Phase IV Study of the Impact of Dietary Fibers on Symptoms and Esophageal Motility in Patients With Non-erosive GERD

Study Overview
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Brief Summary
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Gastroesophageal reflux disease (GERD) is a chronic condition, which may significantly decrease patients' quality of life due to the typical symptoms - heartburn and regurgitation. These are caused by increasing number of transient lower esophageal sphincter relaxations, regularly recurring reflux of gastric content into oesophagus, acidification of the esophagus and consequent esophageal mucosa damage. In addition, an important role is played by the increase in production of hydrochloric acid in the stomach, the slowdown in the evacuation of the contents from the stomach and increase of gastric and intra-abdominal pressure. All of these factors may depend on the patient's diet. Theoretical premises of the positive influence of including dietary fiber on the course of gastroesophageal reflux disease may be the fact that dietary fiber may absorb nitric oxide (NO) containing in food, which in turn has relaxing effects on the lower esophageal sphincter. In addition, fiber deficiency has been shown to be associated with increased chance of developing hiatal hernia, which is associated with greater risk of the disease manifestations. There is lack of data to confirm that dietary interventions like higher dietary fiber intake may lead to lower frequency of GERD symptoms and influence objective criteria (those, obtained during esophageal pH-impedance (here and further: pH - pondus hydrogenii, i.e. quantity of hydrogen, a scale to measure acidity of a solution) recording and high resolution esophageal manometry). Mucofalk® is a drug of plant origin, consisting of a shell seeds of Plantago ovata (ispaghula, psyllium). High content of mucuses in the composition of psyllium seed allows it to include to group of soft food fibers, which has fundamental value for the appointment of a drug at a number of diseases, when, for example, the use of coarse food fibres not recommended or contraindicated. Mucofalk is the registered medicinal (registration number of the Russian State register of medicines P N014176/01, registration date 14.07.2008, manufacturer: Lozan Pharma Gesellschaft mit beschränkter Haftung (GmbH), packager: Dr. Falk Pharma GmbH, Germany). Recommended dosage and administration: orally, adults and children over 12 years - 1 pack. 2-6 times a day. Before use, the contents of 1 packet poured in a glass, in which slowly poured with cold water (150 ml), stir and drink immediately. Then drink another glass of liquid.

Detailed Description
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During the study 14-days screening period is provided to evaluate H.pylori and endoscopic status of the patient and to confirm the presence of dietary fiber deficiency (based on standard computerized dietary questionnaire). On the baseline physical examination, GERD-Q questionnaire, GERD symptom severity scale (by Likert), Bristol stool scale, high resolution esophageal manometry and 24-hours esophageal pH-impedance studies are to be provided. Since baseline, up to day 10 Mucofalk 15 g/day in three times a day (TID) regimen is to be given. All the patient will receive standardized menu. Repeat evaluation of symptoms, high resolution esophageal manometry and 24-hours esophageal pH-impedance are to be done at the day 10 of the study.

Official Title
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Phase IV Non Comparative Study of the Impact of Dietary Fiber Deficiency Correction Using Mucofalk® on Clinical Features and Motor Function of the Esophagus in Patients With Non-erosive Gastroesophageal Reflux Disease

Conditions
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Gastroesophageal Reflux Disease

Intervention / Treatment
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* Drug: Mucofalk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of non-erosive form of Gastroesophageal Reflux disease Dietary fiber deficiency by dietary questionnaire pathological gastroesophageal reflux by 24-hours esophageal pH-impedance examination willingness to participate (signed informed consent) Exclusion Criteria: presence of esophageal mucosal damages (esophagitis) by endoscopic evaluation gastrointestinal surgery in anamnesis current pregnancy or breast-feeding known hypersensitivity to Mucofalk or its components

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mucofalk<br>Mucofalk 15 g/day i.e. 5 g TID per os, 15-20 min before meal | Drug: Mucofalk<br>* Mucofalk 15 g/day i.e. 5 g TID per os, 15-20 min before meal<br>* Other names: Psyllium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gastroesophageal Refluxes | Number of gastroesophageal refluxes registered with 24-hours esophageal pH-impedance on the 10th day of psyllium intake. Statistical data represent the results of the comparison of the data obtained on the day 10 of study (EOT) with the baseline characteristics provided in the specific section | End of Treatment, on day 10 of psyllium intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acid Exposure Time | Percent of time with pH less than 4 at 5 cm above upper border of lower oesophageal sphincter per 24-hours oesophageal pH-impedance recording on the day 10 of psyllium intake. This outcome measure was compared to the baseline characteristics provided in the specific section of the study description | End of Treatment, on day 10 of psyllium intake | 
| Number of Acid Gastroesophageal Refluxes | Number of acid refluxes was measured by 24-hours oesophageal pH-impedance recordings. Reflux was considered as acid when oesophageal pH was less than 4 and the impedance revealed backward flow of the stomach content into the oesophagus. Outcome measure reflects the data of day 10 of psyllium intake. Statistics reflects comparison between EOT and baseline data. | End of Treatment, on day 10 of psyllium intake | 
| Number of Patients Experiencing Heartburn During 7 Days Prior the Day 10 of Psyllium Intake | Presence of heartburn during 7 days prior to the day 10 of psyllium intake was evaluated with a standardized questionnaire. This result was assessed at EOT | 7 days prior to EOT | 
| Minimal Lower Esophageal Sphincter Pressure at Rest | Obtained during esophageal high resolution manometry study. End of treatment data were compared to the baseline. Per standard, resting pressure is measured during 30 seconds. High resolution manometry data on day 10 was compared to baseline. | End of Treatment, on day 10 of psyllium intake | 
| Mean Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows at the End of Treatment (the Day 10 of Psyllium Intake) | The data are obtained during high resolution esophageal manometry study on the day 10 of psyllium intake. This outcome is measured after 10 water swallows by 5 ml each. The study usually lasts for about 15 to 20 minutes. Data of high-resolution esophageal manometry examination at baseline and on the day 10 of psyllium intake were compared. | End of Treatment, on day 10 of psyllium intake | 
| Minimal Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows | The results obtained during high resolution esophageal manometry studies. This parameter is obtained after 10 water swallows by 5 ml each. Data of high resolution esophageal manometry (examination usually lasts for 10-20 min) on the day 10 of psyllium intake were compared to the baseline characteristics. The data were compared to baseline characteristics | End of Treatment, on day 10 of psyllium intake | 
| Residual Lower Esophageal Sphincter Pressure | These data are obtained during high resolution esophageal manometry studies. The end of treatment characteristics were compared to the baseline ones. | End of Treatment, on day 10 of psyllium intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GERD, psyllium, Lower esophageal sphincter, Esophageal motility, Dietary fiber, Heartburn, gastroesophageal reflux, non-erosive gastroesophageal reflux disease