Effects on Remission of Type 2 Diabetes Mellitus Following Gastric Bypass Alone vs Gastric Bypass Combined With Truncal Vagotomy
VagusSx
1 other identifier
interventional
40
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable diabetes-mellitus-type-2
Started Apr 2026
Typical duration for not_applicable diabetes-mellitus-type-2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 28, 2025
CompletedFirst Posted
Study publicly available on registry
December 11, 2025
CompletedStudy Start
First participant enrolled
April 24, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
April 30, 2026
April 1, 2026
2.6 years
September 28, 2025
April 28, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (26)
Partial remission of type 2 diabetes
12 months postoperatively
Fasting Plasma Glucose
Baseline and up to 12 months postoperatively
Fasting Insulin
Baseline and 12 months postoperatively
Fasting C-Peptide levels
Baseline and 12 months postoperatively
HbA1c
Baseline, 1, 3, 6, and 12 months postoperatively
- +21 more secondary outcomes
Other Outcomes (23)
Postprandial Hormonal and Glucose Response to Mixed-Meal Test
Baseline and 12 months postoperatively
Prevalence of Micronutrient Deficiencies
Baseline, 1, 3, 6, and 12 months postoperatively (selected micronutrients per protocol schedule)
Obstructive Sleep Apnea Score
Baseline and 12 months postoperatively
- +20 more other outcomes
Study Arms (2)
Roux-en-Y Gastric Bypass with Truncal Vagotomy
EXPERIMENTALParticipants 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.
Roux-en-Y Gastric Bypass Alone
ACTIVE COMPARATORParticipants 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.
Interventions
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.
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Diabetes Surgery
Athens, Attica, 11527, Greece
Diabetes Surgery
Athens, Attica, 11527, Greece
Related Publications (2)
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.
PMID: 40864811BACKGROUNDKapralou 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.
PMID: 35835160BACKGROUND
Related 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.
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- General Surgeon, Scientific Associate, First Department of Propaedeutic Surgery, National and Kapodistrian University of Athens
Study Record Dates
First Submitted
September 28, 2025
First Posted
December 11, 2025
Study Start
April 24, 2026
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
December 1, 2028
Last Updated
April 30, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Beginning 3 months after publication of the primary results with no end date.
- 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
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.