Healthy
Conditions
Keywords
probiotics, lactobacillus, reuteri, none (safety only)
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).
Interventions
OTHERPlacebo
5 drops of the oil vehicle used in manufacturing the Lr suspension, given once daily for a five-day study period
BIOLOGICALLactobacillus reuteri
Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Johns Hopkins Bloomberg School of Public Health
Asociacion Benefica Prisma
Tulane University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Creatinine | 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 |
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Number of Subjects With at Least One PCR Positive Stool Specimen | Average of 36 day follow up period |
Countries
Peru
Participant flow
Recruitment details
Potential subjects were inoformed of the study in community meetings in Santa Clara, Peru. Interested individuals were enrolled at the study clinic between Feb. 23, 2010 and April 2, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Lactobacillus Group Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period | 30 |
| Placebo Group 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 | 15 |
| Total | 45 |
Baseline characteristics
| Characteristic | Placebo Group | Lactobacillus Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 30 Participants | 45 Participants |
| Age, Continuous | 32.3 years STANDARD_DEVIATION 2.3 | 39.1 years STANDARD_DEVIATION 2 | 36.8 years STANDARD_DEVIATION 1.8 |
| Gender Female | 9 Participants | 23 Participants | 32 Participants |
| Gender Male | 6 Participants | 7 Participants | 13 Participants |
| Region of Enrollment Peru | 15 participants | 30 participants | 45 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 27 / 30 | 13 / 15 |
| serious Total, serious adverse events | 0 / 30 | 0 / 15 |
Outcome results
Primary
Blood Urea Nitrogen
Time frame: Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Blood Urea Nitrogen | 22.4 mg/dl | Standard Deviation 7 |
| Placebo Group | Blood Urea Nitrogen | 19.3 mg/dl | Standard Deviation 5.4 |
Primary
Leukocyte Count on Day 5
Time frame: Measured on day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Leukocyte Count on Day 5 | 6936 cells per cubic millimeter | Standard Deviation 1331 |
| Placebo Group | Leukocyte Count on Day 5 | 7893 cells per cubic millimeter | Standard Deviation 1168 |
Primary
Mean Daily Temperature
Measured daily during 5 days of study product administration
Time frame: 5 days of study product administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Mean Daily Temperature | 36.02 Degrees Celcius | Standard Deviation 0.5 |
| Placebo Group | Mean Daily Temperature | 36.04 Degrees Celcius | Standard Deviation 0.5 |
Primary
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).
Time frame: participants were followed for an average of 36 days
Population: 2:1 randomization Lactbacillus:placebo using a randomizatin table as specified in the protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Number of Participants With a Positive Blood Culture for L. Reuteri | 0 participants |
| Placebo Group | Number of Participants With a Positive Blood Culture for L. Reuteri | 0 participants |
Primary
Serum Alanine Aminotransferase (ALT) in Female Participants
Time frame: Day 5
Population: limited to females
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Serum Alanine Aminotransferase (ALT) in Female Participants | 30.3 units per liter (U/L) | Standard Deviation 18 |
| Placebo Group | Serum Alanine Aminotransferase (ALT) in Female Participants | 22.2 units per liter (U/L) | Standard Deviation 12.4 |
Primary
Serum ALT in Males
Time frame: Day 5
Population: limited to males
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Serum ALT in Males | 31.1 units per liter (U/L) | Standard Deviation 29.7 |
| Placebo Group | Serum ALT in Males | 27.8 units per liter (U/L) | Standard Deviation 10.4 |
Primary
Serum Aspartate Aminotransferase (AST) in Females
Time frame: Day 5
Population: limited to females
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Serum Aspartate Aminotransferase (AST) in Females | 28.3 units per liter (U/L) | Standard Deviation 13 |
| Placebo Group | Serum Aspartate Aminotransferase (AST) in Females | 22.4 units per liter (U/L) | Standard Deviation 5.1 |
Primary
Serum AST in Males
Time frame: Day 5
Population: limited to males
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Serum AST in Males | 31 units per liter (U/L) | Standard Deviation 16.1 |
| Placebo Group | Serum AST in Males | 31 units per liter (U/L) | Standard Deviation 16.9 |
Primary
Serum Creatinine
Time frame: Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lactobacillus Reuteri Group | Serum Creatinine | 0.73 mg/dl | Standard Deviation 0.16 |
| Placebo Group | Serum Creatinine | 0.73 mg/dl | Standard Deviation 0.24 |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported | 18 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported | 5 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported | 67 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported | 32 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported | 13 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported | 19 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported | 41 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported | 15 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported | 1 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported | 12 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported | 15 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported | 2 days with symptom reported |
Secondary
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported
Time frame: Day 0 through 6 weeks after Day 0
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported | 4 days with symptom reported |
| Placebo Group | Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported | 3 days with symptom reported |
Secondary
Number of Subjects With at Least One PCR Positive Stool Specimen
Time frame: Average of 36 day follow up period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Reuteri Group | Number of Subjects With at Least One PCR Positive Stool Specimen | 9 participants |
| Placebo Group | Number of Subjects With at Least One PCR Positive Stool Specimen | 5 participants |