Insulin dependent type 2 diabetes (T2D) Non-alcoholic Fatty Liver Disease (NAFLD) Insulin resistance Cardiovascular health
Conditions
Interventions
Duodenal mucosal resurfacing (DMR),
stop long-acting insulin therapy,
start GLP-1 agonist(liraglutide),
start lifestyle intensification (nutrition and lifestyle counseling)
Sponsors
Academic Medical Center (AMC)
Meibergdreef 9, 1105 AZ Amsterdam
The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. Diagnosed with Type 2 Diabetes 2. 28 -75 years of age 3. Treatment with long acting insulin ≤ 2 years 4. On daily long acting insulin dose ≤ 1 U/kg 5. BMI ≥ 24 and ≤ 40 kg/m2 6. HbA1c ≤ 8.0% (64 mmol/mol) 7. Fasting C-peptide ≥ 500 pmol/L (1.5 ng/ml) 8. Willing to comply with study requirements and able to understand and comply with informed consent
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 |
|---|---|
| The following secondary endpoints are evaluated to identify improvement in cardiovascular, metabolic and hepatic parameters: •HbA1c (at screening and at 3, 6, 12 months follow-up) •Change in HbA1c (at 3, 6,9, 12 months follow-up) •Achieving target HbA1c of 7.0% (53 mmol/mol) (at 3, 6, 9, 12 months follow-up) •FPG (baseline, 3, 6, 9 and 12 months follow-up) •Change in FPG (at 3, 6, 9 and 12 months follow-up) •Peak and AUC glucose in MMTT (at baseline and 6 months follow-up) •Gut hormones in MMTT (at baseline and 6 months follow-up) •Pancreatic hormones in MMTT (at baseline and 6 months follow-up) •Metabolic profile from MMTT (at baseline and 6 months follow-up) •HOMA IR (at baseline and 6 months follow-up) •Insulin sensitivity (at baseline and 6 months follow-up) •Beta cell function (at baseline and 6 months follow-up) •Liver fat fraction (at baseline and 6 months follow-up) •Cardiac function (at baseline and 6 months follow-up) •ALT and AST (at baseline, 3, 6 and 12 months follow-up) •Change in AST and ALT (at 3, 6 and 12 months follow-up) •Fibrosis-4 (FIB-4) score (at DMR and 3 months follow-up) •Change in FIB-4 score (at 3 months follow-up) •Urine microalbumin (at screening, baseline, 3, 6, 9 and 12 months follow-up) •Blood pressure (at baseline and 6 months follow-up) •DEXA body scan (at baseline and 6 months follow-up) | — |
Contacts
Public ContactP. Smeele
Outcome results
None listed