Efficacy and Safety of BB-12 Supplemented Strawberry Yogurt For Healthy Children on Antibiotics (PLAY ON)

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common indications for probiotic treatment is the prevention of antibiotic-associated diarrhea (AAD). Unfortunately, many probiotic products used for AAD are not supported by rigorous independent research, and often results in non-evidence-based usage. The overarching objective is to move research forward for the most well-studied Bifidobacterium strain. The primary aim is to test the efficacy of high dose, BB-12-supplemented yogurt in preventing AAD, compared to yogurt without BB-12, in children receiving antibiotics. Other aims are to further assess the safety of yogurt supplemented with BB-12, and to carry out longitudinal community structure and gene expression analysis of fecal microbiota to evaluate the impact of high dose BB-12 in a pediatric population receiving antibiotics. The microbiota includes hundreds of species, and its disruption is hypothesized to be an important factor in the development of AAD.

Study Overview

• Status: Completed
• Conditions: Antibiotic-associated Diarrhea
• Intervention / Treatment: Biological: Bifidobacterium animalis subsp. lactis BB-12; Other: Control

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Department of Family Medicine, Research Division

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 8 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Child is between ages of 3-12 years
2. Caregiver has the ability to read, speak and write English or Spanish
3. Household has refrigerator for proper storage of drink
4. Household has telephone access
5. Enrollment must take place within 24 hours of starting antibiotics
6. Child was outpatient treated
7. Child was prescribed treatment with a penicillin or cephalosporin class antibiotic regimen for 7-10 days for a respiratory infection;

The following is a list (non-exhaustive) of inclusive antibiotics:

1. Amoxicillin
2. Augmentin (amoxicillin/clavulanate)
3. Ancef (cefazolin)
4. Cefadroxil
5. Cephalexin
6. Cephradine
7. Duricef (cefadroxil)
8. Keflex (cephalexin)
9. Kefzol (cefazolin)
10. Velosef (cephradine)
11. Ceclor (cefaclor)
12. Cefotan
13. Cefoxitin
14. Ceftin (cefuroxime)
15. Cefzil (cefprozil)
16. Lorabid (loracarbef)
17. Mefoxin (Cefoxitin)
18. Zinacef (cefuroxime)
19. Omnicef (cefdinir)
20. Suprax (cefixime)
21. Dicloxacillin
22. Pen-Vee K (penicillin)

Exclusion Criteria:

1. Developmental delays
2. Any chronic condition, such as diabetes or asthma, that requires medication
3. Prematurity, or born prior to 37 weeks gestation/of pregnancy
4. Congenital anomalies
5. Failure to thrive
6. Allergy to strawberry
7. Active diarrhea (diarrhea is defined in this study as three or more loose stools per day for two consecutive days)
8. Any other medicines used except anti-pyretic medicines (pro re nata concomitant medications are allowed)
9. Parental belief of lactose intolerance
10. History of heart disease, including valvulopathies or cardiac surgery, any implantable device or prosthetic
11. History of gastrointestinal surgery or disease
12. Milk-protein allergy
13. Allergy to any component of the product or the yogurt vehicle
14. Allergy or a hypersensitivity to the antibiotic prescribed by her/his provider

15. Allergy to any of the following medications:

    1. Tetracycline
    2. Erythromycin
    3. Trimethoprim
    4. Ciprofloxacin
16. blood oxygen saturation is less than 90% (if enrollment/baseline visit is completed in person and if the participant was prescribed antibiotics during a telemedicine visit)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BB-12; Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-supplemented yogurt	Biological: Bifidobacterium animalis subsp. lactis BB-12; Bifidobacterium animalis subsp. lactis BB-12-supplemented yogurt
Placebo Comparator: Control; Yogurt without Bifidobacterium animalis subsp. lactis BB-12	Other: Control; Yogurt without Bifidobacterium animalis subsp. lactis BB-12

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Diarrhea	Diarrhea is clinically defined as three or more loose stools per day for two consecutive days. This will be a dichotomous (yes or no) outcome of diarrhea.	14 days
Adverse Events	Number of reported adverse events over the duration of the study	Days 0-180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pediatric Quality-of-life Score	The PedsQL Measurement Measurement Model for the Pediatric Quality-of-Life Inventory. Based on the PedsQL form filled out by participants, the scores were translated using the PedsQL form guidelines: 0=100, 1=75, 2=50,3=25,4=0. The raw scores of participants were averaged after translation. The lowest possible score is 0 and the highest possible score is 100. A higher score indicates a healthier lifestyle.	7 days
Number of Events: Symptoms of Loose Stools, Constipation, Fever, Flatulence, Lack of Appetite, Pain, Rash, Vomiting, Cough, Earache, Nasal Congestion, Runny Nose, Sore Throat, Diarrhea.	This will be a dichotomous (yes or no) outcome of loose stools, constipation, fever, flatulence, lack of appetite, pain, rash, vomiting, cough, earache, nasal congestion, runny nose, sore throat.	14 days

Collaborators and Investigators

• Sponsor: Georgetown University
• Collaborators: University of Maryland, Baltimore; Penn State University
• Investigators: Principal Investigator: Daniel Merenstein, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2017
• Primary Completion (Actual): October 11, 2023
• Study Completion (Actual): October 11, 2023

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: 2016-1489 (Other Identifier: Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No