Efficacy and Safety of One-anastomosis Versus Roux-en-Y Gastric Bypass for Type 2 Diabetes Remission

Study Overview
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Brief Summary
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Diabetes mellitus (T2DM) is the most common complication of obesity patients. According to previous literature reports, weight loss and metabolic surgery are powerful means to treat obesity complicated with T2DM. Roux-en-Y gastric bypass (RYGB) is the standard operation recommended by the international society. One-anastomosis gastric bypass (OAGB) was recommended by IFSO（the International Federation for the Surgery of OBESITY AND METABOLIC DISORDERS ） in 2018. In this study, two kinds of metabolic surgery will be compared. At present, focusing on the above two operations, only two effective randomized controlled clinical studies have been carried out, among which one single-center clinical study has been followed up for 2 years, and the primary end point is weight loss; Another multicenter study, with a 2-year follow-up, showed that the primary end point was weight loss, and the secondary index was the effectiveness of two surgical methods in the treatment of T2DM.There is still a lack of evidence-based evidence for the effectiveness and safety of the two surgical methods in the treatment of T2DM. This study will make high-level evidence about the advantages and disadvantages of OAGB and RYGB in the treatment of T2DM. In this study, a number of centers with rich experience and clinical research experience in weight loss and metabolic surgery in Asia will be combined to complete the enrollment of 248 patients. Those who meet the standards will be randomly divided into two kinds of operations, and they will be followed up for 5 years on schedule. The rate of lost follow-up is controlled within 20%, and the data integrity is controlled within 95%. Taking the blood glucose remission rate of type 2 diabetes as the main observation index, the prospective verification shows that OAGB is clinically effective in treating obesity with type 2 diabetes compared with RYGB.

Official Title
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Efficacy and Safety of One-anastomosis Versus Roux-en-Y Gastric Bypass for Type 2 Diabetes Remission (ORDER): a Multi-centric, Randomized, Open-label, Superiority Trial

Conditions
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Type2 Diabetes, Complication of Bariatric Procedure

Intervention / Treatment
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* Procedure: The laparoscopic One-anastomosis gastric bypass will consist of:
* Procedure: The laparoscopic Roux-en-Y gastric bypass will consist of:


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21-65 years old, Male/Female, East Asian population 50 kg/m2≥BMI≥27.5kg/m2 Type 2 diabetes duration ≥6 months HbA1c≥7.0% Currently receiving one or more oral/injectable hypoglycemic drugs (insulin /glucagon-like peptide-1 receptor agonist) Recommendation for OAGB/RYGB evaluated by a multidisciplinary team Exclusion Criteria: Underwent gastrointestinal surgery (gastric/duodenal surgery or bariatric surgery) Fasting C-peptide level lower than 1/2 normal minimum Active gastrointestinal ulcer is present Helicobacter pylori infection is present A history of serious cardiovascular and cerebrovascular diseases (myocardial infarction, stroke, etc.) A history of cirrhosis (Child-Pugh≥A) A history of chronic kidney disease (eGFR )< 60 ml/min / 1.73 m2) Inflammatory bowel disease is present (ulcerative colitis, Crohn's disease) Chronic anemia is present, Hgb for male <100g/L, for female <90g/L A desire to conception during the study period Uncontrolled mental and psychological disorders are present Expected survival<5 years of end-stage disease or previous/current malignant tumor Participated in clinical studies/trials that have the conflict of interest with the study Unable to understand, refuse to participate and sign the informed consent Gallstones require cholecystectomy Reflux esophagitis above grade A

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Experimental: Laparoscopic One-anastomosis gastric bypass<br>In this group, the bariatric procedure is laparoscopic one-anastomosis gastric bypass, all operations follow the same standard operating procedure. | Procedure: The laparoscopic One-anastomosis gastric bypass will consist of:<br>* gastrointestinal anastomosis: anterior colon and posterior stomach gastrointestinal anastomosis size: diameter < 1.5cm, linear anastomosis length 2.5cm biliary and pancreatic branches 200cm, food branches 100cm exact relationship with mesangial defect<br>|
| Active Comparator: Laparoscopic Roux-en-Y gastric bypass<br>In this group, the bariatric procedure is laparoscopic Roux-en-Y gastric bypass, all operations follow the same standard operating procedure. | Procedure: The laparoscopic Roux-en-Y gastric bypass will consist of:<br>* the laparoscopic Roux-en-Y gastric bypass gastric sac size < 30ml gastrointestinal anastomosis: anterior colon and posterior stomach gastrointestinal anastomosis size: diameter < 1.5cm, linear anastomosis length 2.5cm biliary and pancreatic branches 50cm, food branches 150cm exact relationship with mesangial defect<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year after operation, the complete remission rate of type 2 diabetes mellitus [HbA1c < 6%, fasting plasma glucose < 5.6 mmol/L, no need to use any hypoglycemic drugs] | Complete remission of type 2 diabetes mellitus: the blood sugar HbA1c<6.0% and fasting plasma glucose< 5.6 mmol/L can be controlled only by changing lifestyle intervention without taking hypoglycemic agents after operation. Partial remission: blood glucose can be controlled only by changing lifestyle intervention after operation. HbA1c<6.5%, fasting plasma glucose 5.6 6.9mmol/L, and blood glucose 7.8 11.0mmol/L 2 hours after meal. Failure: blood sugar was relieved once, and then returned to the preoperative level.Unified OGTT measurement method | 1 year after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The remission rate of type 2 diabetes mellitus | [HbA1c < 6%, with or without hypoglycemic drugs] Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| The change of HbA1c | Changes of glycosylated hemoglobin (HbA1c) compared with baseline.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| HbA1c value | The value of HbA1c.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| The change of fasting blood glucose | Changes of fasting blood glucose compared with baseline.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Fasting blood glucose level | The fasting blood glucose level.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Fasting plasma insulin | The value of fasting plasma insulin.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Diabetes medication | Follow up was used to observe whether the dosage of postoperative diabetes was reduced.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Fasting blood lipids | The value of fasting blood lipids.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Changes of arterial blood pressure (SBP, DBP) | The change of arterial blood pressure (SBP, DBP).Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| The excess weight loss (%EWL) and the total weight loss (%TWL) after surgery. | %EWL=[(initial weight)-(post-op weight)]/[(initial weight)-(ideal weight)] (in which ideal weight is defined by the weight corresponding to a BMI of 25 kg/m2),%TWL=[(initial weight)-(post-op weight)]/initial weight.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Change waist circumference (cm) according to absolute waist circumference | Change waist circumference (cm) according to absolute waist circumference.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Incidence of medical and surgical complications | Incidence of medical and surgical complications (anastomotic leakage, bile reflux, intestinal obstruction, anastomotic ulcer, anastomotic stenosis, internal hernia, chronic gastritis, esophagitis, iron deficiency anemia ...) Visit 1:Post-op 1 month (+7 Days) Visit 2: Post-op 3 months(+7 Days) Visit 3: Post-op 6 months(14 Days) Visit 4: Post-op 12 months (+30 Days) Visit 5：Post-op 24 months (±30 Days) Visit 6:Post-op 36 months (±30 Days) Visit 7：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Incidence of surgical complications | According to the grade of surgical complications, proportion of surgical complications in the total number.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 
| Surgery time | Surgery time.Visit 1: Surgery day (day 0) record | Surgery day (day 0) record | 
| Average length of stay, based on the length of stay from operation (surgery day =day0) to the end of hospitalization | Average length of stay, based on the length of stay from operation (surgery day =day0) to the end of hospitalization.Visit 1: Surgery day (day 0) record | 30 days after surgery | 
| Postoperative quality of life of patients, according to Impact Weight Quality Of Life questionnaire for weight loss surgery, scores were obtained | According to Impact Weight Quality Of Life questionnaire for weight loss surgery, scores were obtained.The higher the score, the better the quality of life. Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | One day before surgery,5 years after surgery | 
| Postoperative gastroesophageal reflux | Evaluate according to gastroesophageal reflux disease questionnaire. The higher the score, the more likely there is gastroesophageal reflux. Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | One day before surgery,5 years after surgery | 
| Diarrhea frequency | Based on gastrointestinal symptom rating scale.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | One day before surgery,5 years after surgery | 
| Dumping syndrome and hypoglycemia symptoms | Dumping syndrome and hypoglycemia symptoms.Dumping syndrome and hypoglycemia symptoms will be evaluated by questionnaire.Visit 1: Baseline Visit (Day 0-1) Visit 2:Post-op 1 month (+7 Days) Visit 3: Post-op 3 months(+7 Days) Visit 4: Post-op 6 months(14 Days) Visit 5: Post-op 12 months (+30 Days) Visit 6：Post-op 24 months (±30 Days) Visit 7:Post-op 36 months (±30 Days) Visit 8：Post-op 60 months (±30 Days) | 5 years after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bariatric surgery