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临床试验/NCT03330756
NCT03330756Unknown不适用

The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and the Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus and the Pathophysiological Mechanisms That Drive the Conversion of Malign to Benign Obesity

Slotervaart Hospital1 个研究点 分布在 1 个国家目标入组 220 人开始时间: 2017年10月23日最近更新:
适应症
干预措施

试验速览

阶段
不适用
发起方
入组人数
220
试验地点
1
主要终点
glycaemic control

研究概览

简要总结

It is estimated that there will be 439-552 million people with type 2 diabetes mellitus (T2DM) globally in 2030. Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. It is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH). It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown.Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

详细描述

Metabolic surgery has proven to be a viable long-term solution in the treatment of morbid obesity and its comorbidities. It induces rapid remission of type 2 diabetes mellitus (T2DM). Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH), with the latter becoming the major indication for liver transplantation in the USA. It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown. Also, it is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB), an efficient but complex procedure, is the golden standard in the Netherlands. The Laparoscopic Mini Gastric Bypass (LMGB) is technically less challenging and has been introduced to overcome some of the limitations of LRYGB. It has been hypothesized that the LMGB has a more rapid and durable glycaemic control, possibly due to the altered constitution and the augmented length of the biliary limb. There is reason to believe that the improved glycaemic control might become apparent within the first year of surgery and that it might remain thereafter. However, it is unknown what order of magnitude is to be expected and whether subgroups of T2DM patients will benefit the LMGB more. Also, it is unknown whether and to what extent intestinal microbiota and immunological tone can predict the metabolic response (improvement in insulin sensitivity) and NAFLD/NASH reduction and whether differences are expected between these two surgeries. Increased understanding of the pathophysiological mechanisms as well as their relationship to metabolic disturbances are thought to be of crucial importance to discover new diagnostic and therapeutical targets in obesity associated insulin resistance/T2DM and NAFLD/NASH. Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
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

  • •BMI ≥35 and ≤50 kg/m2
  • •Diagnosis and treatment of T2DM at intake at bariatric ward with use of anti-diabetic medication.
  • •American Society of Anaesthesiologist Classification (ASA) ≤3
  • •All patients are required to lose 6 kilograms of weight prior to surgery

排除标准

  • •Known genetic basis for insulin resistance or glucose intolerance
  • •Type 1 DM
  • •Prior Bariatric surgery
  • •Patients requiring a concomitant intervention (such as cholecystectomy, ventral hernia repair)
  • •Auto-immune gastritis
  • •Known presence of gastro-esophageal reflux disease
  • •Known presence of large hiatal hernia requiring concomitant surgical repair
  • •Coagulation disorders (PT time > 14 seconds, aPTT ((dependent on laboratory methods) or known presence of bleeding disorders (anamnestic))
  • •Known presence of hemoglobinopathy
  • •Uncontrolled hypertension (RR > 150/95 mmHg)
  • •Renal insufficiency (creatinine > 150 umol/L)
  • •Pregnancy
  • •Breastfeeding
  • •Alcohol or drug dependency
  • •Primary lipid disorder
  • •Participation in any other (therapeutic) study that may influence primary or secondary outcomes

研究组 & 干预措施

Laparoscopic Roux-en-Y gastric bypass

Active Comparator

Laparoscopic Roux-en-Y gastric bypass

干预措施: laparoscopic Roux-en-Y gastric bypass (Procedure)

Laparoscopic Mini Gastric Bypass

Experimental

laparoscopic Mini gastric bypass

干预措施: laparoscopic Mini gastric bypass (Procedure)

结局指标

主要结局

glycaemic control

时间窗: 12 months FU

as measured by the difference in HBa1C

次要结局

  • Expression and differentiation of inflammatory markers(12 and 24 months FU)
  • Eating habits(baseline, 12, 24 months FU)
  • NAFLD/NASH(day of surgery, reoperation)
  • Expression and differentiation of intestinal immunological cells - GALT(day of surgery, reoperation)
  • Presence of bacterial DNA/bacterial metabolites - portal vein(day of surgery, reoperation)
  • Expression and differentiation of intestinal immunological cells - abdominal adipose tissue(day of surgery, reoperation)
  • Expression and differentiation of immunological cells(12 and 24 months FU)
  • Small intestinal and fecal microbiota composition(2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery)
  • Excreted metabolites(baseline, 12, 24 months FU)
  • Quality of life(baseline, 12, 24 months FU)
  • Insulin sensitivity(baseline, 12, 24 months FU)
  • Presence of bacterial DNA/bacterial metabolites - abdominal adipose tissue(day of surgery, reoperation)
  • Expression and differentiation of intestinal immunological cells - liver(day of surgery, reoperation)
  • Expression and differentiation of intestinal immunological cells - peripheral blood(day of surgery, reoperation)
  • Peripheral blood inflammatory markers(2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery)
  • Bio electric impedance(baseline, 12, 24 months FU)
  • glycaemic control(6, 12 and 24 months FU)
  • Presence of bacterial DNA/bacterial metabolites - liver(day of surgery, reoperation)
  • Cardiac / ventricular hypertrophy(baseline, 12, 24 months FU)
  • glycaemic control(6 and 24 months FU)

研究者

发起方
Slotervaart Hospital
申办方类型
Other
责任方
Sponsor

研究点 (1)

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