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Trial record 3 of 6 for:    3393032 [PUBMED-IDS]

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
Sponsor:
Collaborators:
National Institute for Health Research, United Kingdom
University Hospital Southampton NHS Foundation Trust
Brunel University
University of Surrey
Information provided by (Responsible Party):
Imperial College London

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.

Condition or disease Intervention/treatment Phase
Overweight and Obesity Diabetes Device: EndoBarrier TM Gastrointestinal Liner Other: Best Medical Care Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. HbA1c < 6% ( or < 42 mmol/mol) [ Time Frame: 2 years ]
    HbA1c < 42 mmol/mol

  2. Blood pressure < 135/85 [ Time Frame: 2 years ]
    Blood pressure < 135/85

  3. Absolute weight loss [ Time Frame: 2 years ]
    Absolute weight loss

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-65 years (male or female)
  2. T2DM for at least 1 year (HbA1c 7.5-10.0% = 58-86 mmol/mol)
  3. On oral T2DM medications (metformin is allowed, but not required)
  4. BMI 30-50 kg/m2 with adequate insulin reserve as indicated with insulin C-peptide levels > 1665 pmol/L

Exclusion Criteria:

  1. Language barrier, mental incapacity, unwillingness or inability to understand and be able to complete questionnaires
  2. Non-compliance with eligibility criteria
  3. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate or reliable contraceptive methods
  4. Current use of insulin
  5. Previous diagnosis with Type 1 DM or a history of ketoacidosis
  6. Requirement of NSAIDs (non-steroidal anti-inflammatory drugs) or prescription of anticoagulation therapy during the implant period
  7. History of iron deficiency and/or iron deficiency anaemia
  8. Symptomatic gallstones or kidney stones at the time of screening
  9. History of coagulopathy, upper gastro-intestinal bleeding conditions such as oesophageal or gastric varices, congenital or acquired intestinal telangiectasia
  10. Previous GI surgery that could affect the ability to place the device or the function of the implant
  11. 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)
  12. Family history of a known diagnosis or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
  13. 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
  14. Severe depression, unstable emotional or psychological characteristics (indicated by Beck Depression Inventory II score >28)
  15. Poor dentition and inability to adequately chew food
  16. Planned holidays up to three months following the EndoBarrier Implant
  17. Previous EndoBarrier implantation
  18. Metal implant unsuitable for MRI scanning and claustrophobia as contraindications for MRI scans (sub-group 1 - fMRI study only)
  19. Vegetarian, vegan, gluten or lactose intolerance as unsuitable for fMRI food picture paradigm (sub-group 1 - fMRI only)

Information from the National Library of Medicine

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


Locations
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United Kingdom
Imperial Clinical Trials Unit
London, United Kingdom, W2 1PG
Sponsors and Collaborators
Imperial College London
National Institute for Health Research, United Kingdom
University Hospital Southampton NHS Foundation Trust
Brunel University
University of Surrey
Investigators
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Principal Investigator: Julian Teare, Professor Imperial College London

Additional Information:
Publications of Results:
Cohen, R., et al. Endoscopic Duodenal-Jejunal Bypass: Effect on Insulin Sensitivity in Mildly Obese Diabetic Subjects. in 72nd Scientific Sessions American Diabetes Association (Philadelphia, USA, 2012).
Association, A.D. Standards of Medical Care in Diabetes—2013. Diabetes care 36, S11-S66 (2013).
van Strien, T., Frijters, J.E.R., Bergers, G.P.A. & Defares, P.B. The Dutch Eating Behavior Questionnaire (DEBQ) for assessment of restrained, emotional, and external eating behavior. Int J Eat Disorder 5, 295-315 (1986).
Babor, T., Higgins-Biddle, J., Saunders, J. & Monteiro, M. AUDIT: The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Care. (2001).
Haidt, J., Mccauley, C. & Rozin, P. Individual-Differences in Sensitivity to Disgust - a Scale Sampling 7 Domains of Disgust Elicitors. Pers Indiv Differ 16, 701-713 (1994).

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT02459561     History of Changes
Other Study ID Numbers: 14SM2015
First Posted: June 2, 2015    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Keywords provided by Imperial College London:
Obesity
Diabetes
Overweight
Medical device
Endobarrier
Clinical trial
Diet
Exercise
Body weight
Medical therapy
Medicine
Device
Randomised
Control
Intervention
EndoBarrier Medical device
Additional relevant MeSH terms:
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Diabetes Mellitus
Overweight
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms