Safety of Lactobacillus Reuteri (L. Reuteri) in Healthy Adults

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of the probiotic Lactobacillus reuteri (LR) in healthy adult patients. Patients will be randomized to receive either LR or placebo orally each day for a total of 60 doses. The effects on fecal bacteria, circulating white blood cell receptors and inflammatory cytokine profiles will be measured.

Detailed Description
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Lactobacillus reuteri oil drops are a natural product containing Lactobacillus reuteri (LR), which has traditionally been used for the establishment and maintenance of a well-functioning gastro-intestinal (GI) tract micro flora and prevention and treatment of mild diarrhea associated with GI-tract infections. The oil drops contain a dietary supplement of Lactobacillus reuteri DSM 17938. The patients will receive 5 drops (10^8 live organisms) by mouth daily for 60 days. Daily administration will include 5 drops (5x10^8) of L. reuteri or placebo daily for two months. During this time,circulating peripheral blood mononuclear cell (PBMC) toll-like receptor-2 and -4 levels will be measured, along with PBMC cytokine production levels in vitro. Fecal DGGE analysis(with sequencing of bacterial rDNA) will be completed identifying changes in fecal microbiota. Inflammation in the gut will also be assessed by fecal calprotectin assay (ELISA). The time on study treatment is 2 months, with 4 months observation, for a total of 6 months. There will be 7 required visits, during which, we will assess safety and immune system effects.

Official Title
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Phase I Safety and Tolerance of Lactobacillus Reuteri in Adults

Conditions
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Colic, Gastrointestinal Tract Infections

Intervention / Treatment
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* Biological: L. reuteri
* Biological: Sunflower Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Adults (18 - 60 years old) No other recognized illness Exclusion Criteria: Pregnancy or breastfeeding Patient taking immunosuppressive medications, including oral corticosteroids Positive result of HIV, Hepatitis B, and/or Hepatitis C test Abnormal lab test results Gastrointestinal related diseases and surgeries Patients with an allergy to antibiotics Presence of fever or a pre-existing adverse event monitored in the study No more than two study participants in one household Use of probiotics in the last 90 days Diarrheal illness within the past 30 days Recent or current use of oral antibiotics /anti-fungals(in the past 2 weeks) Current use of oral laxatives Chronic alcohol use or more than 1 drink per day Subjects with implanted prosthetic devices including prosthetic heart valves Known sensitivity to sunflower oil or products containing linolenic/oleic acids Will require that subject not take any other probiotic-containing products, including yogurt supplemented with probiotics during the 6-month period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: L. reuteri<br>Lactobacillus reuteri oil drops are a natural product containing Lactobacillus reuteri (LR), which has traditionally been used for the establishment and maintenance of a well-functioning gastro-intestinal (GI) tract microflora and prevention and treatment of mild diarrhea associated with GI-tract infections, travel or antibiotic treatment. The oil drops contain a dietary supplement of Lactobacillus reuteri DSM 17938. | Biological: L. reuteri<br>* The oil drops contains 10^8 CFU (colony forming units). As suggested by the manufacturer in the Certificate of Analysis the daily dose given to each patient will be 5 x 10^8 CFU/ 5 drops. The dose given is within the release limit which is greater than 2 x 10^8 CFU/ 5 drops and less than 8 x 10^8 CFU/ 5 drops.<br>* Other names: BioGaia Drops;|
| Placebo Comparator: Sunflower Oil<br>Placebo will be the equivalent number of drops of suspended sunflower oil (without LR), provided by Biogaia. | Biological: Sunflower Oil<br>* As suggested by the manufacturer in the Certificate of Analysis the daily dose given to each patient will be 5 x 10^8 CFU/ 5 drops.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment of adults with probiotic (health-promoting bacteria) LR, will be safe and well-tolerated. |  | 8/1/2009 - 7/1/2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if LR treatment affects circulating levels of pro-inflammatory and anti-inflammatory cytokines, along with expression levels of toll like receptors (TLRs)-2 and -4 in circulating peripheral blood mononuclear cells. |  | 4/1/2009-7/1/2009 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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L. reuteri, Cytokines, Toll like receptors, Healthy Adults, Probiotics