Endoscopic Injection of Autologous Fat-Derived Cells (SVF) for Adults With Refractory Gastroesophageal Reflux Disease (GERD). (The GERD-REVIVE Pilot Study) (GERD-REVIVE)

Submucosal Injection of Autologous Stromal Vascular Fraction (SVF) at the Esophagogastric Junction for the Treatment of Gastroesophageal Reflux Disease (GERD): A Single-Arm Pilot Feasibility and Safety Study

The purpose of this pilot clinical study is to evaluate the feasibility and safety of an innovative endoscopic treatment for adults with gastroesophageal reflux disease (GERD) that does not respond adequately to standard medications. The study focuses on the anti-reflux barrier between the esophagus and the stomach, which fails in patients with GERD. Instead of traditional surgery, this study explores a minimally invasive approach: injecting a specialized mixture of the patient's own fat-derived cells-known as the Stromal Vascular Fraction (SVF)-directly into the tissue at the esophagogastric junction during a standard endoscopy. The study is trying to answer two primary questions: Is it clinically feasible and safe to harvest, process, and endoscopically inject autologous SVF cells to support the anti-reflux barrier? Can this cell-based intervention help repair the tissue and improve the mechanical function of the barrier, allowing patients to reduce or completely stop their daily reliance on proton pump inhibitors (PPIs)? By answering these questions in a small group of 15 participants, this pilot trial aims to provide the foundational data necessary to design larger clinical studies in the future.

Study Overview

• Status: Not yet recruiting
• Conditions: GERD (Gastroesophageal Reflux Disease)
• Intervention / Treatment: Procedure: Autologous Stromal Vascular Fraction (SVF) Endoscopic Injection

Detailed Description

This is a prospective, single-arm pilot study involving 15 adult patients. The intervention is performed in a single session and consists of three distinct sequential phases: Adipose Tissue Harvesting - autologous fat is obtained via a mini-subcutaneous liposuction from a suitable donor area under local anesthesia using a specialized tumescent solution. GMP-Compliant Processing (ELEA Method) - the lipoaspirate is processed in a GMP-compliant environment using mechanical activation via a Digital Vortex Mixer at 2000 rpm for 8 minutes. The resulting SVF-rich activated fat fraction is separated from the liquid and oil phases, emulsified through a 2 mm filter, and loaded into an endoscopic injection needle. Endoscopic Delivery - under direct endoscopic visualization, the activated SVF is injected circumferentially into the submucosal plane of the esophagogastric junction (EGJ), distributed across four quadrants (typically 0.5-1 cm above the squamocolumnar junction) to achieve a symmetric deposition cushion.

Schedule of Assessments and Follow-up Timeline: the total study duration for each participant is 12 months, with scheduled clinic or phone follow-up assessments at Months 1, 3, 6, and 12.

Baseline Evaluation: participants undergo a screening assessment including medical history, GERD Health-Related Quality of Life (GERD-HRQL) questionnaire, baseline upper endoscopy (EGD) with EGJ biopsies, high-resolution manometry (HRM) per Chicago v4.0, and 24-hour pH-impedance monitoring per Lyon 2.0 (performed off PPI therapy for at least 7 days).

Month 6 Evaluation: patients undergo a comprehensive objective re-evaluation including a repeat EGD with follow-up EGJ biopsies, HRM, 24-hour pH-impedance monitoring, and GERD-HRQL scoring.

Month 12 Evaluation: final clinical assessment focusing on long-term safety, adverse event reviewing, GERD-HRQL scoring, and medication status tracking (PPI discontinuation or reduction rates).

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ivo Boskoski, Medical degree; Phone Number: 06 3015 6580; Email: ivo.boskoski@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults 18-75 years; actionable GERD per Lyon 2.0 (e.g., AET >6% off therapy; or LA grade B-D, peptic stricture, Barrett's) and compatible symptoms. [2]
• Refractory symptoms on optimized PPIs or PPI-dependent disease where intervention is contemplated. [2]
• HRM excluding major motility disorders (per Chicago v4.0). [21]
• Willing to undergo adipose harvest and autologous SVF therapy within a clinical trial framework.

Exclusion Criteria:

• Hiatal hernia >3 cm or paraesophageal hernia; severe esophagitis with ulcers (grade B or more); Barrett's with dysplasia; strictures; achalasia/EGJOO/spastic disorders. [2,21]
• Coagulopathy, uncontrolled cardiopulmonary disease, pregnancy/lactation.
• Active infection/malignancy significant for increased risk, at PI discretion.
• Prior fundoplication or magnetic sphincter augmentation within 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adults 18-75 years with actionable GERD per Lyon 2.0, refractory or PPI-dependent; motility disorder; Eligible participants will undergo a single session of endoscopic submucosal injection of autologous, mechanically activated Stromal Vascular Fraction (SVF) at the esophagogastric junction (EGJ). The procedure consists of: Autologous adipose tissue harvesting via a mini-subcutaneous liposuction. GMP-compliant mechanical processing of the lipoaspirate using the ELEA method (vortex mixing at 2000 rpm for 8 minutes and emulsification through a 2 mm filter) to isolate the SVF-rich activated fat fraction. Direct endoscopic delivery via circumferential injections distributed across four quadrants in the submucosal plane of the EGJ (typically 0.5-1 cm above the squamocolumnar junction). Follow-up assessments will be conducted up to 12 months to evaluate safety, clinical response, and anti-reflux barrier metrics.

Procedure: Autologous Stromal Vascular Fraction (SVF) Endoscopic Injection; This intervention is characterized by the localized, circumferential delivery of a point-of-care, autologous cell mixture derived from adipose tissue, distinguished by the following specific methodological parameters: Mechanical Processing (ELEA Method) - unlike chemical enzymatic digestion or standard centrifugation, the harvested fat is processed using purely mechanical activation via a Digital Vortex Mixer at 2000 rpm for exactly 8 minutes to separate the Stromal Vascular Fraction (SVF)-rich activated fat fraction. Emulsification - the isolated activated fat fraction is emulsified by mechanical passage through a dedicated 2 mm filter before being loaded into a 19-gauge endoscopic injection needle. Anatomical Site and Delivery - the cell-rich cushion is injected submucosally and symmetrically across four quadrants at the esophagogastric junction (EGJ), precisely 0.5 to 1 cm above the squamocolumnar junction, to physically and biologically augment the anti-reflux barrier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of autologous Stromal Vascular Fraction (SVF) harvesting, processing, and endoscopic delivery	The proportion of participants who successfully undergo the entire procedural workflow without major protocol deviations. This includes successful mini-subcutaneous adipose tissue harvesting, GMP-compliant mechanical processing via the ELEA method, and symmetric endoscopic submucosal injection at the esophagogastric junction.	day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of procedure- and product-related adverse events (AEs) and serious adverse events (SAEs)	Safety will be assessed by recording the frequency, severity, and cumulative incidence of all local and systemic adverse events. This includes specific monitoring for bleeding, perforation, infection, chest pain, dysphagia, stricture formation, mediastinitis, ectopic nodules, or neoplastic changes at the esophagogastric junction.	Up to 12 months post-procedure.

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Gastroesophageal Reflux; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy
• Other Study ID Numbers: 14201

Drug and device information, study documents

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