Safety of Lactobacillus Reuteri in Healthy Children Ages 2 to 5 Years in Peru

NCT ID: NCT02124122

Last Updated: 2017-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-01-31

Brief Summary

This is a Phase 1 study to assess the safety and tolerability of Lactobacillus reuteri (Lr) strain DSM 17938 in healthy children in Peru. It is a preliminary study in support of a clinical trial to assess safety and efficacy of L. reuteri 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).

In the first 30 subjects randomized, administration of each dose of the study preparation drops (A or B above) will be immediately followed by offering 2 ounces of flavored PediaSure ® (Abbott Laboratories) nutritional supplement to each child. The second 30 subjects enrolled will not be offered PediaSure ® after product administration. This format will also allow us to assess the impact of concurrent administration of a buffering non-lactose containing formula with prebiotic nutritional properties on intestinal colonization with L. reuteri by PCR.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lactobacillus

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).

Group Type: EXPERIMENTAL

Lactobacillus reuteri

Intervention Type: BIOLOGICAL

Probiotic

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 (BioGaia AB, Stockholm, Sweden).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo

Interventions

Lactobacillus reuteri

Probiotic

Intervention Type: BIOLOGICAL

Placebo

Placebo

Intervention Type: BIOLOGICAL

Other Intervention Names

BioGaia Probiotic Drops

Eligibility Criteria

Exclusion Criteria

• 1) No enrollment of family members in households where any of the following are present:

1. Another study participant in the household

2. Pregnancy or current breastfeeding by any household member

3. Presence of an infant under age 6 months living in the household

4. Presence of immune suppressed individuals or use of immunosuppressive agents (including but not limited to corticosteroids and methotrexate, etc.) by any household member

5. Presence of a serious congenital anomaly or chronic medical condition that in the opinion of the investigators would contraindicate participation in any household member, including history of gastrointestinal surgery, chronic gastrointestinal illness, abnormal intestinal anatomy, or abnormal bowel functionality

2) Allergy to penicillin or cephalosporins or gentamicin 3) History of antibiotic use in the last 30 days 4) Use of probiotic products within the past 90 days, including masato (local product with fermenting bacteria) and yogurt products containing live bacterial cultures.

5) History of diarrheal illness within the past 30 days 6) Presence of fever or a pre-existing adverse event monitored in the study 7) Positive results on serum diagnostic tests for antibodies to HIV.

Testing for Hepatitis B core antigen, and Hepatitis C is not necessary in children as in adults, since there is universal vaccination for Hepatitis B among children in this community, and both forms of hepatitis are rare and largely asymptomatic in this age group.

8) Presence of severe anemia, defined as serum hemoglobin < 8 gm/dL

9) Out of range laboratory values for tests monitored as potential adverse events, as described in Appendix 2, B. LABORATORY VALUES, and detected based on Day 0 blood test results. However, subjects will only be excluded based on serum hemoglobin if they meet exclusion criterion 8.

10) Pre-enrollment stool sample (collected within 14 days of Day 1 of the study) is positive for L. reuteri by PCR.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

Johns Hopkins Bloomberg School of Public Health

OTHER

Sponsor Role: collaborator

Asociacion Benefica Prisma

OTHER

Sponsor Role: collaborator

Tulane University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Richard A. Oberhelman

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard A Oberhelman, MD

Role: PRINCIPAL_INVESTIGATOR

Tulane School of Public Health and Tropical Medicine

Margaret N Kosek, MD

Role: STUDY_DIRECTOR

Johns Hopkins Bloomberg School of Public Health

Locations

Community of Santa Clara

Santa Clara, Loreto, Peru

Countries

Peru

References

Kosek MN, Penataro-Yori P, Paredes-Olortegui M, Lefante J, Ramal-Asayag C, Zamora-Babilonia M, Meza-Sanchez G, Oberhelman RA. Safety of Lactobacillus Reuteri DSM 17938 in Healthy Children 2-5 Years of Age. Pediatr Infect Dis J. 2019 Aug;38(8):e178-e180. doi: 10.1097/INF.0000000000002267.

Reference Type: DERIVED

PMID: 30531312 (View on PubMed)

Other Identifiers

5U01AT002733

Identifier Type: NIH

Identifier Source: secondary_id

View Link

FDA IND# 13710-Protocol 2

Identifier Type: -

Identifier Source: org_study_id