EndoBarrier in Obese Subjects With Type 2 Diabetes Mellitus

Not Applicable

Completed

Conditions: Obesity
Type 2 Diabetes

Interventions: Device: EndoBarrier

Registration Number: NCT02769728

Lead Sponsor: Medical University of Graz

Brief Summary: The aim of the study is to explore short and longer-term effects of the Endobarrier™ implantation on insulin resistance and beta-cell function assessed by repeated Botnia clamps. In addition changes in gut peptides and gut permeability after implantation of a removable duodeno-jejunal bypass device to induce diabetes remission in obese subjects with sub-optimally controlled type 2 diabetes mellitus will be determined. Further changes in body weight and body composition, the change in global cardiovascular risk from baseline to 12 months, estimated using the UKPDS risk engine will be recorded.

Detailed Description: Obesity and diabetes probably represent the most challenging threat to public health in the 21st century. Obesity has multiple deleterious effects on health, significantly increasing the risk of fatal and non-fatal diseases including type 2 diabetes (T2DM). Bariatric surgery is a well-established method for the treatment of morbid obesity and has increasingly been recognized as an effective, long-lasting treatment option for T2DM.

Recently a potential, non-invasive alternative to bariatric surgery, a duodenal-jejunal bypass liner (EndoBarrierTM) has been introduced. It is an endoscopically implantable and removable device that prevents contact between partially digested nutrients and the proximal intestine. This device was shown to reduce body weight and to improve glycaemic control in subjects with diabetes. Small pilot studies suggested a change in incretin levels, similar to that observed after gastric surgery with an improvement of insulin sensitivity and glucose metabolism. To better understand and characterize the hormonal and/or metabolic effects after the implantation and removal of the EndoBarrierTM, this monocentric, prospective, trial is being performed.

The primary objective of this study is to clarify the changes in gut peptides and gut permeability after implantation the EndoBarrierTM in obese subjects with sub-optimally controlled type 2 diabetes mellitus. Additionally, the investigators aim to determine the changes in body weight and measure of adiposity, the change in global cardiovascular risk from baseline to 12 months as well as the changes in insulin sensitivity and beta-cell function over time.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Participant is willing and able to give informed consent for participation in the study.
Type 2 diabetes
BMI 30-49 kg/m²
HbA1c ≥ 6.5% (48 mmol/mol)
Appropriate life style intervention measures have been tried but have failed to achieve or maintain adequate, clinically beneficial weight loss for at least 6 months
Person is generally fit for intervention
Person commits to the need for long-term follow-up

Exclusion Criteria

Type 1 diabetes mellitus
Maturity Onset Diabetes of the Young (MODY)
Secondary diabetes due to a specific disease or glucocorticoid therapy
Pregnancy or women of childbearing age without adequate contraception
Women who are breast-feeding
Hypothalamic cause of obesity, Cushing syndrome
Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
History of bariatric surgery or complex abdominal surgery
Inflammatory bowel disease
Pancreatitis
Cholelithiasis
Uncontrolled gastroesophageal reflux
Known upper GI bleeding conditions, e.g. gastric or esophageal varices
Congenital or acquired abnormalities of the upper GI tract, e.g. stenosis
Subjects with or a history of coagulopathy, upper gastro-intestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasia
Chronic non-steroidal anti-inflammatory drug (NSAID) or aspirin treatment (Subjects unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during the implant period)
Previous GI surgery that could affect the ability to place the device or the function of the implant
GLP-1 receptor agonist therapy
Known ischaemic heart disease or heart failure
History of stroke
Active Helicobacter pylori (Note: Subjects may be enrolled if they had a prior history of Helicobacter Pylori and were successfully treated)
Iron deficiency and/or iron deficiency anemia
Subjects or Family history of a known diagnosis or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
Known malignancy or any other multimorbid patient condition or circumstance, which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol or would put the participant at an unjustified risk

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EndoBarrier	EndoBarrier	EndoBarrier will be implemented for 9 months.

Primary Outcome Measures

Name	Time	Method
Changes in Insulin Sensitivity	Baseline and 9 months	insulin sensitivity: measured by mean glucose infusion rate (in a hyperinsulinaemic-euglycaemic clamp) (value at 9 months minus value at baseline)

Secondary Outcome Measures

Name	Time	Method
Changes in Glucagon Like Peptide -1 Levels	Baseline and 9 months	Glucagon like peptide -1 levels measured before the Meal Tolerance Test (value at 9 months minus value at baseline)
Changes in Gut Permeability	Baseline and 9 months	Gut permeability measured by the Lactulose/Mannitol Test (value at 9 months minus value at baseline)
Changes in Weight	Baseline and 9 months	Dual-energy X-ray absorptiometry fat mass (value at 9 months minus value at baseline)
Changes in UKPDS Risk Score for Coronary Heart Disease	Baseline and 9 months	The UKPDS Risk Engine provides risk estimates and 95% confidence intervals, in individuals with type 2 diabetes not known to have heart disease, for non-fatal coronary heart disease These can be calculated for any given duration of type 2 diabetes based on current age, sex, ethnicity, smoking status, presence or absence of atrial fibrillation and levels of HbA1c, systolic blood pressure, total cholesterol and HDL cholesterol. Units on a scale: 10 year risk to suffer non-fatal coronary heart disease (in %) lower scores mean a better outcome (value at 9 months minus value at baseline)