Healthy Volunteers
Conditions
Keywords
human Gut Microbiota, gut microbiota, gut microbiome, probiotic, antibiotic, antibiotic-associated diarrhea, intestinal bacterial overgrowth
Brief summary
The purpose of this study is to compare and contrast the effects of the probiotic Saccharomyces boulardii, the antibiotic amoxicillin/clavulanate and the combination on the gut microbiota of healthy volunteers.
Interventions
DIETARY_SUPPLEMENTSaccharomyces boulardii
500 mg, 2 times daily for 14 days
875/125 mg 2 times daily at least 1 hour before meals for 7 days
Sponsors
Biocodex
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 65 years (male or female) * Good general health * Able to comply with study requirements and to provide informed consent * For women of childbearing potential oA negative urine pregnancy test immediately prior to starting the study treatment oAgreement to comply with approved methods of contraception during the period of active study treatment (not required during follow-up)
Exclusion criteria
* History of organ transplantation * Known chronic or recurrent systemic disorder associated with immunocompromise * A history of allergy or hypersensitivity to Saccharomyces boulardii, brewer's or baker's yeast, amoxicillin, penicillins, or cephalosporins * History of severe allergic reaction (requiring hospital admission and/or the administration of parenteral medication or associated with dyspnoea, wheezing, hypotension, loss of consciousness). * Oral or systemic antibacterial therapy during the 3 months prior to study enrollment * New prescription medications during the 4 weeks prior to study enrollment * Prescription, OTC medications or supplements that are known to alter gut function or microflora (i.e. acid antisecretory drugs, probiotics) during the 4 weeks prior to study enrollment * Active gastrointestinal disease * Patients with a central venous catheter * Patients taking antifungals or laxatives within 14 days of enrolment * Patients enrolled in other clinical trials within the past 60 days * Prior gastrointestinal surgery (apart from appendectomy or cholecystectomy) * History of chronic constipation with passage of fewer than 3 bowel movements per week on average * Any condition or personal circumstance that, in the opinion of the investigator, renders the subject unlikely or unable to comply with the full study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal Symptom Rating Scale | Day 0 | Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms |
| Gastrointestinal Symptoms Response Score | Day 14 | Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms |
| Gastrointestinal Symptoms Response Scale | Day 21 | Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms |
| Prevalence of Escherichia in Stool | Day -7 to Day 21 | Control arm was not assessed as there was no intervention for this group. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21 |
| Operational Taxonomic Units | Day 0 to Day 21 | Core Microbiome includes control samples and baseline samples (Day -7 and Day 0) for antibiotic, probiotic, and combination groups. Data for Core microbiome for individual arms are not available. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prebiotic (Saccharomyces Boulardii) Saccharomyces boulardii: 500 mg, 2 times daily for 14 days | 13 |
| Antibiotic (Amoxicillin Clavulanate) Amoxicillin Clavulanate: 875/125 mg 2 times daily at least 1 hour before meals for 7 days | 12 |
| Combination (Prebiotic and Antibiotic) Saccharomyces boulardii AND Amoxicillin Clavulanate: Amoxicillin Clavulanate for 7 days (days 1 to 7; 875/125 mg 2 times daily at least 1 hour before meals) in addition to the dietary supplement Saccharomyces boulardii for 14 days (days 1 to 14; 500 mg, 2 times daily). | 12 |
| Control control group | 12 |
| Total | 49 |
Baseline characteristics
| Characteristic | Antibiotic (Amoxicillin Clavulanate) | Combination (Prebiotic and Antibiotic) | Prebiotic (Saccharomyces Boulardii) | Control | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 13 Participants | 12 Participants | 49 Participants |
| Age, Continuous | 27.4 years STANDARD_DEVIATION 6.6 | 34.2 years STANDARD_DEVIATION 11.4 | 31.6 years STANDARD_DEVIATION 9.9 | 27.2 years STANDARD_DEVIATION 4.3 | 30.1 years STANDARD_DEVIATION 8.8 |
| Region of Enrollment United States | 12 participants | 12 participants | 13 participants | 12 participants | 49 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 10 Participants | 5 Participants | 29 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 13 | 6 / 12 | 2 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Gastrointestinal Symptom Rating Scale
Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms
Time frame: Day 0
Population: Control participants were not assessed at this time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Gastrointestinal Symptom Rating Scale | 18.7 units on a scale | Standard Deviation 5.4 |
| Antibiotic (Amoxicillin Clavulanate) | Gastrointestinal Symptom Rating Scale | 18.7 units on a scale | Standard Deviation 3.8 |
| Combination (Prebiotic and Antibiotic) | Gastrointestinal Symptom Rating Scale | 17.3 units on a scale | Standard Deviation 2.4 |
Primary
Gastrointestinal Symptom Rating Scale
Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms
Time frame: Day 7
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Gastrointestinal Symptom Rating Scale | 23.2 Units on a scale | Standard Deviation 8.8 |
| Antibiotic (Amoxicillin Clavulanate) | Gastrointestinal Symptom Rating Scale | 26.9 Units on a scale | Standard Deviation 14.2 |
| Combination (Prebiotic and Antibiotic) | Gastrointestinal Symptom Rating Scale | 18.1 Units on a scale | Standard Deviation 3 |
| Control | Gastrointestinal Symptom Rating Scale | 19.3 Units on a scale | Standard Deviation 8.1 |
p-value: 0.026ANOVA
Primary
Gastrointestinal Symptoms Response Scale
Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms
Time frame: Day 21
Population: Participants analyzed were those with complete data at Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Gastrointestinal Symptoms Response Scale | 19.3 units on a scale | Standard Deviation 5.7 |
| Antibiotic (Amoxicillin Clavulanate) | Gastrointestinal Symptoms Response Scale | 18.4 units on a scale | Standard Deviation 5.8 |
| Combination (Prebiotic and Antibiotic) | Gastrointestinal Symptoms Response Scale | 16.5 units on a scale | Standard Deviation 2.9 |
| Control | Gastrointestinal Symptoms Response Scale | 15.8 units on a scale | Standard Deviation 2.3 |
Primary
Gastrointestinal Symptoms Response Score
Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms
Time frame: Day 14
Population: Participants analyzed were those with complete data at Day 14
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Gastrointestinal Symptoms Response Score | 19.3 units on a scale | Standard Deviation 5.1 |
| Antibiotic (Amoxicillin Clavulanate) | Gastrointestinal Symptoms Response Score | 20.3 units on a scale | Standard Deviation 5.9 |
| Combination (Prebiotic and Antibiotic) | Gastrointestinal Symptoms Response Score | 16.8 units on a scale | Standard Deviation 1.6 |
| Control | Gastrointestinal Symptoms Response Score | 18.1 units on a scale | Standard Deviation 4.3 |
Primary
Operational Taxonomic Units
Core Microbiome includes control samples and baseline samples (Day -7 and Day 0) for antibiotic, probiotic, and combination groups. Data for Core microbiome for individual arms are not available. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21
Time frame: Day 0 to Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Operational Taxonomic Units | 449.8 units | Standard Deviation 210.1 |
| Antibiotic (Amoxicillin Clavulanate) | Operational Taxonomic Units | 509.9 units | Standard Deviation 251.9 |
| Combination (Prebiotic and Antibiotic) | Operational Taxonomic Units | 461.1 units | Standard Deviation 228.2 |
| Control | Operational Taxonomic Units | 668.8 units | Standard Deviation 188.4 |
| Core Microbiome | Operational Taxonomic Units | 730.9 units | Standard Deviation 240.4 |
| Prebiotic (Saccharomyces Boulardii) During Treatment | Operational Taxonomic Units | 776.7 units | Standard Deviation 167.6 |
| Prebiotic (Saccharomyces Boulardii) After Treatment | Operational Taxonomic Units | 776.7 units | Standard Deviation 749.1 |
Primary
Prevalence of Escherichia in Stool
Control arm was not assessed as there was no intervention for this group. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21
Time frame: Day -7 to Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Prevalence of Escherichia in Stool | 0.1 percentage of total bacteria | Standard Deviation 0 |
| Antibiotic (Amoxicillin Clavulanate) | Prevalence of Escherichia in Stool | 4.5 percentage of total bacteria | Standard Deviation 0 |
| Combination (Prebiotic and Antibiotic) | Prevalence of Escherichia in Stool | 0.2 percentage of total bacteria | Standard Deviation 0 |
p-value: <0.05ANOVA
Primary
Prevalence of Escherichia in Stool
Control arm was not assessed as there was no intervention for this group. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21
Time frame: Day -7 to Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Prevalence of Escherichia in Stool | 0.0 percentage of total bacteria | Standard Deviation 0 |
| Antibiotic (Amoxicillin Clavulanate) | Prevalence of Escherichia in Stool | 2.9 percentage of total bacteria | Standard Deviation 0 |
| Combination (Prebiotic and Antibiotic) | Prevalence of Escherichia in Stool | 0.2 percentage of total bacteria | Standard Deviation 0 |
Primary
Prevalence of Escherichia in Stool
Control arm was not assessed as there was no intervention for this group. Before Treatment: Average of Day -7 and Day 0 During Treatment: Average of Day 3, Day 7, Day 10, Day 13 After Treatment: Average of Day 21
Time frame: Day -7 to Day 21
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prebiotic (Saccharomyces Boulardii) | Prevalence of Escherichia in Stool | 0.0 percentage of total bacteria | Standard Deviation 0 |
| Antibiotic (Amoxicillin Clavulanate) | Prevalence of Escherichia in Stool | 0.0 percentage of total bacteria | Standard Deviation 0 |
| Combination (Prebiotic and Antibiotic) | Prevalence of Escherichia in Stool | 0.1 percentage of total bacteria | Standard Deviation 0 |