Type 2 diabetes
Conditions
Interventions
Endoscopic Duodenal Mucosal Resurfacing (DMR) procedure, substitution of
insulin by a GLP-1 analogue (Liraglutide) with the additional support of
lifestyle counseling.
Diabetes
Efficacy
Treatment
Sponsors
Academisch Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. 28 -75 years of age 2. Treatment with long acting insulin * 5 years 3. On daily long acting insulin dose * 1 U/kg 4. BMI * 24 and * 40 kg/m2 5. HbA1c * 8.0% (64 mmol/mol) 6. Fasting C-peptide * 500 pmol/L (1.5 ng/ml) 7. Willing to comply with study requirements and able to understand and comply with informed consent 8. Signed informed consent form
Exclusion criteria
Exclusion criteria: 1. Diagnosed with Type 1 Diabetes or with a history of ketoacidosis 2. Fasting C-peptide < 500 pmol/L (1.5 ng/ml) 3. Current use of multiple daily doses insulin or insulin pump 4. Current use of a sulfonylurea derivate or meglitinide 5. Known autoimmune disease, as evidenced by a positive Anti-GAD test, including Celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder 6. 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 7. History of chronic or acute pancreatitis 8. Known active hepatitis or active liver disease 9. Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn*s Disease and Celiac Disease 10. History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia 11. Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 7 days before and 14 days after the procedure 12. 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. 13. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase 14. Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide) 15. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications 16. Persistent Anemia, defined as Hgb<10 g/dl 17. eGFR or MDRD <30 ml/min/1.73m^2 18. Active systemic infection 19. Active malignancy within the last 5 years 20. Not potential candidates for surgery or general anesthesia 21. Active illicit substance abuse or alcoholism 22. Participating in another ongoing clinical trial of an investigational drug or device 23. 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 |
|---|---|
| Protocol driven free of insulin at 6 months including and an HbA1c * 7.5%. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy endpoints at 3 (if applicable) and 6 months to identify improvement in cardiovascular, metabolic and hepatic parameters: a. HbA1c b. Change in HbA1c c. Achieving target HbA1c of 7% d. FPG e. Change in FPG f. Peak and AUC glucose in MMTT g. Gut hormones in MMTT h. Pancreatic hormones in MMTT i. Metabolic profile from MMTT j. HOMA IR k. Insulin sensitivity l. Beta cell function m. Liver fat fraction n. Cardiac function o. ALT and AST p. Change in AST and ALT q. Fibrosis-4 (FIB-4) score r. Change in FIB-4 score s. Urine microalbumin t. Blood pressure u. DEXA body scan The safety endpoint is the incidence rate of the following events at 6 months and 12 months post-procedure: a. All Procedure and device-related Serious Adverse Events (SAEs) and Unanticipated Adverse Device Effects (UADEs) b. All SAEs and UADEs c. Number of hypo-glycemic events (blood glucose level of | — |
Countries
The Netherlands
Outcome results
None listed