Mechanisms of Preventing Antibiotic-Associated Diarrhea and the Role for Probiotics

NCT03755765 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2018-07361R61AT009622-01A1
• Study Type: interventional
• Target: 66
• 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 (1)

• Level of Fecal Short-chain Fatty Acid (SCFA) Acetate

  Level of fecal short-chain fatty acid acetate (SCFA) after administration of amoxicillin clavulanate

  day 0 (post run-in), 7, 14, 21, 30

Secondary Outcomes (2)

• Level of Fecal SCFA Propionate

  day 0 (post run-in), 7, 14, 21, 30

• Level of Fecal SCFA Butyrate

  day 0 (post run-in), 7, 14, 21, 30

Other Outcomes (4)

• Change in Community Diversity (Shannon Diversity Index) From Pre run-in Baseline

  day 0 (pre run-in), 7, 14, 21, 30

• Change in Community Diversity (Shannon Diversity Index) From Post run-in Baseline

  day 0 (post run-in), 7, 14, 21, 30

• Bray-Curtis Dissimilarity

  day 0, 7, 14, 21, 30

Study Arms (2)

Control

PLACEBO COMPARATOR

Yogurt without Bifidobacterium animalis subsp. lactis BB-12 (BB-12) and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

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

BB-12

EXPERIMENTAL

Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt and Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

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

Interventions

Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet DRUG

Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet

Also known as: Augmentin

BB-12; Control

BB-12 BIOLOGICAL

Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt

BB-12

Control OTHER

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

Control

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 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 What Not to Eat 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

Sponsors & Collaborators

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

Study Sites (1)

Georgetown University Department of Family Medicine

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

Location

Related Publications (1)

• Merenstein D, Fraser CM, Roberts RF, Liu T, Grant-Beurmann S, Tan TP, Smith KH, Cronin T, Martin OA, Sanders ME, Lucan SC, Kane MA. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome. Nutrients. 2021 Aug 17;13(8):2814. doi: 10.3390/nu13082814.

  PMID: 34444974 RESULT

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: Daniel Merenstein, MD
• Organization: Department of Family Medicine, Georgetown University Medical Center

djm23@georgetown.edu

202-687-2745

Study Officials

• Daniel Merenstein, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

• Claire Fraser, PhD

  University of Maryland, Baltimore

  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: November 18, 2018
• First Posted: November 28, 2018
• Study Start: July 23, 2019
• Primary Completion: January 8, 2020
• Study Completion: January 8, 2020
• Last Updated: February 17, 2023
• Results First Posted: February 17, 2023

Record last verified: 2023-02

Locations

US (1)