Phase IV Study of the Impact of Dietary Fibers on Symptoms and Esophageal Motility in Patients With Non-erosive GERD (OGIG-130-1)

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

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.

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Mucofalk

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115446
    • Research Institute of Nutrition of Russian Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Lower Esophageal Sphincter Pressure (at Rest)	This parameter is obtained with the use of high-resolution esophageal manometry performed on the Day 10 of psyllium intake.	End of Treatment, on day 10 of psyllium intake
Stools Per Week	Episodes of stools were calculated during 7-day period. Mean number at the end point was compared to the baseline one	7 days

Collaborators and Investigators

• Sponsor: Russian Academy of Medical Sciences
• Collaborators: Dr. Falk Pharma GmbH
• Investigators: Study Chair: Vasily A Isakov, MD,PhD,AGAF, Fed. Research Center of Nutrition and Biotechnology, Gastroenterology&Hepatology; Principal Investigator: Sergey Morozov, MD, PhD, Fed. Research Center of Nutrition and Biotechnology, Gastroenterology&Hepatology

Publications and helpful links

General Publications

• Ronkainen J, Aro P, Storskrubb T, Lind T, Bolling-Sternevald E, Junghard O, Talley NJ, Agreus L. Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study. Aliment Pharmacol Ther. 2006 Jun 15;23(12):1725-33. doi: 10.1111/j.1365-2036.2006.02952.x.
• Terry P, Lagergren J, Ye W, Wolk A, Nyren O. Inverse association between intake of cereal fiber and risk of gastric cardia cancer. Gastroenterology. 2001 Feb;120(2):387-91. doi: 10.1053/gast.2001.21171.
• Burkitt DP, James PA. Low-residue diets and hiatus hernia. Lancet. 1973 Jul 21;2(7821):128-30. doi: 10.1016/s0140-6736(73)93067-5. No abstract available.
• Nilsson M, Johnsen R, Ye W, Hveem K, Lagergren J. Lifestyle related risk factors in the aetiology of gastro-oesophageal reflux. Gut. 2004 Dec;53(12):1730-5. doi: 10.1136/gut.2004.043265.
• El-Serag HB, Satia JA, Rabeneck L. Dietary intake and the risk of gastro-oesophageal reflux disease: a cross sectional study in volunteers. Gut. 2005 Jan;54(1):11-7. doi: 10.1136/gut.2004.040337.
• Karamanolis G, Tack J. Nutrition and motility disorders. Best Pract Res Clin Gastroenterol. 2006;20(3):485-505. doi: 10.1016/j.bpg.2006.01.005.

Helpful Links

• Official web-site of Institute of Nutrition (ION)
• Dr. Falk Pharma Gmbh
• published data

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 16, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 20, 2013

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: July 31, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: GERD; Heartburn; Dietary fiber; gastroesophageal reflux; Esophageal motility; psyllium; Lower esophageal sphincter; non-erosive gastroesophageal reflux disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Gastrointestinal Agents; Cathartics; Psyllium
• Other Study ID Numbers: ION RAMS; RussianAMS-1 (Other Identifier: RussianAMS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol, results of the study could be shared
• IPD Sharing Time Frame: within 2 years after study completion
• IPD Sharing Access Criteria: Official regulatory institutions request, official request by researchers or researchers organizations
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)