CClinicalTrials.gg
Sign In
CompletedNCT00774163Updated Dec 19, 2016Results posted

Safety of Lactobacillus Reuteri in Healthy Volunteers

A Phase 1 interventional study of Lactobacillus reuteri and Placebo in Healthy, sponsored by Tulane University School of Medicine. Completed at 1 site in Peru. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-12-19.

Sponsored by Tulane University School of Medicine · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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).

02

Conditions studied

  • Healthy

Keywords

  • probiotics
  • lactobacillus
  • reuteri
  • none (safety only)
03

In context

Lead sponsor

Tulane University School of Medicine is the lead sponsor of 20 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts 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).

Exclusion criteria

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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    1

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

    Biological: Lactobacillus reuteri

  • Placebo comparator
    2

    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

Interventions

  • BiologicalLactobacillus reuteri

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

    Also known as: BioGaia Probiotic Drops

  • OtherPlacebo

    5 drops of the oil vehicle used in manufacturing the Lr suspension, given once daily for a five-day study period

06

What researchers measure

Primary outcomes

  1. 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

  2. Mean Daily Temperature

    Measured daily during 5 days of study product administration

    Time frame: 5 days of study product administration

  3. Leukocyte Count on Day 5

    Time frame: Measured on day 5

  4. Serum Alanine Aminotransferase (ALT) in Female Participants

    Time frame: Day 5

  5. Serum ALT in Males

    Time frame: Day 5

  6. Serum Aspartate Aminotransferase (AST) in Females

    Time frame: Day 5

  7. Serum AST in Males

    Time frame: Day 5

  8. Blood Urea Nitrogen

    Time frame: Day 5

  9. Serum Creatinine

    Time frame: Day 5

Secondary outcomes

  1. Number of Subjects With at Least One PCR Positive Stool Specimen

    Time frame: Average of 36 day follow up period

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

07

Results

Posted Jul 12, 2013

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 flow — Overall Study
MilestoneLactobacillus GroupPlacebo Group
Started3015
Completed3015
Not completed00

Outcome measures

PrimaryNumber 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
Reported as:
Number · participants
Number of Participants With a Positive Blood Culture for L. Reuteri
participantsLactobacillus Reuteri GroupPlacebo Group
Number of Participants With a Positive Blood Culture for L. Reuteri00
SecondaryNumber of Subjects With at Least One PCR Positive Stool Specimen
Time frame:
Average of 36 day follow up period
Reported as:
Number · participants
Number of Subjects With at Least One PCR Positive Stool Specimen
participantsLactobacillus Reuteri GroupPlacebo Group
Number of Subjects With at Least One PCR Positive Stool Specimen95
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Vomiting Reported43
PrimaryMean Daily Temperature

Measured daily during 5 days of study product administration

Time frame:
5 days of study product administration
Reported as:
Mean · Degrees Celcius
Mean Daily Temperature
Degrees CelciusLactobacillus Reuteri GroupPlacebo Group
Mean Daily Temperature36.02 ± 0.536.04 ± 0.5
PrimaryLeukocyte Count on Day 5
Time frame:
Measured on day 5
Reported as:
Mean · cells per cubic millimeter
Leukocyte Count on Day 5
cells per cubic millimeterLactobacillus Reuteri GroupPlacebo Group
Leukocyte Count on Day 56936 ± 13317893 ± 1168
PrimarySerum Alanine Aminotransferase (ALT) in Female Participants
Time frame:
Day 5
Reported as:
Mean · units per liter (U/L)
Serum Alanine Aminotransferase (ALT) in Female Participants
units per liter (U/L)Lactobacillus Reuteri GroupPlacebo Group
Serum Alanine Aminotransferase (ALT) in Female Participants30.3 ± 18.022.2 ± 12.4
PrimarySerum ALT in Males
Time frame:
Day 5
Reported as:
Mean · units per liter (U/L)
Serum ALT in Males
units per liter (U/L)Lactobacillus Reuteri GroupPlacebo Group
Serum ALT in Males31.1 ± 29.727.8 ± 10.4
PrimarySerum Aspartate Aminotransferase (AST) in Females
Time frame:
Day 5
Reported as:
Mean · units per liter (U/L)
Serum Aspartate Aminotransferase (AST) in Females
units per liter (U/L)Lactobacillus Reuteri GroupPlacebo Group
Serum Aspartate Aminotransferase (AST) in Females28.3 ± 1322.4 ± 5.1
PrimarySerum AST in Males
Time frame:
Day 5
Reported as:
Mean · units per liter (U/L)
Serum AST in Males
units per liter (U/L)Lactobacillus Reuteri GroupPlacebo Group
Serum AST in Males31 ± 16.131 ± 16.9
PrimaryBlood Urea Nitrogen
Time frame:
Day 5
Reported as:
Mean · mg/dl
Blood Urea Nitrogen
mg/dlLactobacillus Reuteri GroupPlacebo Group
Blood Urea Nitrogen22.4 ± 7.019.3 ± 5.4
PrimarySerum Creatinine
Time frame:
Day 5
Reported as:
Mean · mg/dl
Serum Creatinine
mg/dlLactobacillus Reuteri GroupPlacebo Group
Serum Creatinine0.73 ± 0.160.73 ± 0.24
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Pruritis Reported112
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Headache Reported6732
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Malaise Reported1319
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Diarrhea Reported185
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Myalgia Reported4115
SecondaryClinical 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
Reported as:
Number · days with symptom reported
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported
days with symptom reportedLactobacillus Reuteri GroupPlacebo Group
Clinical Tolerance of Lactobacillus Reuteri (Lr) Strain DSM 17938 Based on Number of Days With Subjective Fever Reported152

Adverse events

Collected over 6 months from initiation of study. Non-serious events are listed at a 1% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lactobacillus Reuteri Group—0/30 (0%)27/30 (90%)
Placebo Group—0/15 (0%)13/15 (86.7%)
Most frequent other events
Showing 10 of 15
Most frequent other events
EventLactobacillus Reuteri GroupPlacebo Group
HeadacheNervous system disorders20/309/15
Lumbar painMusculoskeletal and connective tissue disorders15/305/15
RhinorrheaRespiratory, thoracic and mediastinal disorders13/305/15
Abdominal painGastrointestinal disorders8/306/15
MyalgiaMusculoskeletal and connective tissue disorders8/305/15
sore throatRespiratory, thoracic and mediastinal disorders8/305/15
DiarrheaGastrointestinal disorders9/304/15
Nausea and vomitingGastrointestinal disorders5/304/15
PruritisSkin and subcutaneous tissue disorders2/303/15
dysuriaRenal and urinary disorders6/303/15

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Lactobacillus GroupPlacebo GroupTotal
<=18 years000
Between 18 and 65 years301545
>=65 years000
Age, Continuous
Age, Continuous(years)Lactobacillus GroupPlacebo GroupTotal
Mean39.1 ± 2.032.3 ± 2.336.8 ± 1.8
Gender
Gender(Participants)Lactobacillus GroupPlacebo GroupTotal
Female23932
Male7613
Region of Enrollment
Region of Enrollment(participants)Lactobacillus GroupPlacebo GroupTotal
Peru301545
08

Study locations

1 site
  • Community of Santa Clara
    Iquitos, Loreto, Peru
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 19, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00774163
Lead sponsor
Tulane University School of Medicine
Collaborators
National Center for Complementary and Integrative Health (NCCIH), Johns Hopkins Bloomberg School of Public Health, Asociacion Benefica Prisma
Responsible party
Richard A. Oberhelman (Professor, Tulane University School of Medicine) — Principal investigator
First posted
Oct 17, 2008
Start date
Feb 2010
Primary completion
Jun 2010
Completion
Oct 2010
Results posted
Jul 12, 2013
Last update
Dec 19, 2016

Study contacts

Richard A Oberhelman, MD
principal investigator · Tulane School of Public Health and Tropical Medicine
Margaret N Kosek, MD
study director · Johns Hopkins Bloomberg School of Public Health

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Tulane University School of Medicine

Start the discussion