Effect of a Combination of Hyaluronic Acid, Chondroitin Sulphate and Magnesium Trisilicate on Subjects With GastroEsophageal Reflux Disease

Study Overview
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Brief Summary
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The aim of this study is to investigate whether a 3-week treatment with an oral melt in mouth medical device, made up with hyaluronic acid, chondroitin sulphate and magnesium trisilicate, can lead to a reduction of Gastroesophageal Reflux Disease symptoms and to an improvement of the integrity of esophageal mucosa in patients who are to experiencing esophagus symptoms. The study is a randomized, double-blind cross-over placebo controlled study. Every patient will get both the active study device during one study period and placebo during another another period.

Official Title
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Effect of a Combination Oral Formulation of Hyaluronic Acid With Chondroitin Sulphate and With Magnesium Trisilicate on Mucosal Integrity and Reflux Exposure in Subjects With Gastro-Esophageal Reflux Disease Not Currently Treated With a Proton Pump Inhibitor: a Double-Blind, Placebo-Controlled, Randomized, Crossover Study

Conditions
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Gastro Esophageal Reflux

Intervention / Treatment
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* Device: hyaluronic acid with chondroitin + sulphate + magnesium trisilicate
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, age 18 to 75 years GERD as defined by an acid exposure time >4% on pH/impedance monitoring and/or esophagitis LA grade A or B on endoscopy Heartburn at least twice per week over the last 1 month ReQuest Symptoms sum score >3,37 at screening GERD patients not treated with a PPI in the previous 2 months Subjects capable of understanding and be willing to provide signed and dated written voluntary informed consent Exclusion Criteria: Patients suffering from gastrointestinal diseases other than GERD Esophagitis LA grade C or D or Barrett's esophagus on endoscopy Impaired kidney or liver function Significant cardiac, pulmonary or psychiatric comorbidity as judged by the investigator Medication use (including NSAIDS) that may interfere with GERD symptom assessment within 2 weeks before the start of the study or during the study Pregnancy or breast-feeding Females of childbearing potential in the absence of effective contraceptive methods History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements Treatment with any investigational drug within the previous 30 days Active malignancy of any type, or history of cancer, including solid tumors and hematological malignancies (except patients with malignancies that have been surgically removed and/or with no evidence of recurrence for at least five years before study enrolment) Inability to conform to protocol procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GERDOff® Plus<br>hyaluronic acid with chondroitin + sulphate + magnesium trisilicate Melt in mouth tablets (1100 mg). 1 tablet q.i.d. (three after meals, one before resting) for 3 consecutive weeks. After three weeks of wash-out period,patients will take either placebo or GERDOff® Plus q.i.d. (three after meals, one before resting) for another three weeks. | Device: hyaluronic acid with chondroitin + sulphate + magnesium trisilicate<br>* Melt in mouth tablets (1100 mg)<br>* Other names: GERDOff Plus;|
| Placebo Comparator: Placebo<br>Placebo melt in mouth tablets (1100 mg). 1 tablet q.i.d. (three after meals, one before resting) for three consecutive weeks. After three weeks of wash-out period,patients will take either placebo or GERDOff® Plus q.i.d. (three after meals, one before resting) for another three weeks. | Device: Placebo<br>* tablets with the same aspect of the active device<br>* Other names: Placebo (for hyaluronic acid with chondroitin + sulphate + magnesium trisilicate);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal Impedance | Change between groups in baseline impedance value. Impedance baseline values will be assessed in two steady periods of 30 seconds at the beginning and at the end of consecutive time windows of 30 minutes, 60 minutes. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal acid exposure | Esophageal acid exposure assessed by 24-hour pH-impedance measurement | 3 weeks | 
| Esophageal permeability | Esophageal permeability assessed by transepithelial electrical resistance | 3 weeks | 
| Microscopic esophagitis | Microscopic esophagitis evidence at endoscopy assessed by Esohisto score. The score assesses the severity of esophagitis through a score for each parameter ranging from 0 to 2 (0=normal, 2=severe). Parameters are: Basal cell layer hyperplasia; Papillary elongation; Dilated intercellular spaces; Intraepithelial eosinophils; Intraepithelial neutrophils; Intraepithelial mononuclear cells | 3 weeks | 
| Intercellular spaces | The presence (on endoscopy) and severity of dilated intercellular spaces assessed by transmission electron microscopy. | 3 weeks | 
| The expression of tight junctions | The expression of tight junction proteins at RNA, protein and immunohistochemistry level | 3 weeks | 
| ReQuest Questionnaire score | Change in ReQuest score for GERD symptoms severity evaluated through ReQuest Questionnaire. ReQuest is a self-assessed, dimension-orientated scale designed to evaluate the treatment response in patients suffering from erosive GERD. It assesses seven dimensions of GERD (acid complaints, upper abdominal/stomach complaints, lower abdominal/ digestive complaints, nausea, sleep disturbances, other complaints and general well-being). The intensity is measured on a 100-mm visual analogue scale and the frequency (except general well-being) on a 7-point Likert scale, ranging from 0 to more than 10 times per day. It asks for the occurrence of symptom descriptions known to be typical of the corresponding dimension | 3 weeks | 
| Esophageal reflux episodes | Total number of reflux episodes and their proximal extent, number of acid reflux events and their duration. | 3 weeks |