Safety of Lactobacillus Reuteri in Healthy Children Aged 2-24 Months
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase I double blinded randomized trial of the safety and tolerability of Lactobacillus
      reuteri DSM 17938 given for five successive days in healthy children. Sixty children will
      receive study product at a treatment to placebo ratio of 2:1 and followed for 3 months for
      safety outcomes.
    

Detailed description: 
      The study is a single center Phase 1 double blind placebo controlled trial of Lactobacillus
      reuteri DSM 17938 in children aged 2-24 months. The study population is based in a community
      with a registered clinical trial center in rural Peru where this protocol can be done in a
      highly controlled setting. The study is intended to enroll healthy children living in a
      resource constrained setting where chronic undernutrition and diarrheal disease is common, as
      this is the population that is most likely to receive benefit from the use of this and or
      other probiotic products for the treatment of acute infectious diarrhea and environmental
      enteropathy.

      Up to 100 subjects will be enrolled in order to obtain the randomization of 60 subjects, who
      will receive study product or placebo at a ratio of 2:1. Participants will be enrolled
      between the ages of 8 weeks and 24 months. There will be no age stratification. Participants
      will be screened with a baseline history and physical examination and laboratory tests to
      determine the HIV status of the child, as well baseline laboratory tests to evaluate occult
      infections, hepatic function, and renal function. Upon randomization subjects will be
      screened and randomized to a treatment arm. Product will be administered under the direct
      supervision of study staff daily for 5 days. The primary outcome is the safety and
      tolerability of the product at this dose and formulation. Safety will be assessed by the
      monitoring of baseline laboratory tests at 5 and 28 days following the initiation of therapy
      and by AE monitoring. Tolerability will be evaluated by analyzing 28 day diary cards that are
      distributed to all randomized subjects on which parents record their child's symptoms
      (specifically fever, anorexia/oral intake, vomiting, diarrhea, irritability, rash, wheezing,
      or open fields which allows them to describe any issue their child may experience and grade
      its severity) . Secondary outcomes include:

      1) The assessment of the duration of shedding of Lactobacillus reuteri (Lr) strain DSM 17938
      following administration. This will be determined by and endpoint PCR assay for L. reuteri
      done on stool collected on D3, D5, D12, D15, D18, D24, D28, D36 on all participants.

      The planned enrollment period is four months and the participation of individual subjects is
      for 3 months. The study should be completed in 7 months. Safety monitoring by treatment
      group, i.e., infants assigned to active or placebo study product will be conducted by NIDDK
      appointed DSMB under the direction of the NIDDK Program Official.
    

Intervention name(s): Lactobacillus reuteri 17938; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): probiotic; Composition Sunflower oil, medium chain triglyceride oil and silicon dioxide. Total viable count of L. reuteri is zero CFU/ 5 drops.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Safety