A randomized controlled trial of a duodenal sleeve bypass device (Endobarrier) compared with standard medical therapy for the management of obese subjects with type 2 diabetes

The International Diabetes Federation (IDF) has recently defined optimization of the metabolic state as an HbA1c of less than 6% with more than 15% weight loss, a blood pressure below 135/85 mmHg and a reduction in the dose/or number of medications. Significant improvement indicates a 20% reduction in HbA1c with less medication. With diet and exercise, in addition to medication, currently few individuals will achieve optimization and there is a need to look at alternative treatment options. Gastric bypass surgery has been proven effective in achieving and maintaining weight loss and improving obesity-related type 2 diabetes. However, there is a need to develop minimally invasive and less costly alternatives to surgical interventions. The EndoBarrier is a removable duodenal-jejunal sleeve device that following endoscopic placement, allows chyme to bypass the proximal intestine in a similar fashion to a surgical bypass. EndoBarrier device placement has been reported to improve blood glucose control and aid weight loss. We will compare current best medical therapy with the EndoBarrier for the control of type 2 diabetes (T2DM).The primary endpoint of this trial is significant improvement of the metabolic state as defined by the IDF with secondary endpoints being weight loss and the frequency of adverse events with the EndoBarrier. The trial will include individuals of 18-65 with T2DM, a BMI of 30-50 kg/m2 with measurable insulin reserve as indicated by insulin c-peptide levels. Exclusion criteria include concomitant use of anticoagulants, non-steroidal anti-inflammatory drugs and significant co-morbidity. Helicobacter pylori will need to be excluded or eradicated prior to inclusion in the EndoBarrier arm. From current trial data 40% of subjects will achieve significant improvement with EndoBarrier and 15% will do so with best medical therapy. The study will thus require 80 subjects in each arm powered at 80% including a 10% loss to follow-up. We will also follow up patients for 12 months after the removal of the EndoBarrier to identify whether any benefits are maintained after removal of the device. Data collection will be co-ordinated by the Imperial Clinical Trials Unit under the guidance of Professor Neil Poulter. The majority of study participants are expected to be recruited from general practices. The NIHR Local Clinical Research Networks will be involved in identifying local GPs to act as Participant Identification Centres and will advise on other approaches to engage patients in the study. Patients will attend Imperial College Healthcare NHS Trust (St Mary’s Hospital) or Southampton General Hospital for the research visits. All individuals will have a baseline visit to ensure eligibility with subsequent randomization by ICTU within a month to either arm. Both groups will receive dietetic and exercise advice. After inclusion, patients will be seen every 3 months during the year-long study period and for 12 months afterwards. At each visit, body weight and blood pressure will be recorded and HbA1c measured. The trial is expected to last for 46 months. The initial 6 months includes time for recruitment of staff, ethical submission and engagement of the NIHR Local Clinical Research Networks and the identification of Participant Identification Centres. This is followed by three periods of 12 months to cover patient recruitment, treatment and follow up. Study close out will be completed in 4 months. To assess the mechanisms of effect of the EndoBarrier we will look at comparing gut hormones, metabonomics, bile acids, food preferences, functional MRI of brain reward systems and peripheral and hepatic insulin sensitivities. Patient involvement in the mechanistic assessments will be optional.