The Effects of Lactobacillus Reuteri DSM 17938 on Immunomodulation and Gastric Motility in Preterm Newborns

University of Bari

Status and phase: Completed; Early Phase 1

Conditions: Preterm Birth

Treatments: Dietary Supplement: Lactobacillus Reuteri; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00985816

FI-LR2009

Details and patient eligibility

About

The investigators propose a Phase II interventional trial to investigate the role of Lactobacillus reuteri DSM 17938 on the intestinal motility and immune response of premature infants and further evaluate safety of the use of this probiotic in a population of premature infants.

Full description

Hypothesis Administration of Lactobacillus reuteri to premature infants will improve their intestinal motility when compared with infants receiving placebo. Primary Objective Evaluate the effects of L. reuteri in the intestinal motility by measuring the gastric emptying rate in infants before and after 21 consecutive days of administration of L. reuteri.

Secondary Objectives 1. Mechanisms of action of L. reuteri - L.reuteri impact in the host immune response by determining fecal cytokines, sIgA and calprotectin before and after 21 days of administration - L.reuteri rate of colonization after its administration.

2. Efficacy and safety of L. reuteri to premature infants - Clinical beneficial effects secondary to the administration of L. reuteri to premature infants. The following clinical outcomes will be identified and compared between groups:

• Number of gastrointestinal symptoms (regurgitation, vomiting, stasis)
• Days to full feeds. Number of days to reach full feeds defined as > 120cc/kg/day) x2 days or more.
• Days on parenteral nutrition
• Weight gain defined as the number of days needed to reach 150% of birth weight
• Length of hospital stay
• Any possible side effects and adverse events secondary to the administration of L. reuteri to premature infants.
• Incidence of late onset sepsis.
• Incidence and severity of necrotizing enterocolitis categorized by Bell's classification
• Use of antibiotics (number of days on antibiotics during the hospital stay)
• Mortality (at 28 days after birth and at hospital discharge).

Enrollment: 80 estimated patients

Sex: All

Ages: 3 days to 1 month old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Gestational age 30 - 32 weeks. Gestational age will be defined by the best estimate based on prenatal ultrasound in the first trimester, DLM and/or Balard Score after birth.

Exclusion criteria

• Cardiovascular or (respiratory) instability after 48 hours of age - Chromosomal anomalies.
• Major congenital anomalies (complex cardiac anomalies, congenital hydrocephalus, renal dysplasia)
• Congenital (e.g. jejunal atresia) and acquired (e.g. GI perforation) gastrointestinal pathology precluding oral feed and/or requiring major surgical or medical intervention
• Parental refusal
• Prior enrollment into a conflicting clinical trial. Conflicting clinical trial will be those in which the intervention could modify the outcome of the present study, for example studies that could alter the intestinal motility or the immune response of the premature infants.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

L reuteri DSM 17938

Active Comparator group

Description:

L. reuteri DSM 17938 will be given at a dose of 1x108 colony forming units (CFU)/day in an oil formulation delivered from a drop bottle. In the active study product, freeze-dried L. reuteri is suspended in a mixture of pharmaceutical grade medium chain triglycerides and sunflower oil together with pharmaceutical grade silicon dioxide to give the product the correct rheological properties (Connolly, 2005). The placebo consists of an identical formulation except that the L. reuteri is not present. This dose of the oil formulation with L. reuteri has been shown to induce significant colonisation in infants and is well-tolerated (Abrahamsson et al., 2007; Savino et al., 2007; Indrio et al., 2008).

Treatment:

Dietary Supplement: Lactobacillus Reuteri

Placebo

Placebo Comparator group

Treatment:

Dietary Supplement: Placebo