Safety of Lactobacillus Reuteri in Healthy Children Ages 2 to 5 Years in Peru

Study Overview
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Brief Summary
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This is a Phase 1 study to assess the safety and tolerability of Lactobacillus reuteri (Lr) strain DSM 17938 in healthy children in Peru. It is a preliminary study in support of a clinical trial to assess safety and efficacy of L. reuteri for treatment of pediatric diarrhea in Peru.

Detailed Description
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This is a phase I blinded randomized study of the safety and tolerability of Lactobacillus reuteri DSM 17938 given daily for a period of five consecutive days. Upon enrollment subjects will be randomized to one of two treatment groups in a ratio of treatment to placebo of 2:1. Subjects will be randomized to receive either: A. Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period that corresponds to a dose of the closely related L. reuteri ATCC 55730 strain that has shown to be therapeutic for infantile colic. The strain used in this study (DSM 17938) has been cured of an antibiotic resistance plasmid found in the original BioGaia strain (L. reuteri ATCC 55730). B. Placebo oil preparation, administered as 5 drops of the oil vehicle used in manufacturing the Lr suspension, given once daily for a five-day study period (BioGaia AB, Stockholm, Sweden). In the first 30 subjects randomized, administration of each dose of the study preparation drops (A or B above) will be immediately followed by offering 2 ounces of flavored PediaSure ® (Abbott Laboratories) nutritional supplement to each child. The second 30 subjects enrolled will not be offered PediaSure ® after product administration. This format will also allow us to assess the impact of concurrent administration of a buffering non-lactose containing formula with prebiotic nutritional properties on intestinal colonization with L. reuteri by PCR.

Official Title
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Safety of Lactobacillus Reuteri in Healthy Children Ages 2 to 5 Years in Peru

Conditions
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Healthy

Intervention / Treatment
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* Biological: Lactobacillus reuteri
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 2-5 years with no exclusion criteria Exclusion Criteria: 1) No enrollment of family members in households where any of the following are present: Another study participant in the household Pregnancy or current breastfeeding by any household member Presence of an infant under age 6 months living in the household Presence of immune suppressed individuals or use of immunosuppressive agents (including but not limited to corticosteroids and methotrexate, etc.) by any household member Presence of a serious congenital anomaly or chronic medical condition that in the opinion of the investigators would contraindicate participation in any household member, including history of gastrointestinal surgery, chronic gastrointestinal illness, abnormal intestinal anatomy, or abnormal bowel functionality 2) Allergy to penicillin or cephalosporins or gentamicin 3) History of antibiotic use in the last 30 days 4) Use of probiotic products within the past 90 days, including masato (local product with fermenting bacteria) and yogurt products containing live bacterial cultures. 5) History of diarrheal illness within the past 30 days 6) Presence of fever or a pre-existing adverse event monitored in the study 7) Positive results on serum diagnostic tests for antibodies to HIV. Testing for Hepatitis B core antigen, and Hepatitis C is not necessary in children as in adults, since there is universal vaccination for Hepatitis B among children in this community, and both forms of hepatitis are rare and largely asymptomatic in this age group. 8) Presence of severe anemia, defined as serum hemoglobin < 8 gm/dL 9) Out of range laboratory values for tests monitored as potential adverse events, as described in Appendix 2, B. LABORATORY VALUES, and detected based on Day 0 blood test results. However, subjects will only be excluded based on serum hemoglobin if they meet exclusion criterion 8. 10) Pre-enrollment stool sample (collected within 14 days of Day 1 of the study) is positive for L. reuteri by PCR.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactobacillus<br>Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period that corresponds to a dose of the closely related L. reuteri ATCC 55730 strain that has shown to be therapeutic for infantile colic. The strain used in this study (DSM 17938) has been cured of an antibiotic resistance plasmid found in the original BioGaia strain (L. reuteri ATCC 55730). | Biological: Lactobacillus reuteri<br>* Probiotic<br>* Other names: BioGaia Probiotic Drops;|
| Placebo Comparator: Placebo<br>Placebo oil preparation, administered as 5 drops of the oil vehicle used in manufacturing the Lr suspension, given once daily for a five-day study period (BioGaia AB, Stockholm, Sweden). | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Blood Culture for L Reuteri |  | Participants are followed an average of 36 days | 
| Mean Daily Temperature | Mean of body temperatures recorded on study days listed, averaged across all participants at all time points | Study days 1-5, 8,12, 15, 18, 28, and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Focus, safety