Effects of S. Boulardii and Amoxicillin/Clavulanate on Gut Microbiota

Open Label, Randomized Pilot Study to Examine The Effects of the Probiotic Saccharomyces Boulardii, the Antibiotic Amoxicillin/Clavulanate and the Combination on the Gut Microbiota of Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Dietary supplement: Saccharomyces boulardii; Drug: Amoxicillin Clavulanate

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control
Active Comparator: prebiotic (Saccharomyces boulardii); 500 mg, 2 times daily for 14 days	Dietary supplement: Saccharomyces boulardii; 500 mg, 2 times daily for 14 days
Active Comparator: antibiotic (Amoxicillin Clavulanate); 875/125 mg 2 times daily at least 1 hour before meals for 7 days	Drug: Amoxicillin Clavulanate; 875/125 mg 2 times daily at least 1 hour before meals for 7 days
Active Comparator: combination (prebiotic and antibiotic); 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).	Dietary supplement: Saccharomyces boulardii; 500 mg, 2 times daily for 14 days; Drug: Amoxicillin Clavulanate; 875/125 mg 2 times daily at least 1 hour before meals for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal Symptom Rating Scale	Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms	Day 0
Gastrointestinal Symptom Rating Scale	Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms	Day 7
Gastrointestinal Symptoms Response Score	Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms	Day 14
Gastrointestinal Symptoms Response Scale	Mean Gastrointestinal Symptom Rating Scale scores Range from 15 to 90 Increasing score means increasing symptoms	Day 21
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	Day -7 to Day 21
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	Day 0 to Day 21

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Biocodex
• Investigators: Principal Investigator: Ciaran P Kelly, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Kelly CP, Chong Nguyen C, Palmieri LJ, Pallav K, Dowd SE, Humbert L, Seksik P, Bado A, Coffin B, Rainteau D, Kabbani T, Duboc H. Saccharomyces boulardii CNCM I-745 Modulates the Fecal Bile Acids Metabolism During Antimicrobial Therapy in Healthy Volunteers. Front Microbiol. 2019 Mar 4;10:336. doi: 10.3389/fmicb.2019.00336. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (Estimate): November 17, 2011

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: March 3, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: probiotic; antibiotic; gut microbiome; gut microbiota; antibiotic-associated diarrhea; human Gut Microbiota; intestinal bacterial overgrowth
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination
• Other Study ID Numbers: 2011P000389