Mechanisms of Probiotics and Antibiotic-Associated Diarrhea

NCT04414722 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-2431R33AT009622
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

The focus of the study is to better understand the mechanisms causing antibiotic-associated diarrhea (AAD) and how probiotics may prevent some of the iatrogenic effects of antibiotic medications. One of the most common indications for probiotics is for prevention of antibiotic-associated diarrhea. Clinically, different probiotic strains have demonstrated the ability to prevent AAD; however, the mechanism of action behind this effect has not been elucidated. Data from several studies suggest that antibiotic-induced disruption of commensal bacteria in the colon results in a significant (up to 50%) reduction in short chain fatty acid (SCFA) production and a concomitant reduction in Na-dependent fluid absorption resulting in AAD. Probiotics have been shown to ameliorate a variety of gastrointestinal disease states and thus, the study investigators hypothesize that administration of a probiotic yogurt will protect against the development of AAD.

Conditions

Antibiotic-associated Diarrhea

Outcome Measures

Primary Outcomes (2)

• Change From Baseline Levels of Fecal Short-chain Fatty Acid (With a Particular Focus on Acetate)

  Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)

  day 7

• Change From Baseline Levels of Fecal Short-chain Fatty Acid (With a Particular Focus on Acetate)

  Change from baseline levels of fecal short-chain fatty acid (with a particular focus on acetate)

  day 30

Secondary Outcomes (2)

• Percentage Change in Baseline Diversity of Bacterial Species in Fecal Microbiota

  day 7

• Percentage Change in Baseline Diversity of Bacterial Species in Fecal Microbiota

  day 14

Other Outcomes (2)

• Change From Baseline Levels of Fecal Short-chain Fatty Acid (With a Particular Focus on Acetate)

  day 14

• Change From Baseline Levels of Fecal Short-chain Fatty Acid (With a Particular Focus on Acetate)

  day 21

Study Arms (5)

Concurrent control yogurt and amoxicillin-clavulanate

PLACEBO COMPARATOR

Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Other: Control Yogurt

Control yogurt taken 4 hours after amoxicillin-clavulanate

PLACEBO COMPARATOR

Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Other: Control Yogurt

Concurrent BB-12 yogurt and amoxicillin-clavulanate

ACTIVE COMPARATOR

Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt and amoxicillin-clavulanate 875 mg-125 mg oral tablet, taken at the same time

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Biological: BB-12

BB-12 yogurt taken 4 hours after amoxicillin-clavulanate

ACTIVE COMPARATOR

Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt taken 4 hours after amoxicillin-clavulanate 875 mg-125 mg oral tablet

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet; Biological: BB-12

Amoxicillin-clavulanate

OTHER

Amoxicillin-clavulanate 875 mg-125 mg oral tablet

Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

Interventions

Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet DRUG

Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

Also known as: Augmentin, Amoxicillin/clavulanic acid

Amoxicillin-clavulanate; BB-12 yogurt taken 4 hours after amoxicillin-clavulanate; Concurrent BB-12 yogurt and amoxicillin-clavulanate; Concurrent control yogurt and amoxicillin-clavulanate; Control yogurt taken 4 hours after amoxicillin-clavulanate

BB-12 BIOLOGICAL

Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt

Also known as: Bifidobacterium animalis subsp. lactis, BB-12

BB-12 yogurt taken 4 hours after amoxicillin-clavulanate; Concurrent BB-12 yogurt and amoxicillin-clavulanate

Control Yogurt OTHER

Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12)

Concurrent control yogurt and amoxicillin-clavulanate; Control yogurt taken 4 hours after amoxicillin-clavulanate

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has the ability to read, speak, and write in English
• Has a refrigerator (for proper storage of the study yogurt)
• Has reliable telephone access
• Is between ages of 18-65 years
• Agree to refrain from eating yogurts, yogurt drinks, and other foods specified in the provided list
• Agree to collect stool samples and participate in follow-up calls as specified

You may not qualify if:

• Diabetes or asthma that requires medication
• Allergy to strawberry
• Active diarrhea (three or more loose stools per day for two consecutive days)
• Any gastrointestinal (or digestive tract) medications, i.e. medicines for irritable bowel syndrome, gastroesophageal (acid) reflux disease, inflammatory bowel disease, etc.
• History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic
• History of gastrointestinal surgery or disease
• Lactose intolerance that prevents participant from eating yogurt
• Allergy to milk-protein
• Allergy to any component of the product or the yogurt vehicle
• Allergy to penicillin or cephalosporin class antibiotics
• Allergy to any of the following medications: a) Penicillin; b) Erythromycin; c) Tetracycline; d) Trimethoprim; e) Ciprofloxacin
• Women who are breastfeeding, pregnant, or planning to become pregnant during the study
• Was a participant in the "YOBIOTIC" study

Sponsors & Collaborators

• Georgetown University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator
• University of Maryland, Baltimore: collaborator
• Penn State University: collaborator

Study Sites (1)

Georgetown University Department of Family Medicine

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

Amoxicillin-Potassium Clavulanate Combination

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dan Merenstein, Director of Research Programs
• Organization: Dept. of Family Medicine, Georgetown University Medical Center

djm23@georgetown.edu

202-687-1600

Study Officials

• Daniel Merenstein, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research Programs

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 4, 2020
• Study Start: January 1, 2021
• Primary Completion: May 1, 2023
• Study Completion: May 1, 2023
• Last Updated: February 25, 2025
• Results First Posted: February 25, 2025

Record last verified: 2025-02

Locations

US (1)