PROJECT SUMMARY Conventional vertical sleeve gastrectomy (cVSG) accounts for approximately 60% of all bariatric surgery procedures. Its popularity is attributable to procedural simplicity, low complications, durable weight loss and significant improvement of obesity-related comorbidities. However, numerous studies have found that the cVSG is associated with new-onset gastroesophageal reflux disease (GERD) and persistence or worsening of pre-existing GERD. Chronic GERD is associated with increased risk for Barrett’s esophagus and esophageal cancer. Hence, it is imperative to develop strategies to minimize GERD associated with the cVSG. The pathophysiology cVSG-associated GERD is attributable to its surgical technique. First, the patients evaluated for bariatric surgery are often found to have a defective antireflux barrier (ARB) and hiatal hernia, which increase the risk of GERD. Second, the cVSG removes the entire gastric fundus resulting in 1) higher intragastric pressure which is conducive to reflux, 2) disrupts gastric sling fibers leading to altered lower esophageal sphincter function, and 3) disrupts the gastric cardia leading to loss of the gastroesophageal flap valve (GEFV). The current project will test a modified VSG (mVSG) which will preserve the gastric sling fibers, anchor the cardia to the distal esophagus, and recreate the GEFV. INNOVATE-VSG is a randomized single- blind clinical trial with a 12-month follow-up. A total of 40 subjects with BMI 30-50 kg/m2 and GERD, meeting eligibility for bariatric surgery, will be randomly assigned in 1:1 ratio to the conventional VSG (cVSG) or the mVSG at two academic sites. Aim 1. to determine whether mVSG, in comparison to cVSG, will be associated with lower acid exposure time (AET, measured by the Bravo pH test) at 12 months. Aim 2. To elucidate the mechanistic basis for Aim 1, we will perform following tests, before and at 12 months post-surgery: 1) High resolution esophageal manometry (HREM) to determine the LES and intragastric pressure. We expect higher LES pressure and lower intragastric pressure in patients with mVSG vs cVSG. 2) EndoFLIP testing to examine changes in compliance of the LES. We expect lower LES compliance in patients with mVSG vs cVSG. 3) Measure the length of the gastroesophageal flap valve (GEFV) on the retroflex view during endoscopic exam. We expect that GEFV will be present after mVSG vs absent after cVSG. Aim 3. Examine the impact of GERD on quality of life (QoL) with two validated rating scales – GERD-HRQL and SF-36. We hypothesize mVSG patients will have superior QoL compared to cVSG patients at 12 months. Additionally, we examine for the presence of sling fibers in the resected stomach specimens. We expect to see sling fibers to be present in the cVSG specimens but not in the mVSG specimens. We believe that the mVSG will lead to improvement of pre- existing GERD along with improved quality of life for patients with obesity. The study findings have the potential to ...