To assess the effect of Ziverel on esophageal sensitivity to acid, mucosal barrier function and reflux symptoms in patients with PPI-refractory reflux symptoms.
ID
Source
Brief title
Condition
- Gastrointestinal motility and defaecation conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the perfusion sensitivity score (acid perfusion
test).
Secondary outcome
Secondary endpoints are (1) symptom score improvement based on the RDQ
Questionnaire score, and (2) esophageal barrier function measured with Ussing
chamber experiments and electrical tissue impedance spectroscopy during
endoscopy.
Background summary
Approximately one third of the patients with gastroesophageal reflux disease
(GERD) has refractory symptoms despite daily proton pump inhibitor (PPI) use.
Several studies have suggested that an impaired mucosal barrier function might
underlie symptom perception and esophageal acid sensitivity, and thus
contributes to PPI-resistant symptoms. Therefore, impaired mucosal barrier
function is considered a potential therapeutic target in reflux disease.
Ziverel is a medical device that consists of hyaluronic acid and chondroitin
sulphate. It is a bio-adhesive formulation with tissue regenerating abilities
that coats the esophageal wall and thereby acts as a mechanical barrier against
the noxious components of refluxate. One ex vivo study model in pigs
demonstrated that Ziverel prevents acid perfusion-induced mucosal barrier
damage in the esophagus, but these effects still have to be confirmed in
humans. It has been demonstrated in prior studies that Ziverel combined with
PPIs indeed provided superior control of reflux symptoms in GERD patients
compared to placebo. However to date, this only has been investigated in a
limited number of studies and the underlying working mechanism in humans has
not been elucidated yet. Hence, more information on efficacy and mechanisms of
action is warranted.
Study objective
To assess the effect of Ziverel on esophageal sensitivity to acid, mucosal
barrier function and reflux symptoms in patients with PPI-refractory reflux
symptoms.
Study design
A prospective CE-marked medical device study with a double blind
placebo-controlled, randomized cross-over design.
Intervention
Patients will receive the first period either a placebo or Ziverel four times
daily for 14 days, followed by a second period in which they will receive the
other study medication. There will be a washout period (at least 14 days) in
between the two treatment periods. At the end of the two 14-day treatment
periods questionnaires are filled in, patients will undergo an upper endoscopy
with electrical tissue impedance spectroscopy and biopsy sampling for ex vivo
Ussing chamber experiments and an esophageal acid sensitivity test (modified
Bernstein test) will be performed. Patients will continue 2 times daily
standard dose of PPI for the entire duration of the study.
Study burden and risks
The subjects will have a total of three visits and will have to fill out
questionnaires on three separate occasions. Patients undergo two upper
endoscopies with biopsy sampling and two esophageal acid perfusion tests. Both
endoscopy and acid perfusion test cause mild discomfort. Sedation can be
provided on demand. Risk of perforation or bleeding of biopsy taking is smaller
than 1/10000 endoscopies. Participants will be compensated financially for
participation in the study and the findings could help treat future patients
with similar complaints.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Age above 18 years
- Symptoms of heartburn and/or acid regurgitation under PPI treatment for at least 3 months.
- Use of proton pump inhibitors at a standard two times daily dose for at least 4 weeks prior to inclusion, same dosage should be maintained during the entire study period.
Exclusion criteria
- Previous gastric or major gastrointestinal surgery other than appendectomy or cholecystectomy.
- Use of any other medication than proton pump inhibitors with a potential effect on gastrointestinal motility, secretion or sensitivity that cannot be stopped for the duration of the study (e.g. H2-blockers, antidepressants, prokinetics, antacids)
- Known Barrett*s esophagus
- History of gastrointestinal cancer
- Known allergy to one of the ingredients of Ziverel
- Severe and clinically unstable concomitant disease (e.g. liver, cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders)
- Pregnant, lactating or fertile women (without contraception)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66698.018.18 |