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| Name | Class |
|---|---|
| Lifeway Foods, Inc. | INDUSTRY |
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The purpose of this study is to determine the effectiveness of commercially available kefir on preventing antibiotic-associated diarrhea compared to placebo in children ages 1-5.
Diarrhea is a common and costly disease of children in the United States. Children less than 5 years of age experience 20-35 million episodes of diarrhea per year. These episodes lead to 2-3.5 million physician visits (which account for 10% of all visits), more than 200,000 hospitalizations (13% of hospital admissions in children less than 5 years), and 325-425 deaths annually. In 1991, the outpatient costs of treating diarrhea for children under age 3 were calculated at 0.6-1 billion dollars per year.
Acute diarrhea in young children is almost always caused by infections or antibiotics. The rate of diarrhea associated with antibiotic usage is 20-35%, with children 3-36 months receiving on average 2-3 antibiotic prescriptions per year. Studies have shown that diarrhea due to either antibiotics or infections is caused by disturbances of the microflora of the gastrointestinal tract.
The current treatment for diarrhea in young children is oral rehydration, which is used to treat dehydration but plays no role in prevention. Probiotics are live microorganisms which, when administered in sufficient amounts, may improve health. Probiotics have the potential to treat and prevent diarrhea by improving the intestinal flora when disturbed by events such as antibiotics. Important to their use is that they are of human origin, survive passage through the gut, and are safe in very large dosages.
Studies have examined the potential health benefits of probiotics in the prevention and treatment of both antibiotic and infectious diarrhea. The probiotics have generally been given as supplements or pills. In placebo controlled randomized studies using these techniques, probiotics have generally been shown to decrease antibiotic associated diarrhea by 15-25% over placebo. Other studies have enrolled children with acute diarrhea, generally from rotavirus, and found a 30-50% cure rate in the probiotic group over placebo.
Kefir, available in the United States, is a milk product derived by the action of ten probiotics. A daily dose of 10^6-10^9 colony forming units of probiotics has been studied and recommended for health benefits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Kefir | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Kefir | Other | The intervention was Kefir,a drink that is commercially available in the United States. The following probiotics are present in the Kefir: Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. Parents were asked to ensure that their enrolled child consumed at least half of the bottle (150mL) everyday. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Participants With Diarrhea by Parental Report | The primary outcome was the incidence of participants receiving antibiotics with diarrhea during the 14-day follow-up period, as determined by parental report. | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools. Outcomes assessed by parental report via daily diary and phone follow-ups with study research assistants on days 0, 5, 10, and 15. | 14 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daniel Merenstein, MD | Georgetown University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgetown University Deptartment of Family Medicine | Washington D.C. | District of Columbia | 20007 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19652108 | Result | Merenstein DJ, Foster J, D'Amico F. A randomized clinical trial measuring the influence of kefir on antibiotic-associated diarrhea: the measuring the influence of Kefir (MILK) Study. Arch Pediatr Adolesc Med. 2009 Aug;163(8):750-4. doi: 10.1001/archpediatrics.2009.119. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | 150mL per day, administered orally for 10 consecutive days. Placebo was heat-treated to kill all cultures. |
| FG001 | Kefir | 150mL per day, administered orally for 10 consecutive days. Active kefir contained probiotics Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | 150mL per day, administered orally for 10 consecutive days. Placebo was heat-treated to kill all cultures. |
| BG001 | Kefir | 150mL per day, administered orally for 10 consecutive days. Active kefir contained probiotics Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Participants With Diarrhea by Parental Report | The primary outcome was the incidence of participants receiving antibiotics with diarrhea during the 14-day follow-up period, as determined by parental report. | Prior estimates of the sample size showed that 62 per group would have 80% power for detecting a difference of 20% in the rates of diarrhea. This was based on the placebo group having a 10% (which is consistent with published literature) rate of diarrhea. Analysis performed used the intention to treat and no imputation was required. | Posted | Number | 95% Confidence Interval | Percentage of participants | 14 days |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 150mL per day, administered orally for 10 consecutive days. Placebo was heat-treated to kill all cultures. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| emesis | Gastrointestinal disorders | Non-systematic Assessment |
We did not assess or culture stools for the presence of pathogenic organisms. We did not independently examine children; we relied on parental/patient-oriented outcomes. Our population was generally very healthy. We did not assess probiotic dosages.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniel Merenstein, MD | GEORGETOWN UNIVERSITY | 202-687-2745 | djm23@georgetown.edu |
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| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D000070716 | Kefir |
| ID | Term |
|---|---|
| D000088082 | Fermented Beverages |
| D001628 | Beverages |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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|
| Placebo | Other | The intervention was Kefir, a drink that is commercially available in the United States. The following probiotics are present in active Kefir: Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. The placebo group was heat-treated to kill all cultures. Parents were asked to ensure that their enrolled child consumed at least half of the bottle (150 mL)everyday. |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | 150mL per day, administered orally for 10 consecutive days. Placebo was heat-treated to kill all cultures. |
|
|
|
| Secondary | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools | Incidence of Vomiting, Stomach Pain, Constipation, Runny Nose, Cough, Earaches, Fever, Irritability, Lethargy, and Loose Stools. Outcomes assessed by parental report via daily diary and phone follow-ups with study research assistants on days 0, 5, 10, and 15. | Posted | Number | 95% Confidence Interval | Percentage of participants | 14 days |
|
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|
| 0 |
| 64 |
| 1 |
| 64 |
| EG001 | Kefir | 150mL per day, administered orally for 10 consecutive days. Active kefir contained probiotics Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and 1 yeast, Saccharomyces florentinus. | 0 | 61 | 1 | 61 |
| constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D043302 |
| Cultured Milk Products |
| D008892 | Milk |
| D000074421 | Fermented Foods |
| D003611 | Dairy Products |
| D005502 | Food |
| D019602 | Food and Beverages |
| constipation |
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| runny nose |
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| cough |
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| earaches |
|
| fever |
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| irritability |
|
| lethargy |
|
| loose stools |
|