Gastroesophageal Reflux Disease
Conditions
Keywords
GERD, psyllium, Lower esophageal sphincter, Esophageal motility, Dietary fiber, Heartburn, gastroesophageal reflux, non-erosive gastroesophageal reflux disease
Brief summary
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
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.
Interventions
DRUGMucofalk
Mucofalk 15 g/day i.e. 5 g TID per os, 15-20 min before meal
Sponsors
Dr. Falk Pharma GmbH
Russian Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Gastroesophageal Refluxes | End of Treatment, on day 10 of psyllium intake | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acid Exposure Time | End of Treatment, on day 10 of psyllium intake | 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 |
| Number of Acid Gastroesophageal Refluxes | End of Treatment, on day 10 of psyllium intake | 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. |
| Number of Patients Experiencing Heartburn During 7 Days Prior the Day 10 of Psyllium Intake | 7 days prior to EOT | 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 |
| Minimal Lower Esophageal Sphincter Pressure at Rest | End of Treatment, on day 10 of psyllium intake | 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. |
| Minimal Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows | End of Treatment, on day 10 of psyllium intake | 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 |
| Residual Lower Esophageal Sphincter Pressure | End of Treatment, on day 10 of psyllium intake | These data are obtained during high resolution esophageal manometry studies. The end of treatment characteristics were compared to the baseline ones. |
| Mean Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows at the End of Treatment (the Day 10 of Psyllium Intake) | End of Treatment, on 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Lower Esophageal Sphincter Pressure (at Rest) | End of Treatment, on day 10 of psyllium intake | This parameter is obtained with the use of high-resolution esophageal manometry performed on the Day 10 of psyllium intake. |
| Stools Per Week | 7 days | Episodes of stools were calculated during 7-day period. Mean number at the end point was compared to the baseline one |
Countries
Russia
Participant flow
Recruitment details
36 patients were enrolled. 1 patient withdrew informed consent before day 0, 1 excluded due to non-compliance, 1 could not tolerate oesophageal manometry, in 1 case there was no possibility to perform the manometry. Migration of the pH-impedance probe was found in two patients. The data of these mentioned 6 patients were excluded from the analysis
Participants by arm
| Arm | Count |
|---|---|
| Mucofalk Mucofalk 15 g/day i.e. 5 g TID per os, 15-20 min before meal
Mucofalk: Mucofalk 15 g/day i.e. 5 g TID per os, 15-20 min before meal | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | inadequate pH-impedance tracings | 2 |
| Overall Study | Intolerance of esophageal manometry | 1 |
| Overall Study | no possibility to place the catheter | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Mucofalk |
|---|---|
| Acid exposure time | 5.6 Percent of time pH<4 per 24-hours period STANDARD_DEVIATION 4.8 |
| Age, Continuous | 34.7 years STANDARD_DEVIATION 9.3 |
| alcohol intake (yes) | 14 Participants |
| alcohol use (g/day) | 1.1 g/day STANDARD_DEVIATION 1.7 |
| basal dietary fiber intake, g/day | 6.0 g/day STANDARD_DEVIATION 2.3 |
| body mass index, kg/m^2 | 36.7 kg/m^2 STANDARD_DEVIATION 6.9 |
| hiatal hernia presence | 16 Participants |
| hiatal hernia size | 0.9 cm STANDARD_DEVIATION 0.5 |
| Mean Lower Esophageal Sphincter Pressure (at Rest) | 22.0 mm Hg STANDARD_DEVIATION 9.4 |
| Mean resting lower esophageal sphincter (LES) pressure after 10 water swallows | 20.5 mm Hg STANDARD_DEVIATION 9.5 |
| minimal lower esophageal sphincter pressure at rest, mm Hg | 22.0 mm Hg STANDARD_DEVIATION 9.4 |
| Minimal Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows | 14.1 mm Hg STANDARD_DEVIATION 8 |
| Number of acid gastroesophageal refluxes | 43.2 acid refluxes per day STANDARD_DEVIATION 14.7 |
| Number of Gastroesophageal Refluxes | 67.9 refluxes a day STANDARD_DEVIATION 17.7 |
| Number of patients experiencing heartburn during 7 days prior to baseline | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment Russia | 30 participants |
| Residual Lower Esophageal Sphincter Pressure | 7.5 mm Hg STANDARD_DEVIATION 6.1 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 18 Participants |
| smoking status (yes) | 6 Participants |
| stools per week, n | 7.0 stools per week STANDARD_DEVIATION 2 |
| weight, kg | 82.5 kg STANDARD_DEVIATION 17.9 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 35 |
| other Total, other adverse events | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 |
Outcome results
Primary
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
Time frame: End of Treatment, on day 10 of psyllium intake
Population: Thirty-six patients were enrolled, complete data from 30 were included in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Number of Gastroesophageal Refluxes | 42.4 refluxes | Standard Deviation 13.5 |
Comparison: Data were analyzed using Statistica 10 software. Wilcoxon matched pairs test of non-parametric module was used to assess changes of the studied parameters after the course of fiber supplementation in comparison to baseline. A P value of 0.05 was considered statistically significant. Sample size calculation was performed using 1-Way ANOVA. Effect size calculation was performed for every comparison.p-value: 0.000002Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: End of Treatment, on day 10 of psyllium intake
Population: Thirty-six patients were enrolled, complete data from 30 were included in the final analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Acid Exposure Time | 5.5 Percent of time pH<4 per 24-hours period | Standard Deviation 7.57 |
Comparison: Data were analyzed using Statistica 10 software. Wilcoxon matched pairs test of non-parametric module was used to assess changes of the studied parameters after the course of fiber supplementation in comparison to baseline. A P value of 0.05 was considered statistically significant. Sample size calculation was performed using 1-Way ANOVA. Effect size calculation was performed for every comparison.p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 patients enrolled, data of the 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Mean Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows at the End of Treatment (the Day 10 of Psyllium Intake) | 22.0 mm Hg | Standard Deviation 10.3 |
p-value: 0.11Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 patients were enrolled. data of the 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Minimal Lower Esophageal Sphincter Pressure at Rest | 11.3 mm Hg | Standard Deviation 9.4 |
p-value: 0.023Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 patients were enrolled, data of 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Minimal Resting Lower Esophageal Sphincter (LES) Pressure After 10 Water Swallows | 14.9 mm Hg | Standard Deviation 6.4 |
p-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 subjects were enrolled, data of 30 of them were included to the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Number of Acid Gastroesophageal Refluxes | 30.3 acid refluxes | Standard Deviation 15.3 |
p-value: 0.002415Wilcoxon (Mann-Whitney)
Secondary
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
Time frame: 7 days prior to EOT
Population: 36 patients were enrolled, data of 30 of them were included to the final analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mucofalk | Number of Patients Experiencing Heartburn During 7 Days Prior the Day 10 of Psyllium Intake | 12 Number of participants |
p-value: 0.000438Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 non-erosive reflux disease (NERD) patients were enrolled, the data of 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Residual Lower Esophageal Sphincter Pressure | 7.0 mm Hg | Standard Deviation 5.4 |
p-value: 0.94Wilcoxon (Mann-Whitney)
Other Pre-specified
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.
Time frame: End of Treatment, on day 10 of psyllium intake
Population: 36 subjects were enrolled, data of 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Mean Lower Esophageal Sphincter Pressure (at Rest) | 26.5 mm Hg | Standard Deviation 11.3 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Other Pre-specified
Stools Per Week
Episodes of stools were calculated during 7-day period. Mean number at the end point was compared to the baseline one
Time frame: 7 days
Population: 36 patients were enrolled, complete data of 30 of them were available for the final analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mucofalk | Stools Per Week | 8.0 stools per week | Standard Deviation 3 |
p-value: 0.00002Wilcoxon (Mann-Whitney)