Lactobacillus Reuteri Strain Combination in Children Treated With PPI

Aim of study

Our aims are to assess if Gastrus administration:

• reduces the incidence of SIBO;
• reduces the risk of infections in children treated with gastric-acid inhibitors;
• prevents perturbation of gut microbiota and related dysbiosis;

Study Product Gastrus sachets/chewable caps: 2x108 CFU Lactobacillus reuteri DSM 17938 + 2x108 CFU Lactobacillus reuteri ATCC PTA 6475.

Placebo sachets/chewable caps: Identical in shape, colour and taste to Gastrus capsules but without the Lactobacillus reuteri components.

Both study products are delivered in identical containers. Dosing: Two sachets/cps twice a day. Length of treatment: Gastrus or placebo will be administered for all the duration of PPI administration (8 weeks) plus two weeks after its discontinuation. A final evaluation will be performed 4 weeks after the discontinuation of both Gastrus and placebo.

Compliance, PP and ITT To be considered compliant the participant should have consumed at leas 80% of the doses. In order to improve compliance, the participants will be equipped with alarm-devices. Compliant patients will be assessed as Per-Protocol (PP). Patients that are non-compliant will be included in the Intention-To-Treat analysis.

Outcomes Primary efficacy parameter This study aimed at investigating if Gastrus administration prevents the emergence of SIBO and reduces the risk of infections in children treated with proton pump inhibitors and.

Exploratory parameters Ability of Gastrus to prevent and control gut microbiota alteration; Ability of Gastrus to improve GI symptoms for which the drug has been prescribed.

Sample size calculation Assuming that the average rate of infection in patient who assume PPI is 32% as compared to 9% of those who do not use the drug (16), to demonstrate an efficacy of the probiotic, keeping a power of the study of 80% and a p of 0,05 we need 78 patients for group that, considering a drop out of 10%, will became 86 per group (patient younger/older 4 years of age:0,75) This sample size is by far larger than needed to demonstrate the preventive effect on SIBO emergence.

Inclusion criteria

• Age: children between 1 month and 14 years of age;

o We start with children older than 4 years of age.

• Necessity of therapy with Proton Pump Inhibitors for Gastroesophageal reflux disease and/or Functional Dyspepsia;
• Informed consent obtained.

Exclusion criteria

• Neurological pathologies (PCI and Spastic tetra-paresis);
• Nasogastric feeding;
• Known immunodeficiency;
• Previous therapy with gastric acid inhibitors;
• HP infection;
• Assumption of prebiotics, other probiotics or symbiotics in the previous month;
• Malnutrition or severe dystrophy;
• Cystic Fibrosis.