NCT07022912

PPI Refractory - GERD Mechanisms in Systemic Sclerosis

Objective Assessment of Gastrointestinal Involvement in Patients With Systemic Sclerosis and Gastroesophageal Reflux Symptoms Refractory to Proton Pump Inhibitors.

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 147 (estimated)
• Sponsor: Hospital Universitari Vall d'Hebron Research Institute · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

The goal of this observational study is to learn about the mechanisms of gastroesophageal reflux disease (GERD) in patients with systemic sclerosis (SSc) who continue to experience reflux symptoms despite treatment with proton pump inhibitors (PPIs). The main question it aims to answer is: What are the underlying gastrointestinal mechanisms contributing to PPI-refractory reflux symptoms in patients with SSc? Participants with a confirmed diagnosis of SSc and persistent reflux symptoms despite PPI therapy will undergo standard-of-care diagnostic tests, including high-resolution esophageal manometry and pH-impedance monitoring. Clinical data and test results will be collected and analyzed to identify patterns of motility dysfunction and reflux characteristics associated with refractory symptoms.

Detailed description

Background: Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal manifestations in patients with systemic sclerosis (SSc). However, a significant proportion of these patients experience symptoms that are refractory to treatment with proton pump inhibitors (PPIs), suggesting the involvement of underlying pathophysiological mechanisms that are not yet fully defined. Motor dysfunction in other segments of the gastrointestinal tract may contribute to this refractoriness, but studies addressing this in the SSc population have been limited. Currently, there are no personalized diagnostic algorithms that integrate symptoms, objective motility findings, and clinical characteristics in patients with SSc and GERD. Our goal is to identify the mechanisms associated with the severity of PPI-refractory GERD in SSc and to develop a practical and cost-effective diagnostic model based on objective data to enable personalized medicine. Hypothesis: PPI-refractory GERD in patients with systemic sclerosis can be assessed more sensitively and accurately through objective evaluation of motility across different gastrointestinal organs. Objective: To assess the pathophysiological mechanisms associated with the severity of refractory GERD in patients with SSc using objective motility tests and clinical markers, and to develop a diagnostic algorithm to guide personalized treatment based on the organ affected. Methods: This is a prospective clinical cohort study. Patients with SSc and symptoms of GERD refractory to PPIs will be included. Clinical, immunological, and demographic variables will be collected. Esophageal symptoms and quality-of-life impact will be assessed using validated questionnaires. Advanced gastrointestinal motility tests (gastric emptying scintigraphy and high-resolution intestinal manometry) will be performed to evaluate mechanisms associated with reflux severity (presence of erosive esophagitis and esophageal acid exposure). Relevance: This study addresses a common clinical challenge in patients with SSc: the persistence of GERD symptoms despite acid-suppressive treatment with PPIs. This project proposes to elucidate the pathophysiological mechanisms associated with GERD severity using motility tests available in clinical practice, and to develop a personalized approach based on objective motility assessment. This will allow the identification of the underlying mechanisms of treatment-refractory GERD and, in the future, the evaluation of targeted therapies addressing the associated dysmotility. The development of a diagnostic algorithm will support clinical decision-making, promote rational use of invasive tests, and optimize patient management, with a potential impact on improving quality of life and healthcare efficiency.

Conditions

• Systemic Sclerosis (SSc)
• GERD (Gastroesophageal Reflux Disease)

Interventions

Type	Name	Description
OTHER	educational healthcare intervention	This intervention will be applyed at the beginning of the study
DIAGNOSTIC_TEST	Objective assessment of GI motility	Objetive assessment of gastrointestinal dysmotility in GI organs (esophagus, stomach, small bowel) will be performed using state of the art tests.
DIAGNOSTIC_TEST	Evaluation of GERD severity	Objective evaluation of GERD severity on PPI therapy will be performed.

Timeline

• Start date: 2025-07-01
• Primary completion: 2027-07-01
• Completion: 2027-07-01
• First posted: 2025-06-15
• Last updated: 2025-06-15