EndoBarrier TM Gastrointestinal Liner Diabetes Trial (EndoBarrier)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02459561|
Recruitment Status : Active, not recruiting
First Posted : June 2, 2015
Last Update Posted : April 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Overweight and Obesity Diabetes||Device: EndoBarrier TM Gastrointestinal Liner Other: Best Medical Care||Not Applicable|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||170 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||March 2015|
|Actual Primary Completion Date :||October 18, 2018|
|Estimated Study Completion Date :||May 15, 2019|
Experimental: 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.
Device: EndoBarrier TM Gastrointestinal Liner
If subjects are randomised into the EndoBarrier Group of the trial they will receive the device for 12 months followed a 12 months follow-up period.
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.
Other: Best Medical Care
If subjects are randomised into the Control Group of the trial they will receive best medical care and dietitian advice for 12 months followed a 12 months follow-up period.
- 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%.
- HbA1c < 6% ( or < 42 mmol/mol) [ Time Frame: 2 years ]HbA1c < 42 mmol/mol
- Blood pressure < 135/85 [ Time Frame: 2 years ]Blood pressure < 135/85
- Absolute weight loss [ Time Frame: 2 years ]Absolute weight loss
- Changes in gut hormones before and after the EndoBarrier device [ Time Frame: 2 years ]To investigate the mechanism of the effect of the EndoBarrier, venous blood samples will be taken at intervals by venepuncture through a cannula placed in the antecubital fossa. Serial plasma levels of glucose and other metabolites, bile acids, glucose, insulin, leptin, gut hormones (including ghrelin, GLP-1, PYY), adipocytokines and markers of insulin resistance, and inflammation will be measured. Assays will be performed by the Dept. of Chemical Pathology at Imperial College Healthcare NHS Trust and by in-house assays, outside contracts and commercial kits for radio-immunoassay and ELISA. These will be measured in the fasted and/or postprandial state for each patient and compared within and between the groups using parametric/non-parametric repeated measures statistical testing. Regressions will be performed with clinical outcomes (i.e. BMI, glucose control) to identify predictive markers and generate mechanistic hypotheses.
- Changes in gut microbiome before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier. [ Time Frame: 2 years ]To investigate the mechanism of the effect of the EndoBarrier, plasma, urine and faecal samples for metabolomics will be collected at visit 3, 5, 8 and 10 and 14. All samples will be analysed using Mass spectroscopy and NMR spectroscopy. Metabolic datasets will be analysed using principal component analysis (PCA) and orthogonal partial least-squares analysis (O-PLS). The metabolic and microbial data will also be analysed in relation to response measurements such as BMI, gut hormone levels and etc. using O-PLS regression analysis and Bayesian approaches. A range of statistical methods will be optimised and applied to the data to identify weight loss and T2DM-associated microbiota and metabolites.
- Changes in brain reward systems before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier. [ Time Frame: 2 years ]Patients will have fMRI scans to examine between brain function related to food reward and addictive behaviours at baseline and early after intervention, and these will be correlated to psychological questionnaires, computerised tasks, and test meals. Comparison of brain activation during fMRI paradigms and outcomes from behavioural measures of food hedonics and questionnaires will be compared between groups using a 2x2 ANOVA design including group (control vs. Endobarrier) between subject factor, time (baseline vs. follow-up visit) within subject factor, and group x time interaction to identify differential effects between groups. In addition linear regression will be performed to measure the correlation of variables at baseline or during the intervention with primary outcomes at 1 year e.g. weight loss and decreases in HbA1c within each group.
- Changes in body fat content before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier. [ Time Frame: 2 years ]As well as baseline anthropometric measurements of height, weight, waist and hip circumference, patients will also have their percentage body fat determined by bio-electrical impedance analysis. This is a painless, safe procedure to measure total body fat involves lying on a bed, having two sticky pads placed on a hand and foot, and lying still for 1 minute, or standing on a metal platform for 1 minute so that the body's electrical resistance can be measured.
- Changes in food preference before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier. [ Time Frame: 2 years ]Sweet taste detection testing: 7 ascending sucrose concentrations in solution will used to determine sweet detection thresholds. The subjects will sample the stimulus in the mouth and then spit the sample in a container to then indicate whether the stimulus was water or not. Consummatory taste reward: 5 ascending fat and sucrose solutions/ice-cream will be used to test responses in intensity ratings and hedonic reward. Participants will be asked to put the solutions into their mouths and then to spit it out into a bucket. While the solution is in the participants' mouths they will be asked to rate its intensity and pleasantness using visual analogue scales. Analysis: Sweet taste detection thresholds and visual analogue taste ratings will be quantified for each patient and compared within and between the groups at 3 time points using parametric/non-parametric repeated measures statistical testing.
- Changes in biomarkers such as genetic markers before and after the EndoBarrier device [ Time Frame: 2 years ]To investigate the mechanism of the effect of the EndoBarrier, blood (15 ml) will be taken to extract DNA and RNA for examination of genetic markers which predict weight loss, genetic abnormalities causing or contributing to obesity and insulin resistance (including array comparative genomic hybridization for copy number variations, epigenetic analysis, whole genome or exome sequencing, DNA sequencing of candidate genes (such as MC4R, POMC, leptin receptor, SIM1); and polymorphisms or mutations associated with obesity, diabetes mellitus, PCOS, fat distribution and body composition (using PCR based SNP analysis)56-58. RNA will be extracted from blood to perform genome-wide expression analysis.
- Changes in hepatic or peripheral insulin sensitivity before and after the EndoBarrier device to investigate the mechanism of the effect of the EndoBarrier [ Time Frame: 2 years ]Patients will undergo a euglycaemic hyperinsulinaemic clamp with stable isotope infusion to determine overall insulin and compartment-specific insulin sensitivity (liver, muscle and adipose depot). Blood samples will be taken every 5 minutes to measure blood glucose concentration and the dextrose infusion will be adjusted accordingly. Overall and tissue specific insulin sensitivity will be quantified for each patient and compared within and between the groups at 3 time points using parametric/non-parametric repeated measures statistical testing. Regressions will be performed with clinical outcomes (i.e. BMI, glucose control) to identify predictive markers and generate mechanistic hypotheses.
- To estimate the cost-effectiveness of the EndoBarrier device compared with conventional treatment. [ Time Frame: 2 years ]To estimate the cost-effectiveness of the EndoBarrier device compared with conventional treatment over the trial period using Quality of Life questionnaires. These comprise the EQ-5D-5L questionnaire to assess health-related quality of life, and a bespoke questionnaire designed to collect information about patients' use of health and social care resources (for costing purposes). The resource use questionnaire has been adapted from existing instruments and will ask patients to specify what services they have used since the previous assessment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02459561
|Imperial Clinical Trials Unit|
|London, United Kingdom, W2 1PG|
|Principal Investigator:||Julian Teare, Professor||Imperial College London|