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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Type2 Diabetes; Complication of Bariatric Procedure
• Intervention / Treatment: Procedure: The laparoscopic One-anastomosis gastric bypass will consist of:; Procedure: The laparoscopic Roux-en-Y gastric bypass will consist of:

• Study Type: Interventional
• Enrollment (Anticipated): 248
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhongtao Zhang, M.D.;Ph.D; Phone Number: +86-13801060364; Email: zhangzht@ccmu.edu.cn
• Study Contact Backup: Name: Mengyi Li, M.D; Phone Number: +86-15810993198; Email: limengyi@ccmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital
      • Contact: Zhongtao Zhang, M.D.;Ph.D; Phone Number: +86-13801060364; Email: zhangzht@ccmu.edu.cn
      • Principal Investigator: Zhongtao Zhang, M.D.;Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparoscopic One-anastomosis gastric bypass; 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: 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
Active Comparator: Laparoscopic Roux-en-Y gastric bypass; 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: 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Beijing Tiantan Hospital; Taipei Medical University Hospital; The First Affiliated Hospital of Soochow University; The Third Xiangya Hospital of Central South University; Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University; Shanghai Jiao Tong University Affiliated Sixth People's Hospital; The Third People's Hospital of Chengdu
• Investigators: Principal Investigator: Zhongtao Zhang, M.D.;Ph.D, Beijing Friendship Hospital

Publications and helpful links

General Publications

• Li M, Liu Y, Lee WJ, Shikora SA, Robert M, Wang W, Wong SKH, Kong Y, Tong DKH, Tan CH, Zeng N, Zhu S, Wang C, Zhang P, Gu Y, Bai R, Meng F, Mao Z, Zhao X, Wu L, Liu Y, Zhang S, Zhang P, Zhang Z. Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for type 2 diabetes remission (ORDER): protocol of a multicentre, randomised controlled, open-label, superiority trial. BMJ Open. 2022 Sep 29;12(9):e062206. doi: 10.1136/bmjopen-2022-062206.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): October 1, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: August 15, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Bariatric surgery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: BFH-ORDER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Will individual deidentified participant data (including data dictionaries) will be shared: Yes; what data in particular will be shared: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).; what other documents will be available: study portocol; when will data be availuble (start and end dates): Beginning 6 months and ending 24 months following article publicaiton.; With whom: Investigators whose proposed use of the data has been approved by an independent review commmittee identified for this purepose.; For what types of analysis: For individual participant data meta-analysis.; By what mmechanism will data be made available: Proposals should be directed to zhangzht@ccmu.edu.cn to gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: Beginning 6 months and ending 24 months following article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No