Trial Outcomes & Findings for Safety of Lactobacillus Reuteri in Healthy Volunteers (NCT NCT00774163)

NCT ID: NCT00774163

Last Updated: 2016-12-19

Results Overview

To assess association between administration of Lactobacillus reuteri (Lr) strain DSM 17938 and abnormal lab values (CBC, BUN, Creatinine, AST, ALT, blood culture).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 45 participants
• Primary outcome timeframe: participants were followed for an average of 36 days
• Results posted on: 2016-12-19

Participant Flow

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.

Participant milestones

Measure	Lactobacillus Group Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	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
Overall Study STARTED	30	15
Overall Study COMPLETED	30	15
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety of Lactobacillus Reuteri in Healthy Volunteers

Baseline characteristics by cohort

Measure	Lactobacillus Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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	Total n=45 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants	15 Participants n=7 Participants	45 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	39.1 years STANDARD_DEVIATION 2.0 • n=5 Participants	32.3 years STANDARD_DEVIATION 2.3 • n=7 Participants	36.8 years STANDARD_DEVIATION 1.8 • n=5 Participants
Gender Female	23 Participants n=5 Participants	9 Participants n=7 Participants	32 Participants n=5 Participants
Gender Male	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment Peru	30 participants n=5 Participants	15 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: participants were followed for an average of 36 days

Population: 2:1 randomization Lactbacillus:placebo using a randomizatin table as specified in the protocol

To assess association between administration of Lactobacillus reuteri (Lr) strain DSM 17938 and abnormal lab values (CBC, BUN, Creatinine, AST, ALT, blood culture).

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Number of Participants With a Positive Blood Culture for L. Reuteri	0 participants	0 participants

PRIMARY outcome

Timeframe: 5 days of study product administration

Measured daily during 5 days of study product administration

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Mean Daily Temperature	36.02 Degrees Celcius Standard Deviation 0.5	36.04 Degrees Celcius Standard Deviation 0.5

PRIMARY outcome

Timeframe: Measured on day 5

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Leukocyte Count on Day 5	6936 cells per cubic millimeter Standard Deviation 1331	7893 cells per cubic millimeter Standard Deviation 1168

PRIMARY outcome

Timeframe: Day 5

Population: limited to females

Outcome measures

Measure	Lactobacillus Reuteri Group n=23 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=9 Participants 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
Serum Alanine Aminotransferase (ALT) in Female Participants	30.3 units per liter (U/L) Standard Deviation 18.0	22.2 units per liter (U/L) Standard Deviation 12.4

PRIMARY outcome

Timeframe: Day 5

Population: limited to males

Outcome measures

Measure	Lactobacillus Reuteri Group n=7 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=6 Participants 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
Serum ALT in Males	31.1 units per liter (U/L) Standard Deviation 29.7	27.8 units per liter (U/L) Standard Deviation 10.4

PRIMARY outcome

Timeframe: Day 5

Population: limited to females

Outcome measures

Measure	Lactobacillus Reuteri Group n=23 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=9 Participants 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
Serum Aspartate Aminotransferase (AST) in Females	28.3 units per liter (U/L) Standard Deviation 13	22.4 units per liter (U/L) Standard Deviation 5.1

PRIMARY outcome

Timeframe: Day 5

Population: limited to males

Outcome measures

Measure	Lactobacillus Reuteri Group n=7 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=6 Participants 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
Serum AST in Males	31 units per liter (U/L) Standard Deviation 16.1	31 units per liter (U/L) Standard Deviation 16.9

PRIMARY outcome

Timeframe: Day 5

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Blood Urea Nitrogen	22.4 mg/dl Standard Deviation 7.0	19.3 mg/dl Standard Deviation 5.4

PRIMARY outcome

Timeframe: Day 5

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Serum Creatinine	0.73 mg/dl Standard Deviation 0.16	0.73 mg/dl Standard Deviation 0.24

SECONDARY outcome

Timeframe: Average of 36 day follow up period

Outcome measures

Measure	Lactobacillus Reuteri Group n=30 Participants Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 Participants 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
Number of Subjects With at Least One PCR Positive Stool Specimen	9 participants	5 participants

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 Days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 Days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported	4 days with symptom reported	3 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported	1 days with symptom reported	12 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported	67 days with symptom reported	32 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported	13 days with symptom reported	19 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported	18 days with symptom reported	5 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported	41 days with symptom reported	15 days with symptom reported

SECONDARY outcome

Timeframe: Day 0 through 6 weeks after Day 0

Outcome measures

Measure	Lactobacillus Reuteri Group n=1230 days of observation Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=615 days of observation 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
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported	15 days with symptom reported	2 days with symptom reported

Adverse Events

Lactobacillus Reuteri Group

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Lactobacillus Reuteri Group n=30 participants at risk Lactobacillus reuteri (Lr): 108 (100 million) organisms of Lactobacillus reuteri per dose, given once daily for a five-day treatment period	Placebo Group n=15 participants at risk 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
Gastrointestinal disorders Nausea and vomiting	16.7% 5/30 • Number of events 8 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	26.7% 4/15 • Number of events 7 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Gastrointestinal disorders Diarrhea	30.0% 9/30 • Number of events 10 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	26.7% 4/15 • Number of events 4 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Nervous system disorders Headache	66.7% 20/30 • Number of events 38 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	60.0% 9/15 • Number of events 23 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Musculoskeletal and connective tissue disorders Myalgia	26.7% 8/30 • Number of events 13 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	33.3% 5/15 • Number of events 8 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Skin and subcutaneous tissue disorders Rash	13.3% 4/30 • Number of events 6 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	6.7% 1/15 • Number of events 1 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Skin and subcutaneous tissue disorders Pruritis	6.7% 2/30 • Number of events 3 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	20.0% 3/15 • Number of events 7 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Infections and infestations Fever	16.7% 5/30 • Number of events 6 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	13.3% 2/15 • Number of events 2 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Gastrointestinal disorders Abdominal pain	26.7% 8/30 • Number of events 13 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	40.0% 6/15 • Number of events 10 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	43.3% 13/30 • Number of events 17 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	33.3% 5/15 • Number of events 7 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Reproductive system and breast disorders vaginal discharge	6.7% 2/30 • Number of events 2 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	0.00% 0/15 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Renal and urinary disorders dysuria	20.0% 6/30 • Number of events 17 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	20.0% 3/15 • Number of events 7 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Injury, poisoning and procedural complications laceration	6.7% 2/30 • Number of events 2 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	6.7% 1/15 • Number of events 1 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Musculoskeletal and connective tissue disorders Lumbar pain	50.0% 15/30 • Number of events 22 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	33.3% 5/15 • Number of events 9 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Respiratory, thoracic and mediastinal disorders cough	13.3% 4/30 • Number of events 6 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	20.0% 3/15 • Number of events 4 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.
Respiratory, thoracic and mediastinal disorders sore throat	26.7% 8/30 • Number of events 10 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.	33.3% 5/15 • Number of events 6 • 6 months from initiation of study AEs are scored as grade 1= mild, grade 1= moderate, grade 3 = severe, and grade 4 = life threatening based on the subject's interpretation of their symptom severity.

Additional Information

Dr. Richard Oberhelman

Tulane University School of Public Health and Tropical Medicine

Phone: 504-988-2511

Email: oberhel@tulane.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place