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.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Complete remission of Type 2 Diabetes Mellitus at 12 Months Post-Surgery
研究概览
简要总结
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:
- RYGB alone, or
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 68 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Roux-en-Y Gastric Bypass plus Truncal Vagotomy (Procedure)
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.
干预措施: Roux-en-Y Gastric Bypass (Procedure)
结局指标
主要结局
Complete remission of Type 2 Diabetes Mellitus at 12 Months Post-Surgery
时间窗: 12 months postoperatively
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.
次要结局
- 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)
- Use of Insulin Therapy(Baseline, 1, 3, 6, and 12 months postoperatively)
- Body Weight(Baseline, 1, 3, 6, and 12 months postoperatively)
- Fasting C-Peptide levels(Baseline and 12 months postoperatively)
- HOMA-IR (Insulin Resistance Index)(Baseline and 12 months postoperatively)
- HbA1c(Baseline, 1, 3, 6, and 12 months postoperatively)
- Use of Antidiabetic Medications(Baseline, 1, 3, 6, and 12 months postoperatively)
- Oral Glucose Tolerance Test (OGTT) Indices-plasma glucose measurement(Baseline and 12 months postoperatively)
- Body Mass Index (BMI)(Baseline, 1, 3, 6, and 12 months postoperatively)
- Waist and Hip Circumference(Baseline, 1, 3, 6, and 12 months postoperatively)
- Body Composition(Baseline and 12 months postoperatively)
- Total Cholesterol(Baseline, 1, 3, 6, and 12 months postoperatively)
- HDL Cholesterol(Baseline, 1, 3, 6, and 12 months postoperatively)
- LDL Cholesterol(Baseline, 1, 3, 6, and 12 months postoperatively)
- Triglycerides(Baseline, 1, 3, 6, and 12 months postoperatively)
- C-Reactive Protein (CRP)(Baseline, 1, 3, 6, and 12 months postoperatively)
- Blood Pressure(Baseline, 1, 3, 6, and 12 months postoperatively)
- Change in Use of Lipid-Lowering Medications(Baseline, 1, 3, 6, and 12 months postoperatively)
- Use of Antihypertensive Medications(Baseline, 1, 3, 6, and 12 months postoperatively.)
- Cardiovascular Risk Index (Obesity-Related)(Baseline and 12 months postoperatively)
- Cardiovascular Risk Index (Diabetes-Related)(Baseline and 12 months postoperatively)
- Oral Glucose Tolerance Test (OGTT) Indices-plasma insulin measurement(Baseline and 12 months postoperatively)
- Oral Glucose Tolerance Test (OGTT) Indices-plasma C-peptide levels(Baseline and 12 months postoperatively)
- Discontinuation of Antidiabetic Medications(Baseline, 1, 3, 6, and 12 months postoperatively)
研究者
Athena Kapralou
General Surgeon, Scientific Associate, First Department of Propaedeutic Surgery, National and Kapodistrian University of Athens
University Research Institute for the Study of Genetic & Malignant Disorders in Childhood