Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis

Phase 2

• Conditions: Enterocolitis, Necrotizing; Necrotizing Enterocolitis
• Interventions: Dietary Supplement: Heat Inactivated probiotics; Dietary Supplement: Placebo

• Registration Number: NCT02796703
• Lead Sponsor: Shaare Zedek Medical Center

Brief Summary

Prophylactic probiotics have been shown to decrease the incidence of Necrotizing Enterocolitis (NEC) in premature neonates. However, there is some resistance to giving live bacteria to small babies. Based on animal data, the investigators hypothesized that heat inactivated probiotics would also reduce NEC.

Detailed Description

Preterm neonates, \<1500 gm birth weight will potentially be candidates for study and will be recruited when they begin enteral feeding. The infants will be prospectively and randomly assigned to one of two groups:

1. Treatment group - to receive daily inactivated probiotic prophylaxis starting with the initiation of feeds. 1 tsp powder will be diluted in 2 cc of mother's milk when possible or in Similac Special Care formula 24 cal when mother's milk is not available; and

2. Control group - to receive 2 cc/day of placebo similarly diluted. Supplements will be continued until the infant tolerates enteral feeds of 100 cc/kg/day or reaches 35 weeks post conceptual age (whichever comes LAST). Biotikid, a probiotic mixture, will be heated to 100 degrees C for 10 minutes. Babies will be followed clinically for signs of NEC, and with urine intestinal fatty acid binding protein (IFABP) and fecal calprotectin levels.

The investigators primary aim is to demonstrate that premature neonates who are treated prophylactically with heat inactivated probiotics will have less necrotizing enterocolitis when compared to age matched infants given placebo.

The investigators secondary objectives are to demonstrate the following:

* That the decrease in NEC will coincide with improved intestinal barrier integrity, as reflected by levels of:

* I-FABP in urine

* Fecal Calprotectin

Study Timeline

• Study First Submitted: 2016-05-22
• Status Verified: 2016-06
• Study Start: 2016-06
• Study First Submitted QC: 2016-06-10
• Study First Posted: 2016-06-13
• Last Update Submitted: 2016-06-15
• Last Update Posted: 2016-06-16
• Primary Completion: 2020-07
• Study Completion: 2020-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• Preterm neonates
• ≤1500 gm birth weight

Exclusion Criteria

• Infants who are not deemed likely to survive more than one week;
• Infants who are not started on enteral feeds by one week of age;
• Infants who have significant congenital malformations or other gastrointestinal problem

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Heat Inactivated probiotics	Dietary Supplement: Heat Inactivated Probiotics 1 tsp heat inactivated Biotikid powder will be diluted in 2 cc of mother's milk (when available) or premature formula.
Control Group	Placebo	Dietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula.

Primary Outcome Measures

Name	Time	Method
Necrotizing Enterocolitis, Bell Stage 2 or above, or Death	Birth until 40 weeks post-conceptional age	Necrotizing Enterocolitis diagnosis will be based on clinical and radiographic criteria

Secondary Outcome Measures

Name	Time	Method
Increased Urine IFABP Levels	Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age
Increased Fecal Calprotectin Levels	Weekly, from date of randomization until full enteral feeds (100 cc/kg/day) achieved or until death or necrotizing enterocolitis is diagnosed, whichever comes first until 37 weeks postconceptional age

Trial Locations

Locations (1)

Neonatal Intensive Care Unit - Shaare Zedek Medical Center; 🇮🇱 Jerusalem, Israel