Safety of Lactobacillus Reuteri in Healthy Volunteers

Phase 1

Completed

Brief Summary: 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: 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).

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
1	Lactobacillus reuteri	Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period
2	Placebo	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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 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 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 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 Subjective Fever Reported	Day 0 through 6 weeks after Day 0
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 Myalgia Reported	Day 0 through 6 weeks after Day 0