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

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

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Surgical Procedures, Operative; Bariatric Surgery; Asians
• Intervention / Treatment: Procedure: Sleeve gastrectomy; Procedure: Duodenojejunal bypass

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Young Suk Park; Phone Number: +82-10-8980-6094; Email: youngsukmd@gmail.com

Study Locations

• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Young Suk Park; Email: youngsukmd@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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
Active Comparator: SG group; Patients undergoing sleeve gastrectomy	Procedure: Sleeve gastrectomy; 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.
Experimental: DJB group; Patients undergoing duodenojejunal bypass with sleeve gastrectomy	Procedure: Duodenojejunal bypass; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Korea University; Ajou University School of Medicine; The Catholic University of Korea; Soonchunhyang University Hospital; The Catholic University of Korea Eunpyeong St. Mary's Hospital; Ewha University Seoul Hospital; Seoul Metropolitan Boramae Hospital
• Investigators: Principal Investigator: Young Suk Park, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Hofso D, Fatima F, Borgeraas H, Birkeland KI, Gulseth HL, Hertel JK, Johnson LK, Lindberg M, Nordstrand N, Cvancarova Smastuen M, Stefanovski D, Svanevik M, Gretland Valderhaug T, Sandbu R, Hjelmesaeth J. Gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (Oseberg): a single-centre, triple-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Dec;7(12):912-924. doi: 10.1016/S2213-8587(19)30344-4. Epub 2019 Oct 31.
• Aminian A, Brethauer SA, Andalib A, Nowacki AS, Jimenez A, Corcelles R, Hanipah ZN, Punchai S, Bhatt DL, Kashyap SR, Burguera B, Lacy AM, Vidal J, Schauer PR. Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes Severity. Ann Surg. 2017 Oct;266(4):650-657. doi: 10.1097/SLA.0000000000002407.
• Brethauer SA, Kim J, el Chaar M, Papasavas P, Eisenberg D, Rogers A, Ballem N, Kligman M, Kothari S; ASMBS Clinical Issues Committee. Standardized outcomes reporting in metabolic and bariatric surgery. Surg Obes Relat Dis. 2015 May-Jun;11(3):489-506. doi: 10.1016/j.soard.2015.02.003. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Anticipated): January 3, 2031
• Study Completion (Anticipated): January 3, 2036

Study Registration Dates

• First Submitted: January 4, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Actual): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Bariatric Surgery; Diabetes Remission; Metabolic Surgery
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: MEDUSA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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