Surgical TreAtment for Obesity Related Disease and Onco-Metabolic Surgery

Study Overview
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Brief Summary
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This is a prospective, multi-center, randomized controlled trial to compare Billroth II reconstruction versus conventional Roux-en-Y reconstruction versus long limb Roux-en-Y reconstruction for glycemic control in patients with concurrent type 2 diabetes and gastric cancer.

Detailed Description
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Billroth I, Billroth II, or Roux-en-Y procedure follows gastrectomy to reconstruct the gastrointestinal tract. Billroth I procedure restores the normal configuration of the gastrointestinal tract and Billroth II and Roux-en-Y procedure involve the creation of duodenal switch which is thought to be responsible for metabolic effects by altering enteric hormones. Accordingly, several retrospective studies reported that Billroth I reconstruction has less effect on diabetes compared to Billroth II and Roux-en-Y reconstruction. While little is known about different effects of Billroth II and Roux-en-Y procedure, a study retrospectively show that Roux-en-Y procedure has significantly higher rate of T2DM remission than Billroth II procedure. Investigators conduct a randomized controlled trial to control possible confounders arising from diverse metabolic effects of cancer and minimize differences in treatment regimen among patients.

Official Title
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A Randomized Controlled Trial Comparing Billroth II Reconstruction Versus Conventional Roux-en-Y Reconstruction Versus Long Limb Roux-en-Y Reconstruction for Glycemic Control in Patients With Concurrent Type 2 Diabetes and Gastric Cancer

Conditions
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Gastric Cancer, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Procedure: Long limb Roux-en-Y reconstruction after subtotal gastrectomy
* Procedure: Conventional Roux-en-Y reconstruction after subtotal gastrectomy
* Procedure: Billroth II reconstruction after subtotal gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Distal gastric adenocarcinoma diagnosed pathologically under preoperative endoscopic biopsy, and clinical stage I-II Body mass index ≥ 23 kg/m2 Type 2 diabetes and HbA1c ≥ 6.5% Exclusion Criteria: Insulin usage for glycemic control at the time of screening evaluation Prior gastrointestinal surgery including splenectomy, hepatobiliary and pancreatic surgery (except hemorrhoidectomy, herniorrhaphy, and appendectomy) Abdominal, thoracic, pelvic and/or obstetric-gynecologic surgery within 3 months Cardiovascular conditions including significant known CAD, uncompensated congestive heart failure, history of stroke, or uncontrolled hypertension. Subjects with CAD that have been successfully treated with CABG or PCI, and have no evidence of active ischemia are eligible Kidney disease including renovascular hypertension, renal artery stenosis, or end-stage renal disease Chronic liver disease including liver cirrhosis, alpha-1 antitrypsin deficiency Gastrointestinal disorders including inflammatory bowel disease (Crohn's disease or ulcerative colitis) or any malabsorptive disorders Psychiatric disorders including dementia, active psychosis, history of suicide attempts, alcohol or drug abuse within 12 months Severe pulmonary disease defined as FEV1 <50% of predicted value Anemia defined as hemoglobin less than 8 in females and 10 in males Malignancy within 5 years (except squamous cell and basal cell cancer of the skin). Subjects diagnosed with early or stage I cancer than have been successfully treated are eligible per investigator discretion Frail elderly (Rockwood Clinical Frailty Scale ≥5) Any condition or major illness that, in the investigator's judgement, places the subject at undue risk by participating in the study Unable to understand the risks, realistic benefits and compliance requirements of each program Use of investigational therapy or participation in any other clinical trial within 3 months Geographic inaccessibility Pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Long limb Roux-en-Y reconstruction<br>Long limb Roux-en-Y reconstruction method follows subtotal gastrectomy for gastric cancer. | Procedure: Long limb Roux-en-Y reconstruction after subtotal gastrectomy<br>* The jejunum will be divided approximately 150 cm distal to the ligament of Treitz (Length of biliopancreatic limb). The gastrojejunostomy will be performed by end-to-end anastomosis and an anastomosis of the proximal end of the jejunum to the distal jejunum will be created approximately 50 cm distal from the gastrojejunal anastomosis (Length of Roux-en-Y limb).<br>|
| Active Comparator: Conventional Roux-en-Y reconstruction<br>Conventional Roux-en-Y reconstruction method follows subtotal gastrectomy for gastric cancer. | Procedure: Conventional Roux-en-Y reconstruction after subtotal gastrectomy<br>* The jejunum will be divided approximately 20 cm distal to the ligament of Treitz (Length of biliopancreatic limb). The gastrojejunostomy will be performed by end-to-end anastomosis and an anastomosis of the proximal end of the jejunum to the distal jejunum will be created approximately 30-45 cm distal from the gastrojejunal anastomosis (Length of Roux-en-Y limb).<br>|
| Active Comparator: Billroth II reconstruction<br>Billroth II reconstruction method follows subtotal gastrectomy for gastric cancer | Procedure: Billroth II reconstruction after subtotal gastrectomy<br>* The duodenum will be transected approximately 2 cm distal to the pylorus and anastomosis will be performed between the gastric remnant and a loop of jejunum chosen approximately 20 cm distal to the ligament of Treitz (Length of afferent loop)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The success rate of biochemical improvement of diabetes as measured by HbA1c < 6.5% | The proportion of subjects with HbA1c < 6.5% without diabetes medications | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first occurence of glycated hemoglobin < 6.5% (or 6.0%) | The number of days from randomization to the visit date when HgA1c is first observed to be < 6.5% (or 6.0%) post-randomization | Every visit date, assessed up to 12, 24, and 36 months | 
| Success rate of biochemical resolution of diabetes | Success rate of biochemical improvement of diabetes at 12, 24, 36 months as measured by HbA1c ≤ 6% (with or without diabetes medication) | 12 months, 24 months, 36 months | 
| Success rate of biochemical improvement of diabetes | Success rate of biochemical improvement of diabetes at 12, 24, 36 months as measured by HbA1c <6.5% (with or without diabetes medication) | 12 months, 24 months, 36 months | 
| Change in glycated hemoglobin from baseline | percent change | 12 months, 24 months, 36 months | 
| Change in fasting plasma glucose level from baseline | percent change | 12 months, 24 months, 36 months | 
| Change in total cholesterol | Percent change in total cholesterol at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| Change in triglyceride | Percent change in triglyceride at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| Change in High-density Lipoprotein (HDL) | Percent change in high-density lipoprotein (HDL) at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| Change in Low-density Lipoprotein (LDL) | Percent change in Low-density Lipoprotein (LDL) at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| Use of diabetes medication | number of diabetes medication at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| Patients with hypertension and/or requiring antihypertensive therapy | number and percentage | 12 months, 24 months, 36 months | 
| Patients with dyslipidemia and/or requiring cholesterol lowering medications | number and percentage | 12 months, 24 months, 36 months | 
| Mean and change in weight and BMI from baseline | mean and percent change | 12 months, 24 months, 36 months | 
| Mean and change in waist, hip, and thigh circumference from baseline | mean and percent change | 12 months, 24 months, 36 months | 
| Change in SF-36 scores of questionnaire from baseline | The MOS 36-Item Short-Form Health Survey | 12 months, 24 months, 36 months | 
| Change in High-sensitivity C-reactive Protein (Hs-CRP) | percent change in high-sensitivity C-reactive protein (hs-CRP) | 12 months, 24 months, 36 months | 
| Change in Systolic Blood Pressure (SBP) | Change in Systolic Blood Pressure (SBP) at 12 months, 24 months, 36 months | 12 months, 24 months, 36 months | 
| The Side Effects and /or Complications of each surgical procedure | number of the Side Effects and /or Complications of each surgical procedure | 12 months, 24 months, 36 months | 
| The success rate of biochemical improvement of diabetes as measured by HbA1c < 6.5% | The proportion of subjects with HbA1c < 6.5% without diabetes medications | 24 months, 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Diabetes Mellitus, Type 2, Subtotal Gastrectomy