Safety of Lactobacillus Reuteri in Healthy Volunteers

Study Overview
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Brief Summary
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This is a phase one study to assess the safety of daily dosing of Lactobacillus reuteri in healthy adults in Peru. It is conducted as a preliminary study in support of a clinical trial to assess safety and efficacy of Lactobacillus reuteri versus placebo 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).

Official Title
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Phase 1: Safety of Lactobacillus Reuteri in Healthy Volunteers

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults 18-65 with no exclusion criteria Subject is a male or, if the subject is female and of childbearing potential then she must have a negative serum or urine pregnancy test result within 48 hours of initiating study preparations and agree to use an acceptable method of contraception. Acceptable methods of contraception include depot forms of progesterone containing therapies or an intrauterine device (IUD). Exclusion Criteria: 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 (corticosteroids, methotrexate) by any household member Presence of a serious congenital anomaly or chronic medical condition that would contraindicate participation in any household member, including history of gastrointestinal surgery, chronic gastrointestinal illness, abnormal intestinal anatomy, or abnormal bowel functionality Allergy to penicillin or cephalosporins History of antibiotic use in the last 30 days Use of probiotic products within the past 90 days History of diarrheal illness within the past 30 days Presence of fever or a pre-existing adverse event monitored in the study Positive results on serum diagnostic tests for antibodies to HIV, Hepatitis B core antigen, and Hepatitis C.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: 1<br>Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period | Biological: Lactobacillus reuteri<br>* Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period<br>* Other names: BioGaia Probiotic Drops;|
| Placebo Comparator: 2<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 | Other: Placebo<br>* 5 drops of the oil vehicle used in manufacturing the Lr suspension, given once daily for a five-day study period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Positive Blood Culture for L. Reuteri | To assess association between administration of Lactobacillus reuteri (Lr) strain DSM 17938 and abnormal lab values (CBC, BUN, Creatinine, AST, ALT, blood culture). | participants were followed for an average of 36 days | 
| Mean Daily Temperature | Measured daily during 5 days of study product administration | 5 days of study product administration | 
| Leukocyte Count on Day 5 |  | Measured on day 5 | 
| Serum Alanine Aminotransferase (ALT) in Female Participants |  | Day 5 | 
| Serum ALT in Males |  | Day 5 | 
| Serum Aspartate Aminotransferase (AST) in Females |  | Day 5 | 
| Serum AST in Males |  | Day 5 | 
| Blood Urea Nitrogen |  | Day 5 | 
| Serum Creatinine |  | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With at Least One PCR Positive Stool Specimen |  | Average of 36 day follow up period | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported |  | Day 0 through 6 weeks after Day 0 | 
| Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported |  | Day 0 through 6 weeks after Day 0 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, lactobacillus, reuteri, none (safety only)