Systemic Sclerosis With DysphagiaPhase 2NCT06915181
Clinical Usefulness and Influence on Esophageal Motility of Pyridostigmine for Dysphagia in Systemic Sclerosis
A Phase 2 study testing Pyridostigmine in people with Systemic Sclerosis With Dysphagia, run by Universitair Ziekenhuis Brussel.
Trial summary
Systemic sclerosis is characterized by progressive fibrosis of different organ systems. With a longer duration, the risk of gastrointestinal involvement increases. There is a high prevalence of gastro-esophageal reflux disease (GERD) secondary to a severe insufficiency of the lower esophageal sphincter (LES)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis With Dysphagia
- What is being tested?
- Pyridostigmine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2023to 1 May 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 years or older;
- Known systemic sclerosis;
- Dysphagia with BEDQ score of 10 or more despite twice daily high dose PPI (omeprazole 40 mg b.i.d., esomeprazole 20 mg b.i.d., pantoprazole 40 mg b.i.d., lansoprazole 30 mg b.i.d.).
Who cannot join
- Presence of reflux oesophagitis grade C or more, eosinophilic oesophagitis, oesophageal stenosis (whether peptic or malignant);
- Prior oesophageal surgery, endoscopic resections, Radiofrequency Abla-tion for Barrett's mucosa or POEM;
- Prior gastric surgery;
- Prior diagnosis of major oesophageal motor disorder such as oesophageal spasm, achalasia, EGJ outflow obstruction;
- Prevention of major side effects by exclusion of certain patient groups
- Diarrhoea (defined as Bristol Stool Scale > 5) for more than 2 days per week in the past 2 weeks;
Show all 17Show fewer
- Uncontrolled asthma, exacerbation of COPD in the last 4 weeks;
- Known ischaemic heart condition or myocardial infarction in the last 4 weeks;
- Resting heart rate < 60 bpm;
- AV-block 2 or 3 (except after implantation of a pacemaker), or bradycardia < 60 bpm;
- Systolic blood pressure > 100 mmHg;
- Impaired renal function with glomerular filtration rate < 30 ml/min;
- Prior or current urinary obstruction;
- Previous treatment with pyridostigmine in the past 4 weeks;
- Treatment with anticholinergic agents in the past 4 weeks;
- Treatment with prokinetic agents during the past 4 weeks
- Pregnancy. Women of childbearing age will undergo a pregnancy test be-fore starting treatment and will be required to use at least 2 highly effective anticonception methods.
About this study
Systemic sclerosis is characterized by progressive fibrosis of different organ systems. With a longer duration, the risk of gastrointestinal involvement increases. There is a high prevalence of gastro-esophageal reflux disease (GERD) secondary to a severe insufficiency of the lower esophageal sphincter (LES), resulting in severe reflux esophagitis when left untreated. On the long run, this is associated with an elevated risk of esophageal bleeding, peptic stenosis, Barrett esophagus and associated risk of esophageal cancer. Apart from the insufficiency of the LES, esophageal aperistalsis is frequently observed. This results in prolonged esophageal contact with the refluxate due to insufficient clearance by the absence of adequate peristalsis. As a consequence of impaired peristalsis, patients with esophageal involvement in systemic sclerosis often experience dysphagia for solids, causing weight loss and malnu-trition, and reducing in quality of life.
To control reflux disease, high dose proton pump inhibitor therapy is part of the advocated treatment for esophageal involvement in systemic sclerosis. This therapy is highly effective in reducing acidic reflux, but has no influence on the esophageal motility disorder, leaving the dysphagia untreated. Because of the lack of a specific treatment targeting dysphagia, most patients eventually are advised to take conservative measures such as eating while sitting up straight, chewing well and flushing every food bolus with fluids.
Read more
While current treatment targets the acidic reflux, there is no accepted treatment to improve esophageal motility. In the presence of dysphagia patients are advocated to follow conservative measures like sitting upright when eating and drinking water to help passage of the bolus.
A cholinesterase inhibitor, pyridostigmine prevents the degradation of acetyl choline at the neuromuscular junction, prolonging its excitatory action. A recent uncontrolled study in patients suffering from systemic sclerosis identified a beneficial effect on gastro-intestinal symptoms, especially constipation. In healthy volunteers intake of pyridostigmine enhanced esophageal contractility as revealed by an increased amplitude of distal esophageal con-tractions. Despite this beneficial influence on esophageal motility there are no data on the possible therapeutic effects in patients with systemic sclerosis and esophageal involvement.
This study aims at evaluating the effects of pyridostigmine on symptoms of dysphagia. Additionally improvement of GERD symptoms and quality of life will be recorded. Improvement of parameters of esophageal motility as well as baseline esophageal impedance during esophageal contraction will also be assessed.
- Conditions
- Systemic Sclerosis With Dysphagia
- Being tested
- Pyridostigmine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridostigmineDrug
Subjects will participate in a double-blind randomized controlled cross-over trial. All patients will receive the study drug and placebo. Subjects and investigators will remain blinded to whether the subject receives active treatment during the first or second treatment period.
Participation in the study will last 10 weeks, with 4 weeks on active treatment and 4 weeks on placebo, with a 2-week wash-out period in between.
| Study group | Role | What they receive |
|---|---|---|
| Placebo first-then Pyridostigmine | Placebo comparator | Not described Receives: Drug: Pyridostigmine |
| Pyridostigmine first-then Placebo | Active comparator | Not described Receives: Drug: Pyridostigmine |
What is being measured
The primary outcome is the main question the study is designed to answer.
difference in FSSG score
decrease in FSSG score between treatment arms
Measured: from baseline till visit 4 (week 10)
Secondary outcomes (8)
difference in BEDQ score
decrease in BEDQ score between treatment arms
Measured: from baseline till visit 4 (week 10)
change in quality of life between treatment arms
change in quality of life assessed by SF-36 between treatment arms
Measured: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
differences between mean distal contractility integral
Measured: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
differences between mean distal latency
Measured: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
differences between resting pressure of the lower oesophageal sphincter
Measured: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
differences between percentage of succesful bolus clearance
Measured: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
differences between percentage of normal peristalsis
Measured: from baseline till visit 4 (week 10)
changes in oesophageal baseline impedance between treatment arms
differences between oesophageal contraction
Measured: from baseline till visit 4 (week 10)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start1 Dec 2023
- Primary completion1 May 2024
- Study completion1 May 2024
Why it stopped: Logistically the study had to be stopped.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Sclerosis With DysphagiaStudies of the same condition, open and under way.
- More trials run by Universitair Ziekenhuis BrusselThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06915181
- Sponsor's protocol ID
- PySyS
- Status last verified
- Mar 2025
- First submitted
- 18 Apr 2023
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Usefulness and Influence on Esophageal Motility of Pyridostigmine for Dysphagia in Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT06915181
- Acronym / sponsor ID
- PySyS
- Conditions
- Systemic Sclerosis With Dysphagia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Logistically the study had to be stopped.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- 1 Dec 2023 (actual)
- Primary completion
- 1 May 2024 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 8 Apr 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.
Systemic sclerosis is characterized by progressive fibrosis of different organ systems. With a longer duration, the risk of gastrointestinal involvement increases. There is a high prevalence of gastro-esophageal reflux disease (GERD) secondary to a severe insufficiency of the lower esophageal sphincter (LES), resulting in severe reflux esophagitis when left untreated. On the long run, this is associated with an elevated risk of esophageal bleeding, peptic stenosis, Barrett esophagus and associated risk of esophageal cancer. Apart from the insufficiency of the LES, esophageal aperistalsis is frequently observed. This results in prolonged esophageal contact with the refluxate due to insufficient clearance by the absence of adequate peristalsis. As a consequence of impaired peristalsis, patients with esophageal involvement in systemic sclerosis often experience dysphagia for solids, causing weight loss and malnu-trition, and reducing in quality of life.
To control reflux disease, high dose proton pump inhibitor therapy is part of the advocated treatment for esophageal involvement in systemic sclerosis. This therapy is highly effective in reducing acidic reflux, but has no influence on the esophageal motility disorder, leaving the dysphagia untreated. Because of the lack of a specific treatment targeting dysphagia, most patients eventually are advised to take conservative measures such as eating while sitting up straight, chewing well and flushing every food bolus with fluids.
While current treatment targets the acidic reflux, there is no accepted treatment to improve esophageal motility. In the presence of dysphagia patients are advocated to follow conservative measures like sitting upright when eating and drinking water to help passage of the bolus.
A cholinesterase inhibitor, pyridostigmine prevents the degradation of acetyl choline at the neuromuscular junction, prolonging its excitatory action. A recent uncontrolled study in patients suffering from systemic sclerosis identified a beneficial effect on gastro-intestinal symptoms, especially constipation. In healthy volunteers intake of pyridostigmine enhanced esophageal contractility as revealed by an increased amplitude of distal esophageal con-tractions. Despite this beneficial influence on esophageal motility there are no data on the possible therapeutic effects in patients with systemic sclerosis and esophageal involvement.
This study aims at evaluating the effects of pyridostigmine on symptoms of dysphagia. Additionally improvement of GERD symptoms and quality of life will be recorded. Improvement of parameters of esophageal motility as well as baseline esophageal impedance during esophageal contraction will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo first-then Pyridostigmine | Placebo comparator | Drug: Pyridostigmine |
| Pyridostigmine first-then Placebo | Active comparator | Drug: Pyridostigmine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients aged 18 years or older;
- Known systemic sclerosis;
- Dysphagia with BEDQ score of 10 or more despite twice daily high dose PPI (omeprazole 40 mg b.i.d., esomeprazole 20 mg b.i.d., pantoprazole 40 mg b.i.d., lansoprazole 30 mg b.i.d.).
Key exclusion criteria (17 listed)
- Presence of reflux oesophagitis grade C or more, eosinophilic oesophagitis, oesophageal stenosis (whether peptic or malignant);
- Prior oesophageal surgery, endoscopic resections, Radiofrequency Abla-tion for Barrett's mucosa or POEM;
- Prior gastric surgery;
- Prior diagnosis of major oesophageal motor disorder such as oesophageal spasm, achalasia, EGJ outflow obstruction;
- Prevention of major side effects by exclusion of certain patient groups
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 |
|---|---|---|
| PyridostigmineSubjects will participate in a double-blind randomized controlled cross-over trial. All patients will receive the study drug and placebo. Subjects and investigators will remain blinded to whether the subject receives active treatment during the first or second treatment period. Participation in the study will last 10 weeks, with 4 weeks on active treatment and 4 weeks on placebo, with a 2-week wash-out period in between. | Drug | Placebo first-then Pyridostigmine, Pyridostigmine first-then Placebo |
Primary outcome
difference in FSSG score
Time frame: from baseline till visit 4 (week 10)
decrease in FSSG score between treatment arms
8 secondary outcomes
difference in BEDQ score
Time frame: from baseline till visit 4 (week 10)
change in quality of life between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in high resolution manometry between treatment arms
Time frame: from baseline till visit 4 (week 10)
changes in oesophageal baseline impedance between treatment arms
Time frame: from baseline till visit 4 (week 10)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridostigmine in people with Systemic Sclerosis With Dysphagia, run by Universitair Ziekenhuis Brussel.
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 3 inclusion and 17 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: withdrawn, as of the sponsor's last update on 8 Apr 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
difference in FSSG score (time frame: from baseline till visit 4 (week 10)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2025.