PPI Refractory - GERD Mechanisms in Systemic Sclerosis

NCT07022912 | Not Yet Recruiting

• 1 other identifier: PR(AG)185/2025
• Study Type: observational
• Target: 147
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

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

Keywords

GERD mechanisms; gastrointestinal involvement; systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Prevalence of PPI-refractory GERD

  The presence of erosive esophagitis B,C, or D on endoscopy, acid exposure time \> 4% or \> 80 reflux episodes, as per Lyon 2.0 criteria, will be considered refractory GERD.

  At the end of double PPI and health intervention period (8 - 12 weeks)

Secondary Outcomes (1)

• Gastrointestinal dysmotility associations

  After 8 weeks on double PPI therapy, during week 8 to 12.

Study Arms (1)

patients with SSc and PPI-refractory GERD symptoms

Study Subjects: Patients will be recruited from the outpatient clinics of the Autoimmune Diseases Unit or the Gastroenterology Department at the Vall d'Hebron University Hospital (HUVH), Barcelona. Inclusion Criteria: Diagnosis of systemic sclerosis according to the 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria and/or LeRoy criteria. Age ≥ 18 years. Presence of gastroesophageal reflux symptoms, defined as heartburn and/or regurgitation occurring at least three times per week over the past three months, despite ongoing treatment with PPIs.

Other: educational healthcare intervention; Diagnostic Test: Objective assessment of GI motility; Diagnostic Test: Evaluation of GERD severity

Interventions

educational healthcare intervention OTHER

This intervention will be applyed at the beginning of the study

Also known as: avoiding late dinners, not lying down for at least 2 hours after meals, avoiding tobacco and alcohol, avoiding large or high-fat meals

patients with SSc and PPI-refractory GERD symptoms

Objective assessment of GI motility DIAGNOSTIC_TEST

Objetive assessment of gastrointestinal dysmotility in GI organs (esophagus, stomach, small bowel) will be performed using state of the art tests.

Also known as: Gastric emptying test, Small bowel manometry, High-resolution esophageal manometry, Abdominal CT scan

patients with SSc and PPI-refractory GERD symptoms

Evaluation of GERD severity DIAGNOSTIC_TEST

Objective evaluation of GERD severity on PPI therapy will be performed.

Also known as: upper GI endoscopy (on PPI), pH-impedance monitoring (on PPI)

patients with SSc and PPI-refractory GERD symptoms

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with systemic sclerosis and PPI-refractory reflux symptoms who are members of the Spanish Association of Patients with Systemic Sclerosis and/or those recruited from outpatient clinics at participating centers.

You may qualify if:

• Systemic sclerosis by ACR/EULAR 2023 criteria AND/OR Leroy Medsger classification criteria
• Reflux symptoms (Heartburn AND/OR Regurgitation), at least 3 times a week over the last 3 months despite PPI therapy

You may not qualify if:

• Previous surgery altering the anatomy or motility of the upper digestive tract, including fundoplication, esophageal myotomy, gastrectomy, or bariatric surgery.
• Severe pulmonary or cardiac disease requiring intravenous vasodilators, continuous oxygen therapy, or ventricular assist devices, preventing the performance of gastrointestinal motility tests.
• Pregnancy at the time of evaluation or planned pregnancy during the duration of the study.
• Neuromuscular disorders other than systemic sclerosis that may affect gastrointestinal motility.
• Prior diagnosis of functional gastrointestinal disorders, such as irritable bowel syndrome or functional dyspepsia, that may interfere with the interpretation of results.

Sponsors & Collaborators

• Hospital Universitari Vall d'Hebron Research Institute: lead

Related Publications (2)

• Alcala-Gonzalez LG, Guillen-Del-Castillo A, Aguilar A, Barber C, Codina C, Marin Garcia A, Malagelada C, Simeon-Aznar CP. Impact of gastrointestinal symptoms and psychological distress on quality of life in systemic sclerosis: a cross-sectional study. BMJ Open. 2024 Nov 27;14(11):e089725. doi: 10.1136/bmjopen-2024-089725.

  PMID: 39609018 BACKGROUND

• Alcala-Gonzalez LG, Guillen-Del-Castillo A, Aguilar Cayuelas A, Barber Caselles C, Codina-Clavaguera C, Marin Garcia A, Serra J, Malagelada C, Simeon-Aznar CP. Gastrointestinal dysmotility is associated with proton pump inhibitor refractory oesophagitis in patients with systemic sclerosis. Rheumatology (Oxford). 2025 May 1;64(5):3074-3079. doi: 10.1093/rheumatology/keae481.

  PMID: 39250735 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Gastroesophageal Reflux

Interventions

Postprandial Period; Ethanol; Endoscopy, Digestive System

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena; Alcohols; Organic Chemicals; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Central Study Contacts

Luis G Alcala-Gonzalez, MD PhD

CONTACT

934893000; luisgerardo.alcala@vallhebron.cat

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 15, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: June 15, 2025

Record last verified: 2025-06