Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis

Heat Killed Probiotics in the Prevention of Necrotizing Enterocolitis (NEC) in Premature Neonates

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.

Study Overview

• Status: Unknown
• Conditions: Necrotizing Enterocolitis; Enterocolitis, Necrotizing
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Heat Inactivated probiotics

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 Type: Interventional
• Enrollment (Anticipated): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alona Bin-Nun, MD; Phone Number: 0508685757; Email: alona.binnun@gmail.com

Study Locations

• Israel
  • Jerusalem, Israel, 91031
    • Neonatal Intensive Care Unit - Shaare Zedek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 hours to 1 week (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control Group; Dietary Supplement: Placebo 2 cc/day of placebo diluted in mother's milk (when available) or premature formula.	Dietary supplement: Placebo; 2 cc of milk will be given to control group
ACTIVE_COMPARATOR: Treatment Group; 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.	Dietary supplement: Heat Inactivated probiotics; Biotikid, a probiotic mixture, will be heated to 100 degrees Centigrade for 10 minutes to inactivate and then 1 tsp will be diluted in milk and give with feeds to treatment group

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Shaare Zedek Medical Center

Publications and helpful links

General Publications

• Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci. 2010 Mar 15;13(6):253-62. doi: 10.3923/pjbs.2010.253.262.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: May 22, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (ESTIMATE): June 13, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): June 16, 2016
• Last Update Submitted That Met QC Criteria: June 15, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: SZMC 0297-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO