EndoBarrier in Obese Subjects With Type 2 Diabetes Mellitus

EndoBarrierTM in Obese Subjects With Type 2 Diabetes: Impact on Pancreatic Function, Insulin Resistance, Gut Peptides and Gut Permeability - a Pilot Study

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02769728

Enrollment

Registered

2016-05-12

Start date

2016-02-29

Completion date

2019-01-31

Last updated

2024-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Type 2 Diabetes

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.

Interventions

DEVICEEndoBarrier

implantation of a duodeno-jejunal bypass liner for weight reduction in obese subjects with type 2 diabetes mellitus

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

no masking

Intervention model description

The endobarrier device was implanted and explanted under general anaesthesia by trained gastroenterologists.

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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)

Countries

Austria

Participant flow

Recruitment details

Participants were recruited at the University Hospital Graz (LKH-Univ. Klinikum Graz) between January 2016 and September 2016. The first participant was enrolled in February 2016 and the last participant was enrolled in October 2016.

Pre-assignment details

11 participants were screened. Due to 1 withdrawal of informed consent 10 participants were enrolled in the trial and got the endobarrier device implanted.

Participants by arm

Arm	Count
EndoBarrier EndoBarrier will be implemented for 9 months. EndoBarrier: implantation of a duodeno-jejunal bypass liner for weight reduction in obese subjects with type 2 diabetes mellitus	10
Total	10

Baseline characteristics

Characteristic	EndoBarrier
Age, Continuous	48 years STANDARD_DEVIATION 9
BMI	43.3 kilograms divided by height in meters sq STANDARD_DEVIATION 5
Body weight	121.2 kilogram STANDARD_DEVIATION 18.5
Diabetes duration in years	7 years STANDARD_DEVIATION 6
diastolic blood pressure	88 millimeters of mercury STANDARD_DEVIATION 12
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Height	1.68 meter STANDARD_DEVIATION 0.1
Hip circumference	128 centimeter STANDARD_DEVIATION 9
Region of Enrollment Austria	10 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	4 Participants
systolic blood pressure	133 millimeters of mercury STANDARD_DEVIATION 19
Waist circumference	128 centimeter STANDARD_DEVIATION 12
Waist to hip ratio	1 Ratio STANDARD_DEVIATION 0.1

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 10
other Total, other adverse events	9 / 10
serious Total, serious adverse events	4 / 10

Outcome results

Primary

Changes in Insulin Sensitivity

insulin sensitivity: measured by mean glucose infusion rate (in a hyperinsulinaemic-euglycaemic clamp) (value at 9 months minus value at baseline)