A Randomised Controlled Trial of a Duodenal Sleeve Bypass Device (EndoBarrier)Compared With Standard Medical Therapy for the Management of Obese Subjects With Type 2 Diabetes
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Imperial College London
- Enrollment
- 170
- Locations
- 2
- Primary Endpoint
- HbA1c reduced by 20%
Study Overview
Brief Summary
The management of obesity is challenging and obesity surgery is by far the most effective treatment currently available. Recent medical research indicates that it also improves the management of blood glucose levels in people with type 2 diabetes. Obesity surgery carries different risks and benefits and it is important to balance these by choosing the right procedure for each patient. Therefore new effective strategies to prevent and reduce obesity and its complications such as type 2 diabetes mellitus are needed. This study is designed to see whether a new device called the EndoBarrier Gastrointestinal Liner helps patients manage their blood sugar levels and lose weight. It is a randomised, placebo controlled trial which compares the potential of the EndoBarrier device with conventional drug therapy, diet and exercise for obesity related type 2 diabetes, and their effectiveness on metabolic state (HbA1c reduced by 20% and blood pressure below 135/85), weight loss, and quality of life. It will further evaluate whether any other conditions that may be related to obesity could become less severe and collect information about complications to determine the safety of the device. The study will also perform various measurements and tests to understand the underlying mechanism of the device. After an initial screening visit to determine patients eligibility, they will be invited for 14 subsequent visits. Patients will be randomised into either having the EndoBarrier device or standard medical therapy treatment for 12 months followed by another 12 months follow-up period. They will also be routinely seen by specialist dietitian who will provide dietetic support throughout the study.
Detailed Description
Patients will be recruited via primary care and secondary care trusts. After an initial screening visit to determine subject's eligibility, they will be randomised to either the EndoBarrier or Control arm (conventional medical therapy including dietary counselling), and invited for 15 study visits over 24 months. The standard medical therapy drug titrations will be carried out in accordance with the guidelines of the American Diabetes Association. These guidelines have been chosen as they are applicable to an International audience and thus would adhere to the current best worldwide practice that would still be likely to be relevant when the results of this trial are published following study completion.
Patients will receive the intervention for 12 months and then be followed up for 12 months. They will be contacted via telephone in between visits to monitor any problems and boost motivation.
The main outcome of this study is to compare the EndoBarrier device with conventional medical therapy, diet and exercise for obesity related type 2 diabetes and their effectiveness on:
- Metabolic state as defined by the International Diabetes Federation (IDF) with an HbA1c < 6% (or < 42 mmol/mol) and a blood pressure < 135/85mmHg
- Absolute weight loss.
Patients will also be invited to participate in one of 3 sub-groups as part of the mechanistic studies (Group 1: functional MRI (fMRI), Group 2: insulin clamps or Group 3: food preference). Participation in the sub-studies is optional.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18-65 years (male or female)
- •T2DM for at least 1 year (HbA1c 7.5-10.0% = 58-86 mmol/mol)
- •On oral T2DM medications (metformin is allowed, but not required)
- •BMI 30-50 kg/m2 with adequate insulin reserve as indicated with insulin C-peptide levels > 1665 pmol/L
Exclusion Criteria
- •Language barrier, mental incapacity, unwillingness or inability to understand and be able to complete questionnaires
- •Non-compliance with eligibility criteria
- •Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate or reliable contraceptive methods
- •Current use of insulin
- •Previous diagnosis with Type 1 DM or a history of ketoacidosis
- •Requirement of NSAIDs (non-steroidal anti-inflammatory drugs) or prescription of anticoagulation therapy during the implant period
- •History of iron deficiency and/or iron deficiency anaemia
- •Symptomatic gallstones or kidney stones at the time of screening
- •History of coagulopathy, upper gastro-intestinal bleeding conditions such as oesophageal or gastric varices, congenital or acquired intestinal telangiectasia
- •Previous GI surgery that could affect the ability to place the device or the function of the implant
- •History or presence of active H. pylori (if subjects are randomised into the EndoBarrier arm and have a history or presence of active H. pylori - tested during study visit 2 - they can receive appropriate treatment and then subsequently enrol into the study)
- •Family history of a known diagnosis or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
- •Severe liver (AST, ALT or gGT >4 times upper limit) or kidney failure (serum creatinine >180mmol/l), estimated Glomerular Filtration Rate (GFR) cut-off is 60
- •Severe depression, unstable emotional or psychological characteristics (indicated by Beck Depression Inventory II score >28)
- •Poor dentition and inability to adequately chew food
- •Planned holidays up to three months following the EndoBarrier Implant
- •Previous EndoBarrier implantation
- •Metal implant unsuitable for MRI scanning and claustrophobia as contraindications for MRI scans (sub-group 1 - fMRI study only)
- •Vegetarian, vegan, gluten or lactose intolerance as unsuitable for fMRI food picture paradigm (sub-group 1 - fMRI only)
Arms & Interventions
EndoBarrier Arm
The EndoBarrier Gastrointestinal Liner device received CE Mark for 12 months implant duration on 11 December 2009 and is a single use, minimally invasive device, used to achieve weight loss and improve Type 2 Diabetes status in subjects who are obese. The intent of the EndoBarrier Gastrointestinal Liner is to mimic portions of the standard Roux-en-Y bypass procedure. The device consists of 3 components: the implant, the delivery system, and the removal system. At study visit 4, after eight hours fasting, 80 subjects will arrive to the pre- assessment unit as part of the theatres at St. Mary's Hospital or Southampton Hospital and receive the EndoBarrier TM Gastrointestinal Liner as part of the EndoBarrier Arm Intervention.
Intervention: EndoBarrier TM Gastrointestinal Liner (Device)
Medical Therapy Arm
The standard medical therapy arm will be carried out in accordance with the guidelines of the American Diabetes Association. These guidelines have been chosen as they are applicable to an International audience and thus would adhere to the current best worldwide practice that would still be likely to be relevant when the results are published following study completion.
Diabetes reviews appointments with a Diabetologist/Endocrinologist will be performed with the control arm patients at visits 2, 4, 6, 7, 9, 11, 12, 13 and 15.
At study visit 4, 80 subjects will arrive at Mary's Hospital or Southampton Hospital and receive the best Medical Care and dietary advice as part of the Medical Therapy Arm Interventions.
Intervention: Best Medical Care (Other)
Outcomes
Primary Outcomes
HbA1c reduced by 20%
Time Frame: 2 years
To compare the EndoBarrier with conventional medical therapy, diet and exercise for obesity related type II diabetes and their effectiveness on metabolic state as defined by the International Diabetes Federation (IDF) with an HbA1c reduced by 20%.
Secondary Outcomes
- HbA1c < 6% ( or < 42 mmol/mol)(2 years)
- Blood pressure < 135/85(2 years)
- Absolute weight loss(2 years)
- Changes in brain reward systems before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier.(2 years)
- Changes in body fat content before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier.(2 years)
- Changes in gut hormones before and after the EndoBarrier device(2 years)
- Changes in gut microbiome before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier.(2 years)
- Changes in food preference before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier.(2 years)
- Changes in biomarkers such as genetic markers before and after the EndoBarrier device(2 years)
- Changes in hepatic or peripheral insulin sensitivity before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier(2 years)
- To estimate the cost-effectiveness of the EndoBarrier device compared with conventional treatment.(2 years)