Systemic Sclerosis (SSc)NCT07022912
PPI Refractory - GERD Mechanisms in Systemic Sclerosis
An observational study of Systemic Sclerosis (SSc) and GERD (Gastroesophageal Reflux Disease), run by Hospital Universitari Vall d'Hebron Research Institute.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Systemic Sclerosis (SSc), GERD (Gastroesophageal Reflux Disease)
- What is being tested?
- educational healthcare intervention, Objective assessment of GI motility and Evaluation of GERD severity
- How many people
- 147 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2025to 1 Jul 2027
- How long will I take part?
- 5 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Objective Assessment of Gastrointestinal Involvement in Patients With Systemic Sclerosis and Gastroesophageal Reflux Symptoms Refractory to Proton Pump Inhibitors.
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.
Read the 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.
- Being tested
- educational healthcare intervention, Objective assessment of GI motility, Evaluation of GERD severity
- Keywords
- GERD mechanisms, gastrointestinal involvement, systemic sclerosis
- Medical subject headings
- Scleroderma, Systemic, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
educational healthcare interventionOther
Also called avoiding late dinners, not lying down for at least 2 hours after meals, avoiding tobacco and alcohol, avoiding large or high-fat meals
This intervention will be applyed at the beginning of the study
Objective assessment of GI motilityDiagnostic test
Also called Gastric emptying test, Small bowel manometry, High-resolution esophageal manometry, Abdominal CT scan
Objetive assessment of gastrointestinal dysmotility in GI organs (esophagus, stomach, small bowel) will be performed using state of the art tests.
Evaluation of GERD severityDiagnostic test
Also called upper GI endoscopy (on PPI), pH-impedance monitoring (on PPI)
Objective evaluation of GERD severity on PPI therapy will be performed.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: educational healthcare intervention; Diagnostic Test: Objective assessment of GI motility; Diagnostic Test: Evaluation of GERD severity |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the end of double PPI and health intervention period (8 - 12 weeks)
Secondary outcomes (1)
Gastrointestinal dysmotility associations
prevalence of delayed gastric emptying, esophageal dysmotility and small bowel dysmotility.
Measured: After 8 weeks on double PPI therapy, during week 8 to 12.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2025
- Study start1 Jul 2025 (estimated)
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic Sclerosis (SSc)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 147 participants (estimated)
- Target duration
- 5 Months
Sponsor and investigators
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07022912
- Sponsor's protocol ID
- PR(AG)185/2025
- Status last verified
- Jun 2025
- First submitted
- 6 Jun 2025
- Last updated
- 15 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39609018Alcala-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.
PubMed 39250735
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Objective Assessment of Gastrointestinal Involvement in Patients With Systemic Sclerosis and Gastroesophageal Reflux Symptoms Refractory to Proton Pump Inhibitors.
- ClinicalTrials.gov ID
- NCT07022912
- Acronym / sponsor ID
- PR(AG)185/2025
- Keywords
- GERD mechanisms, gastrointestinal involvement, systemic sclerosis
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 147 participants (estimated)
- Lead sponsor
- Hospital Universitari Vall d'Hebron Research InstituteUniversity, hospital or other
- Study start
- 1 Jul 2025 (estimated)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 15 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients with SSc and PPI-refractory GERD symptoms | – | Other: educational healthcare intervention, Diagnostic Test: Objective assessment of GI motility, Diagnostic Test: Evaluation of GERD severityStudy 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| educational healthcare interventionAlso: avoiding late dinners, not lying down for at least 2 hours after meals, avoiding tobacco and alcohol, avoiding large or high-fat mealsThis intervention will be applyed at the beginning of the study | Other | patients with SSc and PPI-refractory GERD symptoms |
| Objective assessment of GI motilityAlso: Gastric emptying test, Small bowel manometry, High-resolution esophageal manometry, Abdominal CT scanObjetive assessment of gastrointestinal dysmotility in GI organs (esophagus, stomach, small bowel) will be performed using state of the art tests. | Diagnostic test | patients with SSc and PPI-refractory GERD symptoms |
| Evaluation of GERD severityAlso: upper GI endoscopy (on PPI), pH-impedance monitoring (on PPI)Objective evaluation of GERD severity on PPI therapy will be performed. | Diagnostic test | patients with SSc and PPI-refractory GERD symptoms |
Primary outcome
Prevalence of PPI-refractory GERD
Time frame: At the end of double PPI and health intervention period (8 - 12 weeks)
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.
1 secondary outcome
Gastrointestinal dysmotility associations
Time frame: After 8 weeks on double PPI therapy, during week 8 to 12.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2025.
- Background: PubMed 39609018Alcala-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.
- Background: PubMed 39250735Alcala-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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Sclerosis (SSc) and GERD (Gastroesophageal Reflux Disease), run by Hospital Universitari Vall d'Hebron Research Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Luis G Alcala-Gonzalez, MD PhD (934893000 ext. 2896, luisgerardo.alcala@vallhebron.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of PPI-refractory GERD (time frame: At the end of double PPI and health intervention period (8 - 12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07022912, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.