Clinical trial NCT02769728: EndoBarrier in Obese Subjects With Type 2 Diabetes Mellitus
Official title: EndoBarrierTM in Obese Subjects With Type 2 Diabetes: Impact on Pancreatic Function, Insulin Resistance, Gut Peptides and Gut Permeability - a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Obesity
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The endobarrier device was implanted and explanted under general anaesthesia by trained gastroenterologists.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in Insulin Sensitivity
timeFrame: Baseline and 9 months
Secondary outcomes:
measure: Changes in Glucagon Like Peptide -1 Levels
timeFrame: Baseline and 9 months
measure: Changes in Gut Permeability
timeFrame: Baseline and 9 months
measure: Changes in Weight
timeFrame: Baseline and 9 months
measure: Changes in UKPDS Risk Score for Coronary Heart Disease
timeFrame: Baseline and 9 months
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Dept. of Internal Medicine, Medical University of Graz
Study officials:
affiliation: Medical University of Graz, Auenbruggerplatz 15
name: Harald Sourij, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tripolt NJ, Aberer F, Url J, Hogenauer C, Schreiber F, Eherer A, Sourij C, Obermayer AM, Stadlbauer V, Svehlikova E, Brunner M, Kojzar H, Pferschy PN, Pieber TR, Sourij H. Impact of Duodeno-Jejunal Bypass Liner (EndoBarrierTM) Implantation on Insulin Sensitivity in Patients with Type 2 Diabetes Mellitus (T2DM): A Study Protocol for a Pilot Trial. Diabetes Ther. 2019 Feb;10(1):299-309. doi: 10.1007/s13300-018-0540-z. Epub 2018 Dec 11.