Effects on Remission of Type 2 Diabetes Mellitus Following Gastric Bypass Alone vs Gastric Bypass Combined With Truncal Vagotomy (VagusSx)

Effects on Remission of Type 2 Diabetes Mellitus Following Roux-en-Y Gastric Bypass Alone vs Roux-en-Y Gastric Bypass Combined With Truncal Vagotomy: A Triple-Blind Randomized Controlled Trial.

This randomized, triple-blind clinical trial investigates whether adding truncal vagotomy to Roux-en-Y gastric bypass (RYGB) enhances remission of type 2 diabetes mellitus (T2DM) in patients with obesity. The study explores whether modulation of vagal signaling provides superior metabolic outcomes compared to standard RYGB alone.

Background:

RYGB is a proven metabolic procedure capable of inducing diabetes remission; however, the mechanisms remain incompletely defined. Emerging evidence supports a duodenum-centered neurohormonal model suggesting that amplified digestion-driven by vagal and hormonal hyperstimulation-plays a key role in the development of insulin resistance. The vagus nerve regulates pancreatic and biliary secretion, as well as gut hormone release. By combining truncal vagotomy with RYGB, the study aims to attenuate vagal overactivation and evaluate its impact on glucose homeostasis and hormonal adaptation.

Design:

Eligible adults (18-65 years) with BMI ≥30 kg/m² and confirmed T2DM (HbA1c ≥6.5%, or on antidiabetic therapy with HbA1c ≥6.1%) will be randomized to:

1. RYGB alone, or
2. RYGB with truncal vagotomy. Participants, postoperative staff, and assessors will remain blinded to allocation.

Primary Outcome:

Remission of T2DM at 12 months postoperatively, defined as fasting plasma glucose <100 mg/dL and HbA1c <6.0% without antidiabetic medication for at least one year.

Secondary Outcomes:

Changes in HbA1c, fasting glucose, insulin, C-peptide, OGTT-derived indices, GLP-1, CCK, PYY, GLP-2, oxyntomodulin responses, HOMA-IR, body composition, cardiovascular risk markers, medication use, and quality-of-life parameters. Surgical metrics include hospital stay, readmissions, complications, gastrointestinal symptoms, nutritional deficiencies, and bone density changes.

Follow-Up:

Assessments occur preoperatively and at 1, 3, 6, and 12 months after surgery.

Significance:

The VagusSx Trial tests whether targeted vagal and duodenal pathway interruption can improve glycemic control beyond weight loss alone, offering a novel, physiology-based strategy for durable diabetes remission.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Procedure: Roux-en-Y Gastric Bypass plus Truncal Vagotomy; Procedure: Roux-en-Y Gastric Bypass

Detailed Description

Detailed Description

This randomized, triple-blind, controlled clinical trial evaluates the metabolic impact of adding truncal vagotomy to standard Roux-en-Y gastric bypass (RYGB) in adults with obesity and type 2 diabetes mellitus (T2DM). The trial, titled VagusSx, investigates whether targeted interruption of vagal signaling augments diabetes remission beyond the effects of caloric restriction and weight loss alone.

Scientific Background and Rationale

RYGB has been established as an effective metabolic surgery leading to remission of T2DM in a significant proportion of patients. However, the exact mechanisms remain incompletely understood. Increasing evidence supports a duodenum-centered neurohormonal model in which amplified digestion-driven by chronic vagal and enteroendocrine hyperstimulation-promotes insulin resistance. The vagus nerve regulates biliopancreatic secretion, gastric motility, and the release of hormones such as cholecystokinin (CCK) and secretin. Continuous exposure to high-fat, high-glycemic diets may cause persistent vagal activation, exaggerated hormonal secretion, and enhanced nutrient absorption, ultimately contributing to β-cell stress and insulin resistance.

Truncal vagotomy is hypothesized to attenuate this hyperactivation, reducing biliopancreatic output and digestive efficiency, thereby improving glucose homeostasis and insulin sensitivity. When combined with RYGB-which excludes the duodenal mucosa from nutrient contact and enhances distal gut hormone signaling-the dual intervention may provide synergistic effects through both neural and hormonal pathways.

Study Design

This is a prospective, randomized (1:1), triple-blind clinical trial with two parallel arms:

Standard RYGB (control group)

RYGB plus truncal vagotomy (intervention group)

Participants, postoperative care staff, and assessors remain blinded to allocation. Randomization is performed via concealed envelopes using computer-generated sequences.

Eligibility

Inclusion criteria: adults aged 18-65 years, BMI ≥30 kg/m², confirmed T2DM with HbA1c ≥ 6.5% or use of antidiabetic medication with HbA1c ≥ 6.1%, and Advanced DiaRem Score > 5.

Key exclusion criteria: prior bariatric or major abdominal surgery, type 1 diabetes, chronic corticosteroid use, major psychiatric or systemic disease, or substance abuse.

Interventions

All surgeries are performed laparoscopically by the same surgical team.

Roux-en-Y gastric bypass (RYGB): creation of a small gastric pouch, gastrojejunostomy, and jejunojejunostomy (proximal intestinal bypass).

Truncal vagotomy: complete division of anterior and posterior vagal trunks at the distal esophagus prior to gastric pouch creation.

Standardized perioperative and nutritional management is applied to both groups.

Assessments and Follow-Up

Participants are evaluated at baseline (preoperative), and at 1, 3, 6, and 12 months postoperatively.

Data are collected by a multidisciplinary team (surgery, endocrinology, dietetics, psychology) using standardized laboratory, imaging, and validated questionnaires.

Primary Outcome

Remission of T2DM at 12 months, defined as fasting plasma glucose < 100 mg/dL and HbA1c < 6.0% without antidiabetic therapy for ≥12 months.

Key Secondary Outcomes

Glycemic and hormonal parameters: HbA1c, fasting glucose, insulin, C-peptide, OGTT-derived indices (insulin sensitivity, β-cell responsiveness, disposition index), and hormonal responses (GLP-1, CCK, PYY, GLP-2, oxyntomodulin).

Body composition and anthropometry: weight, BMI, waist/hip ratio, fat mass, lean mass.

Cardiometabolic risk markers: lipid profile, blood pressure, CRP, ASCVD and SCORE2-Diabetes risk indices.

Bone status: bone mineral density by DEXA.

Nutritional status: micronutrient levels (vitamins A, D, E, K, B1, B12, folate, iron, zinc, copper, calcium, magnesium, phosphorus) and prevalence of deficiencies.

Medication use: discontinuation or reduction of antidiabetic, antihypertensive, and lipid-lowering therapies.

Surgical metrics: length of stay, readmissions, early and late complications (graded by Dindo classification), gastrointestinal symptoms, dumping syndrome, and hypoglycemia episodes.

Dietary behavior: changes in food frequency, tolerance, craving, and binge-eating scales.

Physical activity: objectively measured and self-reported activity (IPAQ).

Psychosocial outcomes: treatment satisfaction, diabetes-related symptoms, and psychological well-being.

Data Management and Analysis

All data are recorded in electronic case-report forms and stored in a secure database. Continuous variables will be analyzed using repeated-measures ANOVA or mixed models. Categorical data will be compared with χ² or Fisher's exact tests. Statistical significance is set at p < 0.05. Intention-to-treat and per-protocol analyses will be performed.

Ethical Considerations

The trial adheres to the Declaration of Helsinki, Good Clinical Practice (GCP) standards, and COPE ethical guidelines. Written informed consent is obtained from all participants. The study protocol has received institutional ethics approval and is registered at ClinicalTrials.gov.

Significance

The VagusSx trial introduces a novel physiologic concept: neural-hormonal modulation of digestion as a therapeutic target in diabetes surgery. By interrupting vagal and proximal intestinal signaling, the study aims to test whether this combined intervention promotes durable diabetes remission beyond the effects of caloric restriction, potentially reshaping the mechanistic understanding and future direction of metabolic surgery.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Athena N Kapralou, MD, PhD; Phone Number: +306945750599; Email: athinakapralou@gmail.com

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • Recruiting
      • Diabetes Surgery
      • Contact: Athena N Kapralou, MD, PhD; Phone Number: +306945750599; Email: athinakapralou@gmail.com
    • Athens, Attica, Greece, 11527
      • Not yet recruiting
      • Diabetes Surgery
      • Contact: Athena Kapralou, MD, PhD; Phone Number: +30 6945750599; Email: athinakapralou@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI ≥ 30 kg/m²
• Age: 18-68 years

• Confirmed type 2 diabetes mellitus with:

  • HbA1c ≥ 6.5%, or
  • HbA1c ≥ 6.1% and the use of antidiabetic medication
• Advanced-DiaRem Score > 5* * Advanced-DiaRem Score: a validated scoring system predicting diabetes remission after bariatric surgery.

Exclusion Criteria:

• Previous bariatric surgery or major abdominal surgery (e.g., enterectomy, gastrectomy, colectomy, hepatectomy, partial or total pancreatectomy)
• Major, uncompensated health problems (major psychiatric, endocrine, cardiac, pulmonary, hepatic, or renal disorder; cancer; or other conditions with increased risk of complications)

• Use of corticosteroids (glucocorticoids):

  • Chronic corticosteroid use for > 3 months within the last year, or
  • Corticosteroid therapy within the last 3 months
• Type 1 diabetes mellitus
• Alcohol or drug addiction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roux-en-Y Gastric Bypass with Truncal Vagotomy; Participants in this arm will undergo a standard laparoscopic Roux-en-Y gastric bypass (RYGB) procedure combined with bilateral truncal vagotomy. The operation includes creation of a small gastric pouch completely separated from the remnant stomach, gastrojejunostomy to the alimentary limb, and a jejunojejunostomy to restore intestinal continuity, resulting in proximal intestinal bypass of the duodenum and proximal jejunum. Truncal vagotomy is performed by dividing both anterior and posterior vagal trunks at the lower esophagus to reduce vagally mediated biliopancreatic secretion and neurohormonal stimulation of digestion. This combined procedure aims to assess whether dual interruption of vagal and duodenal signaling enhances the metabolic and glycemic benefits of gastric bypass, promoting durable remission of type 2 diabetes mellitus.	Procedure: Roux-en-Y Gastric Bypass plus Truncal Vagotomy; Laparoscopic Roux-en-Y gastric bypass performed according to protocol, including creation of a small gastric pouch, gastrojejunostomy, and jejunojejunostomy. In addition, bilateral truncal vagotomy is performed at the distal esophagus, dividing both anterior and posterior vagal trunks to reduce vagal stimulation of the gastrointestinal tract. The combined procedure aims to assess whether vagotomy enhances type 2 diabetes mellitus remission beyond the effect of gastric bypass alone.
Active Comparator: Roux-en-Y Gastric Bypass Alone; Participants in this arm will undergo a standard laparoscopic Roux-en-Y gastric bypass (RYGB) procedure without vagotomy. The surgery includes creation of a small, completely separated gastric pouch, a gastrojejunostomy to the alimentary limb, and a jejunojejunostomy approximately 100-150 cm distal to the ligament of Treitz, resulting in a proximal intestinal bypass of the duodenum and proximal jejunum. This configuration limits nutrient exposure to the upper gut, thereby inducing metabolic changes known to improve glycemic control and weight reduction. The procedure follows established bariatric surgical principles and serves as the control arm to evaluate the additive effect of truncal vagotomy on glucose homeostasis, gut hormone secretion, and remission of type 2 diabetes mellitus.	Procedure: Roux-en-Y Gastric Bypass; Laparoscopic Roux-en-Y gastric bypass performed according to protocol, including creation of a small gastric pouch, gastrojejunostomy, and jejunojejunostomy. No vagotomy is performed. This serves as the active comparator to evaluate the independent effect of adding truncal vagotomy on type 2 diabetes mellitus remission.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission of Type 2 Diabetes Mellitus at 12 Months Post-Surgery	Complete remission of type 2 diabetes will be defined as fasting plasma glucose <100 mg/dL and HbA1c <6.0%, maintained without the use of any antidiabetic medications for at least one year following surgery.	12 months postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial remission of type 2 diabetes	Partial remission will be defined as HbA1c < 6.5% and fasting plasma glucose between 100-125 mg/dL, maintained without the use of any antidiabetic medications for at least one year following surgery.	12 months postoperatively
Fasting Plasma Glucose	Change in fasting plasma glucose levels will be measured at each follow-up visit (1, 3, 6, and 12 months).	Baseline and up to 12 months postoperatively
Fasting Insulin	Change in fasting insulin levels will be assessed at baseline (pre-surgery) and at 12 months after surgery.	Baseline and 12 months postoperatively
Fasting C-Peptide levels	Change in fasting C-peptide levels will be assessed at baseline (pre-surgery) and at 12 months postoperatively.	Baseline and 12 months postoperatively
HbA1c	Change in HbA1c (%) from baseline across follow-up visits.	Baseline, 1, 3, 6, and 12 months postoperatively
Oral Glucose Tolerance Test (OGTT) Indices-plasma glucose measurement	After an overnight fast, participants will ingest 75 g of glucose orally. Blood samples will be collected at baseline (fasting) and at regular time intervals over a two-hour period, post-pradially to measure plasma glucose, insulin, and C-peptide.	Baseline and 12 months postoperatively
HOMA-IR (Insulin Resistance Index)	The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) will be calculated using fasting plasma glucose and fasting insulin levels, according to the following formula: HOMA-IR=Fasting glucose (mg/dL)×0.0555×Fasting insulin (mU/L)/22.5	Baseline and 12 months postoperatively
Use of Antidiabetic Medications	Change in the number of antidiabetic medications prescribed per patient compared with baseline. Each active oral or injectable non-insulin agent will be counted as one medication. A decrease in the number of medications will be considered an indicator of improved glycemic control. Unit of Measure: Number of medications per participant	Baseline, 1, 3, 6, and 12 months postoperatively
Use of Insulin Therapy	Change in insulin therapy status at each follow-up visit, expressed as the proportion of participants achieving: Complete discontinuation of insulin therapy, ≥50% reduction in daily insulin dose, or No change / continued insulin requirement. The primary reported measure will be the percentage of participants discontinuing insulin therapy, with additional categorical data on dose reduction and continuation summarized descriptively. Unit of Measure: Percentage of participants (%)	Baseline, 1, 3, 6, and 12 months postoperatively
Body Weight	Change in body weight (kg) from baseline at each follow-up visit, measured under standardized conditions.	Baseline, 1, 3, 6, and 12 months postoperatively
Body Mass Index (BMI)	Change in BMI (kg/m²) calculated from measured weight and height at each visit.	Baseline, 1, 3, 6, and 12 months postoperatively
Waist and Hip Circumference	Change in waist and hip circumference (cm) measured with a flexible tape at standardized anatomical landmarks; waist-to-hip ratio will also be derived.	Baseline, 1, 3, 6, and 12 months postoperatively
Body Composition	Change in body fat percentage (% body fat) from baseline to 12 months postoperatively.	Baseline and 12 months postoperatively
Total Cholesterol	Change in fasting total cholesterol (mg/dL) measured by standard enzymatic methods.	Baseline, 1, 3, 6, and 12 months postoperatively
HDL Cholesterol	Change in fasting high-density lipoprotein cholesterol (mg/dL).	Baseline, 1, 3, 6, and 12 months postoperatively
LDL Cholesterol	Change in fasting low-density lipoprotein cholesterol (mg/dL).	Baseline, 1, 3, 6, and 12 months postoperatively
Triglycerides	Change in fasting triglyceride levels (mg/dL).	Baseline, 1, 3, 6, and 12 months postoperatively
C-Reactive Protein (CRP)	Change in high-sensitivity C-reactive protein (mg/L) as a marker of systemic inflammation.	Baseline, 1, 3, 6, and 12 months postoperatively
Blood Pressure	Change in systolic and diastolic blood pressure (mmHg).	Baseline, 1, 3, 6, and 12 months postoperatively
Change in Use of Lipid-Lowering Medications	Change in the proportion of participants using lipid-lowering medications compared to baseline. Medication use status (continued, reduced dose, or discontinued) will be assessed at each postoperative visit.	Baseline, 1, 3, 6, and 12 months postoperatively
Use of Antihypertensive Medications	Change in the number and classes of antihypertensive drugs prescribed.	Baseline, 1, 3, 6, and 12 months postoperatively.
Cardiovascular Risk Index (Obesity-Related)	Change in obesity-related cardiovascular risk, assessed using the ASCVD (Atherosclerotic Cardiovascular Disease) Risk Score developed by the American College of Cardiology. Calculation will be performed using the official online tool: https://tools.acc.org/ascvd-risk-estimator-plus/#!/calculate/estimate/.	Baseline and 12 months postoperatively
Cardiovascular Risk Index (Diabetes-Related)	Change in cardiovascular risk related to diabetes, assessed using the SCORE2-Diabetes risk prediction model, developed, calibrated, and validated by the European Society of Cardiology (ESC). Calculation will be performed through the ESC online tool: https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Risk-assessment/esc-cvd-risk-calculation-app.	Baseline and 12 months postoperatively
Oral Glucose Tolerance Test (OGTT) Indices-plasma insulin measurement	After an overnight fast, participants will ingest 75 g of glucose orally. Blood samples will be collected at baseline (fasting) and at regular time intervals over a two-hour period, post-pradially to measure plasma insulin.	Baseline and 12 months postoperatively
Oral Glucose Tolerance Test (OGTT) Indices-plasma C-peptide levels	After an overnight fast, participants will ingest 75 g of glucose orally. Blood samples will be collected at baseline (fasting) and at regular time intervals over a two-hour period, post-pradially to measure plasma C-peptide.	Baseline and 12 months postoperatively
Discontinuation of Antidiabetic Medications	Proportion of participants who discontinue all antidiabetic medications (excluding insulin) following surgery while maintaining normoglycemia. Unit of Measure: Percentage of participants (%)	Baseline, 1, 3, 6, and 12 months postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial Hormonal and Glucose Response to Mixed-Meal Test	After a 12-hour overnight fast, participants will undergo a standardized mixed-meal test. The test meal (800 kcal total) consists of a solid portion (one egg, two slices of white bread, and 5 g margarine; ~250 kcal) and a liquid portion (200 mL cream with 2 teaspoons chocolate powder; ~550 kcal), consumed within 5 minutes. Blood samples will be collected at baseline (fasting) and at regular time intervals over a three-hour period, post-pradially. Plasma concentrations of glucose, insulin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucagon-like peptide-2 (GLP-2), and oxyntomodulin will be measured to evaluate the postprandial metabolic and hormonal response.	Baseline and 12 months postoperatively
Prevalence of Micronutrient Deficiencies	Proportion of participants presenting with one or more micronutrient deficiencies. Deficiencies will be defined according to standard laboratory reference ranges for each micronutrient (e.g., vitamin B12, folate, vitamin D, iron, ferritin, zinc, copper, vitamins A, E). Blood samples will be obtained per protocol at baseline and follow-up visits (specific micronutrients assessed at 3, 6, or 12 months, as indicated)	Baseline, 1, 3, 6, and 12 months postoperatively (selected micronutrients per protocol schedule)
Obstructive Sleep Apnea Score	Change in obstructive sleep apnea risk assessed using the STOP-Bang questionnaire (http://www.stopbang.ca/osa/screening.php).	Baseline and 12 months postoperatively
Early Postoperative Complications	Evaluation of early postoperative surgical complications graded according to the Clavien-Dindo classification.	Up to 6 weeks postoperatively
Late Postoperative Complications	Evaluation of late postoperative surgical complications, graded according to the Clavien-Dindo classification.	Beyond 6 weeks postoperatively
Length of Hospital Stay	Duration of initial postoperative hospitalization, expressed in calendar days from the date of surgery (Day 0) to the date of discharge. Both mean and median length of stay, along with interquartile ranges, will be reported. Prolonged hospitalizations related to postoperative complications will also be recorded and analyzed separately. Unit of Measure: Days	Index hospitalization (from day of surgery until discharge)
Unplanned Hospital Readmissions	Incidence of unplanned hospital readmissions related to the index surgical procedure. Readmissions are defined as any unscheduled overnight hospital stay following discharge, excluding planned follow-up or elective admissions. Both early (≤30 days) and late (>30 days to 12 months) readmissions will be recorded, with cause and timing documented.	Within 30 days and up to 12 months postoperatively
Surgery-Related Events	Recording and classification of any surgical events directly or indirectly related to the operative procedure. This includes intraoperative events (e.g., bleeding, injury to adjacent organs), early postoperative events (e.g., anastomotic leak, wound infection), and late complications (e.g., stricture, internal hernia). Events will be documented and categorized according to their timing and clinical relevance.	From the day of surgery up to 12 months postoperatively
Medical Events Related to Surgery	Recording of medical conditions that arise directly or indirectly in association with the surgical intervention. This includes events such as pulmonary complications (e.g., pneumonia, atelectasis), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism), cardiovascular complications (e.g., arrhythmias, myocardial infarction), or metabolic disturbances (e.g., electrolyte imbalances, malnutrition). All events will be documented, classified, and analyzed in relation to their potential link to the surgical procedure.	From the day of surgery up to 12 months postoperatively
Diabetes-Related Complications	Occurrence of acute and chronic complications directly associated with type 2 diabetes mellitus. This includes hypoglycemic episodes, diabetic ketoacidosis, hyperosmolar states, infections with impaired wound healing, and progression or new onset of microvascular (retinopathy, nephropathy, neuropathy) or macrovascular complications. All events will be systematically recorded, graded, and analyzed in relation to the postoperative course.	From the day of surgery up to 12 months postoperatively
Hypoglycemia Episodes	ypoglycemia will be assessed based on patient-reported symptoms, using the 11 most frequent clinical manifestations described in the Edinburgh Hypoglycemia Scale. These include: Autonomic Nervous System Symptoms: sweating, palpitations, tremor, hunger Neuroglycopenic Symptoms: confusion, drowsiness, abnormal behavior, speech difficulty, incoherence General Malaise: headache, nausea Episodes will be systematically captured and evaluated with the modified Clarke Hypoglycemia Questionnaire, adapted for patients with type 2 diabetes mellitus. The scoring range is 2-46 points, with higher scores reflecting greater hypoglycemia risk and severity.	From baseline through 12 months postoperatively
Dumping Syndrome Assessment	The presence and severity of dumping syndrome will be evaluated using two validated scoring systems: Sigstad's Score - Traditionally applied in peptic ulcer surgery, bariatric surgery, and upper gastrointestinal surgery. It is primarily used for the identification of early dumping syndrome. Arts Dumping Score Questionnaire - Used to differentiate early from late dumping syndrome and to quantify the severity of symptoms. These tools will enable systematic identification of clinically significant dumping symptoms and monitoring of their progression over time.	Baseline, 1, 3, 6, and 12 months postoperatively
Gastrointestinal Symptoms	Gastrointestinal symptoms will be assessed using the Gastrointestinal Symptom Rating Scale (GSRS), as adapted for gastric bypass patients. This validated questionnaire evaluates the frequency and severity of common gastrointestinal complaints, providing a standardized measure of postoperative changes in digestive function.	Baseline, 1, 3, 6, and 12 months postoperatively
Screening for Micronutrient Deficiencies	Patients will undergo systematic preoperative and postoperative screening of vitamin and mineral levels in order to identify and correct deficiencies, in accordance with the American Society for Metabolic and Bariatric Surgery (ASMBS) guidelines. This includes assessment of key micronutrients such as fat- and water-soluble vitamins (A, D, E, K, B12, folate), iron, calcium, magnesium, zinc, and phosphorus.	Baseline, 3, 6, and 12 months postoperatively (frequency depending on the nutrient, per ASMBS guidelines and the study protocol
Bone Mineral Density	Bone mineral density will be assessed using dual-energy X-ray absorptiometry (DEXA). The outcome will evaluate changes in bone density to monitor potential skeletal effects of surgery.	Baseline and 12 months postoperatively
Meal Frequency and Food Intake Patterns (Food Frequency Questionnaire - FFQ)	Change in dietary intake patterns assessed using the Food Frequency Questionnaire (FFQ). The FFQ evaluates the frequency, type, and portion of foods consumed to identify shifts in caloric intake, macronutrient composition, and eating habits following surgery. Unit of Measure: FFQ score (frequency scale)	Baseline and 12 months postoperatively
Self-Reported Physical Activity	Self-reported physical activity will be assessed using the short version of the International Physical Activity Questionnaire (IPAQ-short form).	Baseline and 12 months postoperatively
Diabetes Treatment Satisfaction	Treatment satisfaction will be assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ). The instrument includes 8 items that measure patients' overall satisfaction with their diabetes therapy, perceived convenience, understanding of treatment, and willingness to continue. For the purposes of this study, the questionnaire has been adapted to reflect surgical treatment of diabetes rather than pharmacological management.	Baseline and 12 months postoperatively
Diabetes-Related Symptoms	The Type 2 Diabetes Symptom Checklist (DSC-T2) will be used to evaluate the severity and frequency of diabetes-related symptoms.	Baseline and 12 months postoperatively
Psychological Distress	Psychological distress and depressive symptoms will be assessed using the Beck Depression Inventory-II (BDI-II).	Baseline and 12 months postoperatively.
Food Tolerance (Food Tolerance Questionnaire - FTQ)	Change in food tolerance and gastrointestinal comfort assessed by the Food Tolerance Questionnaire (FTQ). Participants rate their ability to tolerate different food textures and types (e.g., meats, dairy, fibrous foods) after surgery. Unit of Measure: FTQ total score.	Baseline and 12 months postoperatively
Food Craving and Motivation (Food Craving Questionnaire - FCQ)	Assessment of craving intensity and motivational drive toward specific foods using the Food Craving Questionnaire (FCQ). The FCQ evaluates both the frequency and emotional triggers associated with cravings after metabolic surgery. Unit of Measure: FCQ total score	Baseline and 12 months postoperatively
Binge Eating Behavior (Binge Eating Scale - BES)	Evaluation of binge eating behavior using the Binge Eating Scale (BES). The BES assesses the presence and severity of binge eating episodes and emotional eating patterns, with higher scores indicating more severe binge behavior. Unit of Measure: BES score (points)	Baseline and 12 months postoperatively

Collaborators and Investigators

• Sponsor: University Research Institute for the Study of Genetic & Malignant Disorders in Childhood
• Collaborators: National and Kapodistrian University of Athens

Publications and helpful links

General Publications

• Kapralou AN, Yapijakis C, Chrousos GP. The Duodenum-Centered Neurohormonal Hypothesis of Type 2 Diabetes: A Mechanistic Review and Therapeutic Perspective. Curr Issues Mol Biol. 2025 Aug 14;47(8):657. doi: 10.3390/cimb47080657.
• Kapralou AN, Chrousos GP. Metabolic effects of truncal vagotomy when combined with bariatric-metabolic surgery. Metabolism. 2022 Oct;135:155263. doi: 10.1016/j.metabol.2022.155263. Epub 2022 Jul 11.

Helpful Links

• Detailed information about the VagusSx Clinical Trial evaluating the effects of Roux-en-Y Gastric Bypass with or without Truncal Vagotomy on remission of Type 2 Diabetes Mellitus in patients with obesity.
• Peer-reviewed article by our research team (who also registered this clinical trial) exploring the metabolic effects of truncal vagotomy when combined with gastric bypass, providing mechanistic support for this novel surgical strategy in type 2 diabetes.
• Official website of the A' Department of Propaedeutic Surgery, School of Medicine, National and Kapodistrian University of Athens, based at Hippocration General Hospital of Athens - the site where the clinical trial will be conducted.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 28, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Actual): December 11, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Obesity; GLP-1; Insulin Resistance; Hyperglycemia; Type 2 diabetes mellitus; Bariatric Surgery; Gastric Bypass; Gut Hormones; Vagotomy; Diabetes Surgery
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Hyperglycemia; Insulin Resistance; Therapeutics; Surgical Procedures, Operative; Digestive System Surgical Procedures; Neurosurgical Procedures; Anastomosis, Surgical; Bariatric Surgery; Bariatrics; Obesity Management; Gastroenterostomy; Denervation; Vagotomy; Parasympathectomy; Autonomic Denervation; Gastric Bypass; Vagotomy, Truncal
• Other Study ID Numbers: HippokrationHosp89/14-07-2025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Yes. Individual participant data (IPD) that underlie the results reported in future publications will be shared, including de-identified datasets of baseline characteristics, perioperative data, and postoperative outcomes (glycemic indices, weight, laboratory results, complications, and follow-up measures). A data dictionary describing all variables will also be provided to allow full interpretation. Data will be available to qualified researchers upon reasonable request and with approval from the coordinating center at Hippokration University Hospital.
• IPD Sharing Time Frame: Beginning 3 months after publication of the primary results with no end date.

IPD Sharing Access Criteria

De-identified individual participant data (IPD) and supporting documents (Study Protocol, Statistical Analysis Plan, Informed Consent Form) will be available to qualified researchers affiliated with Hippokration University Hospital. Access will be granted for scientifically valid analyses that are consistent with the objectives of the VagusSx trial, particularly in the fields of diabetes, obesity, metabolic surgery, and related endocrine or cardiovascular outcomes.

Requests must include a research proposal outlining study objectives, statistical methods, and a data management plan. All requests will be reviewed by the VagusSx Trial Steering Committee at Hippokration University Hospital to ensure scientific merit, ethical compliance, and alignment with participant consent.

Approved researchers will be required to sign a data sharing agreement to protect confidentiality and limit use of the data to the approved project. Data will be provided in ele

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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