Children
Conditions
Brief summary
The investigators believe a readily available drink containing a high dose of probiotics has the potential to improve compliance through many of these mechanisms. This product also has the potential to positively impact the health of children and adults around the world, as yogurt will likely be more appealing to both children and their parents for long term consumption than pharmaceutical-like preparations. In addition to the benefits associated with the consumption of probiotics, there is an increased health benefit from consuming yogurt, a nutrient dense food. More specifically, the rationale for this Phase I study is to determine safety of this yogurt drink and comply with FDA recommendations pertaining to an Investigational New Drug application. The investigators hypothesize that BB-12 is safe in generally healthy children ages 1-5 years.
Detailed description
Probiotics are live microorganisms that, when administered in sufficient amounts, may improve health. A common use for probiotics is in addressing gastrointestinal issues, such as antibiotic-associated diarrhea (AAD). As an alternative to supplements, probiotics are also included as ingredients in fermented dairy products to produce functional foods, which are foods providing health benefits beyond their nutritional value. Yogurt, for example, is a fermented milk product often considered a functional food. One of the most commonly used probiotics is Bifidobacterium animalis ssp. lactis (BB-12). Our Primary Aim in Years 1-2 is to conduct a pediatric randomized controlled study to establish the safety of BB-12 fortified yogurt in children. Our Secondary Aims are to examine the fecal microbiota of children prior to, during and following consumption of probiotics. This study will evaluate whether a well-defined, probiotic-containing yogurt can safely be used as an effective delivery vehicle for probiotics. This study is important to help advance probiotic research forward in a systematic, well-accepted manner. Our long-term goal is to create yogurt with sufficient probiotic dosages to positively impact many different aspects of childhood and adult health.
Interventions
DRUGBB-12 supplemented strawberry yogurt
Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12 (BB-12) probiotic supplemented yogurt, 4 ounces taken orally for 10 days
OTHERStrawberry flavored yogurt
Placebo, strawberry yogurt, 4 ounces taken orally for 10 days
Sponsors
Penn State University
Georgetown University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
Yes
Inclusion criteria
for parents/caregivers are: 1. Ability to read, speak and write English or Spanish 2. Access to a refrigerator for proper storage of drink 3. Telephone access Inclusion criteria for children are: 1\. Are between the ages of 1 and 5 years
Exclusion criteria
1. Developmental delays 2. Any chronic condition, such as diabetes or asthma, that requires medication 3. Prematurity, birth weight \< 2,500 grams 4. Congenital anomalies 5. Failure to thrive 6. Allergy to strawberry 7. Active diarrhea (defined as three or more loose stools for two consecutive days) 8. Any other medicines used except anti-pyretic medicines (to reduce fever) \[excluding as needed medications\] 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. During the baseline physical exam, have an oxygen saturation rate \<96% and respiratory and pulse rate outside the normal range per their age. Parents/caregivers will also be asked to refrain from giving their child any probiotic foods or supplements during the entire 2 weeks of the active intervention period, and 2 weeks before day 1 of starting the yogurt. Parents will be supplied with a list of products to avoid.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events | Days 0-180 | The primary outcome is to assess the safety of BB-12® yogurt when consumed by generally healthy children. To achieve this aim, data on adverse events will be collected from diaries; calls to the 24-hour advice line; and research assistant phone calls on days 6, 11, 15 and 180, ±2 days. All adverse events will be tabulated by type and charted over time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Composition of the Gut Microbiota | 90 days | Relative abundance of operational taxonomic units (OTU) classified at the phylum level |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BB-12® Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12®-supplemented yogurt | 29 |
| Control yogurt cultured with starter YF-L702 | 31 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Control | BB-12® |
|---|---|---|---|
| Age, Categorical <=18 years | 60 Participants | 31 Participants | 29 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Child Attends Daycare No | 23 Participants | 14 Participants | 9 Participants |
| Child Attends Daycare Yes | 37 Participants | 17 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 26 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Parent's Marital Status Divorced | 2 Participants | 2 Participants | 0 Participants |
| Parent's Marital Status Married/Living with partner | 54 Participants | 28 Participants | 26 Participants |
| Parent's Marital Status Single | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 17 Participants | 21 Participants |
| Sex: Female, Male Female | 31 Participants | 18 Participants | 13 Participants |
| Sex: Female, Male Male | 29 Participants | 13 Participants | 16 Participants |
| Smoker in Household-Yes | 3 Participants | 3 Participants | 0 Participants |
| Total Household Income $100,001-$150,000 | 16 Participants | 8 Participants | 8 Participants |
| Total Household Income >$150,000 | 12 Participants | 6 Participants | 6 Participants |
| Total Household Income $15,000-$30,000 | 3 Participants | 1 Participants | 2 Participants |
| Total Household Income $30,001-$75,000 | 16 Participants | 10 Participants | 6 Participants |
| Total Household Income $75,001-$100,000 | 12 Participants | 6 Participants | 6 Participants |
| Total Household Income No response | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 29 | 22 / 31 |
| serious Total, serious adverse events | 3 / 29 | 0 / 31 |
Outcome results
Primary
Number of Adverse Events
The primary outcome is to assess the safety of BB-12® yogurt when consumed by generally healthy children. To achieve this aim, data on adverse events will be collected from diaries; calls to the 24-hour advice line; and research assistant phone calls on days 6, 11, 15 and 180, ±2 days. All adverse events will be tabulated by type and charted over time.
Time frame: Days 0-180
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BB-12® | Number of Adverse Events | During intervention (day 0-10) | 61 Number of AE reported |
| BB-12® | Number of Adverse Events | Post-intervention (day 11-180) | 52 Number of AE reported |
| Control | Number of Adverse Events | During intervention (day 0-10) | 35 Number of AE reported |
| Control | Number of Adverse Events | Post-intervention (day 11-180) | 38 Number of AE reported |
Secondary
Overall Composition of the Gut Microbiota
Relative abundance of operational taxonomic units (OTU) classified at the phylum level
Time frame: 90 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BB-12® | Overall Composition of the Gut Microbiota | Bacteroidetes | 14.7 relative abundance (%) |
| BB-12® | Overall Composition of the Gut Microbiota | Proteobacteria | 1.6 relative abundance (%) |
| BB-12® | Overall Composition of the Gut Microbiota | Actinobacteria | 11.1 relative abundance (%) |
| BB-12® | Overall Composition of the Gut Microbiota | Verrucomicrobia | 0.7 relative abundance (%) |
| BB-12® | Overall Composition of the Gut Microbiota | Firmicutes | 71.7 relative abundance (%) |
| Control | Overall Composition of the Gut Microbiota | Verrucomicrobia | 1.0 relative abundance (%) |
| Control | Overall Composition of the Gut Microbiota | Firmicutes | 74.1 relative abundance (%) |
| Control | Overall Composition of the Gut Microbiota | Bacteroidetes | 11.6 relative abundance (%) |
| Control | Overall Composition of the Gut Microbiota | Actinobacteria | 11.9 relative abundance (%) |
| Control | Overall Composition of the Gut Microbiota | Proteobacteria | 1.4 relative abundance (%) |