gastric varices, hiatal hernia, stomach cancer or any other disorder of the stomach.

   12. Previous GI surgery that could affect the ability to treat the duodenum such as patients who have had a Billroth 2, Roux-and-Y gastric bypass, gastric sleeve or other similar procedures.

   13. Known intestinal autoimmune disease, including Celiac disease, or pre-existing symptoms of lupus erythematosus, scleroderma, or other autoimmune connective tissue disorder, which affects the small intestine. 15. Patients with active helicobacter pylori infection. Patients may be enrolled if they had history of h-pylori infection and were successfully treated.

   14. History of active malignancy or partial remission from clinically significant malignancy within the past 5 years. With the exception of basal or squamous cell skin cancer or carcinoma in situ or those received curative treatment and in complete remission for 5 years or if subject confirmed as cancer free.

   15. Blood dyscrasias or any disorders causing hemolysis or unstable Red Blood Cells (sickle cell trait is allowed).

   16. Known case of severe peripheral vascular disease. 19. Clinically active systemic infection. 20. Known immunocompromised status, including individuals who have undergone organ transplantation, chemotherapy, or radiotherapy within the past 12 months, clinically significant leukopenia or positive for the human immunodeficiency virus (HIV), on potential immunosuppressants.

   17. Current treatment with systemic steroids or change in dosage of thyroid hormones within 6 weeks prior to consent or any other uncontrolled endocrine disorder.

   18. Use of anticoagulation therapy (such as warfarin, coumadin, Novel Oral AntiCoagulants (NOAC) or anti-platelet agents (such as thienopyridine) which cannot be discontinued for 5-7 days or 2 drug half-lives before the procedure; Acetylsalicylic acid does not need to be discontinued.

   19. Actively participating in weight loss program or using medications for weight loss 3 months prior to randomization.

   20. General contraindications to deep or conscious sedation or general anesthesia or high risk (e.g., American Society of Anesthesiologists Classification (ASA) 4 or higher) or contraindications to upper GI Endoscopy.

   21. Nursing or Pregnant women or women of child bearing potential who are unwilling to practice acceptable method of birth control.

   22. History of alcohol, legal or illegal drug and substance abuse. 27. Intake of an investigational drug in another trial within 30 days prior to consent or active participation in another clinical trial of an investigational drug or device.

   23. Any other clinical or mental condition which would jeopardize subject's safety or makes subject a poor candidate for clinical trial participation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
DMR procedure	Revita® DMR Treatment	Patients receive Revita® DMR Treatment Paradigm 1. After unblinding at 24 weeks, they receive retreatment.
Sham procedure	Sham procedure	Patients receive a sham procedure. After unblinding takes place at 24 weeks, patients receive a Revita® DMR Treatment Paradigm 1. 48 weeks after initial sham (= 24 weeks after first DMR) patients may receive retreatment, if they want to.

Primary Outcome Measures

Name	Time	Method
Feasibility endpoint 2	During procedure	Feasibility endpoint is evaluated during and after the procedure: - Procedure time, defined as time between catheter in and catheter out.
Efficacy endpoint 1	24 weeks post DMR/sham	Efficacy is evaluated at 24 weeks compared to baseline and sham: - Mean change in Fasting Plasma Glucose (FPG)/Flash Glucose Monitoring (FGM)
Safety endpoint	12 weeks post DMR and 12 weeks post retreatment with DMR	Safety endpoint is evaluated 12 weeks post DMR and 12 weeks post retreatment with DMR; - Number (percentage) of patients experienced device and procedure-related Serious Adverse Events (SAEs), Unanticipated Device Effects (UADEs), Serious Adverse Device Effects (SADEs), Suspected Unexpected Serious Adverse Reaction (SUSARs)
Feasibility endpoint 1	During procedure	Feasibility endpoint is evaluated during and after the procedure: - Number of ablations, whether a DMR was successful (\>3 ablations)
Efficacy endpoint 2	24 weeks post DMR/sham	Efficacy is evaluated at 24 weeks compared to baseline and sham: - Change in HbA1c

Secondary Outcome Measures

Name	Time	Method
Efficacy endpoint 2: mean Change in Time in Range (TIR)	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 2: mean Change in Time in Range
Efficacy endpoint 3: In patients with baseline abnormal Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) values, change in ALT, AST, GGT	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 3: In patients with baseline abnormal ALT, AST and GGT values, change in ALT, AST, GGT
Efficacy endpoint 4: Change in body weight	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 4: Change in body weight
Efficacy endpoint 9: Change in MRI-proton density fat fraction (MRI-PDFF)	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 9: Change in MRI-PDFF
Mechanistic: Change in Cystatin Value	Through study completion, an average of 1 or 1,5 years	Mechanistic: Change in Cystatin Value
Efficacy endpoint 5: Change in Fasting C-peptide	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 5: Change in Fasting C-peptide
Efficacy endpoint 7: Change in homeostasis model assessment for insulin resistance (HOMA-IR)	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 7: Change in HOMA-IR
Secondary safety endpoint	Through study completion, an average of 1 or 1,5 years	Secondary safety endpoint is evaluated during follow-up and compared to baseline and sham at week 24 and compared to baseline and 12 weeks after (re)-DMR for all patients: incidences and event rates of hypoglycemic events during complete study period
Efficacy endpoint 10: Achievement of HbA1c ≤ 53 mmol/mol (7.0%)	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 10: Achievement of HbA1c ≤ 53 mmol/mol (7.0%)
Mechanistic: Mean Changes in small intestinal biopsy gene expression	Week 12 after (re)DMR	Mechanistic: Mean Changes in small intestinal biopsy gene expression
Mechanistic: Mean Changes in small intestinal biopsy metabolomics/proteomics	Week 12 after (re)DMR	Mechanistic: Mean Changes in small intestinal biopsy metabolomics /proteomics
Mechanistic: Change in Plasma Citrulline	Through study completion, an average of 1 or 1,5 years	Mechanistic: Change in Plasma Citrulline
Efficacy endpoint 1: mean change in HbA1c	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 1: mean change in HbA1c
Efficacy endpoint 2: mean Change in Fasting Glucose	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 2: mean Change in Fasting Glucose
Efficacy endpoint 6: Change in FPG	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 6: Change in FPG
Efficacy endpoint 8: Change in Framingham Risk Score-Cardiovascular risk score (FRS-CVD)	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 8: Change in Framingham Risk Score-Cardiovascular risk score (FRS-CVD)
Efficacy endpoint 11: Change in food intake (amount of calories, fat, carbohydrates, proteins etc.) based on intake registration data	Through study completion, an average of 1 or 1,5 years	Efficacy endpoint 11: Change in food intake (amount of calories, fat, carbohydrates, proteins etc.) based on intake registration data
Mechanistic: Change in resection tissue findings in morphological features	Week 12 after (re)DMR	Mechanistic: Change in morphological features
Mechanistic: Change in resection tissue findings in functional level changes	Week 12 after (re)DMR	Mechanistic: Change in functional level changes
Mechanistic: Change in resection tissue findings in cellular level changes	Week 12 after (re)DMR	Mechanistic: Change in cellular level changes