Endobarrier Treatment in Obese Subjects With T2DM
试验速览
- 阶段
- 4 期
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- percent change in HbA1c level
研究概览
简要总结
Diabesity (Diabetes accompanied by obesity) is a prevalent condition many times complicated by micro- and macrovascular disease. Many treatments for Diabesity paradoxically cause further weight gain and hypoglycemia. The Endobarrier enables diabetes control along with weight loss as an alternative to bariatric surgery for patients who are not interested or not qualified for surgery. The aim of this study is to assess the efficacy and safety of the Endobarrier Diabesity patients in Israel.
This study will include 45 men and women between the ages of 18-65 with HbA1c level of 8% and above and a BMI of 30 kg/m2 or above.
Exclusion criteria: use of anti-coagulant, use of steroids or inability to discontinue these medications.
The cohort will be followed for two years during which the patients will be monitored for diabetes control (by using a continuous glucose monitor), weight, blood pressure, lipid profile, fatty liver (by Ultrasound and blood markers for inflammation and fibrosis) and change in plasma gut peptide levels. The Endobarrier will be explanted after one year, however the monitoring of the patients will continue for another year.
详细描述
Current therapies including diet, exercise, behavior modifications, oral diabetes agents, and insulin, are employed to control Type 2 Diabetes mellitus (T2DM), but rarely return subjects to euglycemia, require dose escalation over time and can be associated with hypoglycemia and weight gain. Obesity is a well-established risk for both the development of diabetes as well as for increased mortality. The majority of individuals with T2DM are overweight or obese. Obesity and type 2 diabetes mellitus are common and well documented risk factors for non-alcoholic fatty liver disease (NAFLD). For some patients NAFLD disease is a relatively benign condition, for others NAFLD will progress to cirrhosis and end-stage liver disease with associated complications including hepatocellular carcino.The current treatment for NAFLD and nonalcoholic steatohepatitis (NASH) is weight reduction which can be achieved by life style modifications, drug therapy or bariatric surgery. The Fibro Test and Fibro Max have proven their efficacy as noninvasive biomarkers for NAFLD and NASH in large scale studies. Transient Elastography which measures liver stiffness non-invasively has been successful in identifying fibrosis in NAFLD.
In addition, designated sonography is a sensitive noninvasive method for steatosis quantification which can diagnose small amounts of liver fat that would be missed by conventional sonography and is not affected by fibrosis or steatohepatitis.
Bariatric Surgery for T2DM In light of this, bariatric surgery has recently emerged as one of the most effective means of providing durable, clinically-significant resolution of diabetes. The majority of subjects with T2DM who undergo these procedures have remission of this disorder. In a large bariatric surgery meta-analysis published in Journal of the American Medical Association in 2004, within studies reporting resolution of diabetes, 76.8% of subjects experienced complete resolution; within studies reporting both resolution and improvement or only improvement of diabetes, 85.4% of subjects experienced resolution or improvement of diabetes. All bariatric operations result in remarkable improvement in T2DM although with varying degrees of efficacy. Resolution of diabetes often occurs within days following bariatric surgery, even before marked weight loss is achieved. Resolution of diabetes is more prevalent following the more "malabsorptive" procedures (BPD or duodenal switch) and the mixed malabsorptive/restrictive Roux-en-y (RYGB) in contrast to the purely restrictive vertical banded gastroplasty (VBG) and laparoscopic adjustable gastric banding (LAGB) procedures. In addition, there appears to be a gradation of diabetes resolution as a function of the operative procedure: 98.9% for BPD, 83.7% for RYGB, 71.6% for VBG, and 47.9% for LAGB. Subjects with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery, suggesting that early surgical intervention is warranted to increase the likelihood of rendering subjects euglycemic. Recently, it has been published that subjects with long-standing uncontrolled diabetes and non-morbid obesity have a high remission rate (88%) of their diabetes following RYGB surgery. However, despite the considerable effectiveness shown by bariatric surgery in resolving diabetes, surgery has not yet become a standard of care for subjects who are obese with diabetes. In part because of an incomplete understanding of the mechanisms of action, this concept of gastrointestinal surgery as an endocrine modifier is not yet fully embraced by the clinical community and has yet to be incorporated into care strategies.12 But perhaps more importantly, some clinicians evoke the irreversibility of gastric bypass and the occasional reports of poor outcomes to label this approach "extreme" - to be reserved as a treatment of last resort.
Bariatric Surgery for NAFLD Weight loss following bariatric surgery results in a marked improvement in hepatic steatosis. An analysis of numerous paired biopsy studies reveals convincing evidence that significant improvement in steatosis and inflammation occurs in NAFLD patients after weight loss surgery. Regression and histologic improvement of NASH has been documented after bariatric surgery.
The "EndoBarrier" Gastrointestinal Liner System is an endoscopically-delivered device that offers an alternative to gastric bypass surgery. The device shields the duodenum and upper jejunum from contact with chyme, thereby mimicking the foregut bypass effect of a RYGB procedure without altering the subject's anatomy. Pancreatic and biliary secretions pass along the outside of the device and then mix with chyme in the upper jejunum. Based on animal experiments and clinical observations, the EndoBarrier device may provide a useful non-surgical intervention for treating T2DM, with an added benefit of weight loss. To date, over 13 studies enrolling over 500 subjects were performed with the EndoBarrier device. In one study, at 12 months 23/32 uncontrolled T2DM subjects (71.9%), were able to achieve an HbA1c value less than or equal to 7.0%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects willing to comply with study requirements and have signed an informed consent form.
- •BMI ≥ 30 kg/m²
- •HbA1c% as assessed by central laboratory ≥ 8.0%.
- •Documented negative pregnancy test in women of childbearing potential.
- •Women of childbearing potential agree to remain on contraceptives for the duration of their trial participation.
排除标准
- •Subjects taking systemic corticosteroids or drugs known to affect GI motility within 30 days prior to randomization
- •Subjects receiving any prescription or over the counter weight loss medication within 30 days prior to randomization (including GLP-1 analogs).
- •Previous GI surgery that could preclude the ability to place the EndoBarrier device, liner or affect the function of the implant
- •Subjects with a history of abnormal GI anatomical findings documented on imaging study, which in the opinion of the Investigator, may impair implantation of the EndoBarrier device
- •Subjects with active GERD not taking a Proton Pump Inhibitor (PPI)
- •Subjects with symptomatic kidney stones within 6 months prior to randomization.
- •Known abnormal pathologies or conditions of the gastrointestinal tract, including ulcers or Crohn's disease, atresias or stenoses, upper gastro-intestinal bleeding conditions
- •Subjects with symptomatic gallstones within 6 months prior to randomization
- •Coagulopathy defined as hgb <10g/dl and platelet < 100,000/ml or diagnosis of hemophilia, factor X deficiencies or fibrinogen abnormalities
- •Any documented history of acute or chronic pancreatitis
- •Subjects requiring prescription antithrombotic therapy (i.e. anticoagulant or antiplatelet agent)
- •Subjects unable to discontinue Aspirin or any other NSAIDs (non-steroidal anti-inflammatory drugs) or any other drugs with bleeding as a potential side effect (i.e coumadin) during the study duration
- •Known diagnosis of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder
- •Subject is or has been enrolled in another investigational study within 3 months of participation into the EndoBarrier study
- •Subjects with poor dentition who cannot completely chew their food.
- •Subjects with thyroid disease unless controlled with a therapeutic dose of medication and have normal thyroid function tests for a minimum of 6 months prior to randomization
- •Subjects not residing within a 3 hour driving distance of the study center.
- •Subjects with an abnormal laboratory or ECG abnormality which the investigators deems clinically significant and makes the patient a poor candidate for the study
- •Subjects with known allergies or hypersensitivity to ceftrixone, cephalosporins or penicillin
结局指标
主要结局
percent change in HbA1c level
时间窗: 1 year, 2 years
percent change in BMI
时间窗: 1 year, 2 years
次要结局
- percent change in LDL cholesterol levels(1 year, 2 years)
- change in waist circumference(1 year, 2 years)
- change in fasting plasma glucose level(1 year, 2 years)
- percent change in HDL cholesterol levels(1 year, 2 year)
- percent in Triglycerides levels(1 year, 2 years)