Comparisons of Metabolic Effect of Sleeve Gastrectomy With Duodenojejunal Bypass and Sleeve Gastrectomy (MEDUSA): A Multicenter Randomized Controlled Trial

Study Overview
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Brief Summary
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In this study, the effects of SG with DJB and SG alone for the treatment of type 2 diabetes mellitus (T2DM) will be compared in patients other than the two groups at both extremes who are expected to show excellent effects of metabolic surgery with SG alone (mild T2DM) and who need SG with DJB (severe T2DM). This study is to target patients with poor blood sugar control despite current medical treatment, although the beta-cell function of the pancreas is preserved. Therefore, this study is aimed at patients who have been using insulin for less than 10 years with T2DM, or taking diabetic medications with HbA1c ≥ 7.0% for less than 10 years with T2DM. The investigators hypothesize that the treatment effects of SG with DJB for T2DM will be superior to that of SG in this group

Detailed Description
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Most Asian patients undergoing metabolic surgery for the treatment of T2DM have BMI as low as 30-35 kg/m2. If SG is performed for the treatment of T2DM in these patients, weight may decrease after the surgery; however, T2DM may recur after 6 months to 1 year. Therefore, it is difficult to find clinical studies on SG for metabolic surgery in Asians, and gastric bypass may be more appropriate as metabolic surgery. However, gastroscopy for the remnant stomach after gastric bypass is practically impossible. Therefore, gastric bypass may be a fatal drawback for East Asian patients with a high incidence of gastric cancer. In recent years, modified duodenal switch (SG with duodenojejunal bypass [DJB], which is defined as the procedure that makes jejunal bypass shorter than the traditional duodenal switch) is often performed as metabolic surgery, and studies on this surgical technique are being actively conducted in Japan. SG with DJB has both effects of stomach restriction and foregut bypass. However, SG with DJB is more disadvantageous compared to SG alone in nutrient absorption after surgery. This is a natural result of bypassing the duodenum and proximal jejunum. Therefore, SG with DJB should not be performed when it is unnecessary, and it should be performed in patients who are expected to show significant improvement in T2DM. However, there is no existing guideline on which patients can receive SG with DJB or SG alone, and there are also no clinical studies on these aspects.

Official Title
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Comparisons of Metabolic Effect of Sleeve Gastrectomy With Duodenojejunal Bypass and Sleeve Gastrectomy (MEDUSA): A Multicenter Randomized Controlled Trial

Conditions
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Bariatric Surgery, Diabetes Mellitus, Type 2, Surgical Procedures, Operative, Asians

Intervention / Treatment
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* Procedure: Duodenojejunal bypass
* Procedure: Sleeve gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age over 18 years BMI equal to or greater than 27.5 kg/m2 T2DM duration ≤ 10 years Using insulin, or HbA1c ≥ 7.0% while taking diabetes medication C-peptide level higher than 1.0 ng/mL Presence of type 2 diabetes fulfilling the following criteria Consent to not become pregnant for at least 1 year after surgery Willingness to provide voluntary informed consent Exclusion Criteria: Presence of uncontrolled severe gastroesophageal reflux (LA classification C or more in esophagogastroduodenoscopy) History of previous metabolic surgery for T2DM History of gastrointestinal surgery, such as gastrectomy or anti-reflux surgery, which may affect the result of metabolic surgery Therapy regimen of more than 3 psychiatric drugs owing to poorly controlled psychiatric disorders Suicidal attempts within the last 12 months Treatment for alcohol and drug abuse within the last 12 months Vulnerability factors (lacking mental capacity, pregnancy or planning of pregnancy, lactation) Unsuitability as per the discretion of the researcher

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: SG group<br>Patients undergoing sleeve gastrectomy | Procedure: Sleeve gastrectomy<br>* Sleeve gastrectomy will be performed using 36-38 Fr bougie. The initial stapling start point will be between 4-6 cm from the pylorus, and the last stapling will be performed at least 1 cm away from His angle. The height of the automatic stapler will be selected based on the researcher's discretion.<br>|
| Experimental: DJB group<br>Patients undergoing duodenojejunal bypass with sleeve gastrectomy | Procedure: Duodenojejunal bypass<br>* Sleeve gastrectomy will be performed in the same manner as in the SG group. DJB will be performed by transection of the duodenum and bypassing 250 cm of the proximal jejunum. The handsewn suture will be used for duodenojejunal anastomosis, and the size of anastomosis will be 1.5 - 2 cm. Single anastomosis will be performed rather than Roux-en-Y fashion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate of type 2 diabetes | HbA1c <6% (or fasting blood glucose [FBG] <100 mg/dL) without using any diabetes medication | 5 years after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate of type 2 diabetes | HbA1c <6% (or fasting blood glucose [FBG] <100 mg/dL) without using any diabetes medication | 1, 3, 10 years after surgery | 
| Partial remission rate of type 2 diabetes | Definition of partial remission of diabetes: HbA1c of 6-6.4% (or FBG of 100-125 mg/dL) without using any diabetes medication | 1, 3, 5, 10 years after surgery | 
| Improvement rate of type 2 diabetes | Definition of improvement of diabetes: Significant reduction in HbA1c (or FBG) level or decrease in the number of diabetic drugs or stoppage of insulin that does not meet the definition of remission. | 1, 3, 5, 10 years after surgery | 
| Hypertension remission rate | Definition of complete remission of hypertension: Blood pressure (BP) <120/80 mmHg without taking BP medication Definition of partial remission of hypertension: BP of 120-140/80-89 mmHg without taking BP medication | 1, 3, 5, 10 years after surgery | 
| Hypertension improvement rate | Definition of improvement of hypertension: Decrease in the number or dose of BP medications or decreased BP while taking medication | 1, 3, 5, 10 years after surgery | 
| Hyperlipidemia remission rate | Definition of remission of hyperlipidemia: Normal lipid profile (triglyceride [TG] <150 mg/dL and low-density lipoprotein [LDL] of 129 mg/dL or less and high-density lipoprotein [HDL] of 40 mg/dL or above) without taking hyperlipidemic drugs | 1, 3, 5, 10 years after surgery | 
| Hyperlipidemia improvement rate | Definition of improvement of hyperlipidemia: Reduced number or dose of hyperlipidemic drugs or improved lipid profile while taking hyperlipidemic drugs | 1, 3, 5, 10 years after surgery | 
| Prevalence of GERD | Acid reflux symptoms and positive endoscopic findings (LA classification A or more) | 1, 3, 5, 10 years after surgery | 
| Trace element deficiency rate (iron, vitamin B12, folate, vitamin B1, vitamin D, copper [Cu], and zinc [Zn]) | Iron deficiency: ferritin <20 ng/mL or iron <50 mcg/dL Vitamin B12 deficiency: <200 pg/mL, vitamin B12 suboptimal: 200 - <400 pg/mL Folate deficiency: <10nmol/L (4.4ng/mL) Vitamin B1 deficiency: <2.36 mcg/dL Vitamin D deficiency: <20 mg/mL, vitamin D insufficiency: 20-<30 ng/mL Cu deficiency: <75 mcg/dL Zn deficiency: <70 mcg/dL in women, < 74 mcg/dL in men | 1, 3, 5, 10 years after surgery | 
| Changes in body weight | kilograms | 1, 3, 5, 10 years after surgery | 
| Changes in body composition | body fat percentage(%), body fat mass (kg), and muscle mass(kg) | 1, 3, 5, 10 years after surgery | 
| Changes in Quality of life | IWQOL-Lite, SF-12 | 1, 3, 5, 10 years after surgery | 
| Early complication rate |  | Early: within 30 days after surgery | 
| Late complication rate |  | Late: later than 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bariatric Surgery, Metabolic Surgery, Diabetes Remission