Early Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies (EMLFO-2)

Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are common devastating gastrointestinal diseases in premature infants. These infants often need surgical intervention to remove the dead bowel and create temporary enterostomies, resulting in short bowel syndrome (SBS), a malabsorption state due to insufficient bowel length or dysfunction to digest and absorb nutrients adequately.

These infants are often nourished primarily with parental nutrition (PN) which can lead to many complications including PN-associated liver disease. However, with enteral feeding, the remaining bowel can adapt somewhat to the shortened state, reducing the need for PN. Enteral fats appear to be the most trophic macronutrients with the long chain polyunsaturated fatty acids (LCPUFA) being the most beneficial in promoting bowel adaptation.

Fish oil (FO), a main source of n-3 LCPUFA, has been shown to promote bowel adaptation. Microlipid (ML) primarily contains n-6 PUFA and has been found to decrease ostomy output and increase weight gain in some SBS infants. WThe investigators will soon have completed a randomized clinical trial (EMLFO trial) (WFUHS IRB00011501, NCT01306838) entitled "Early Supplementation of Enteral Lipid with Combination of Microlipid and Fish Oil in Infants with Enterostomies". The preliminary data suggest that (a) by supplementing enteral ML/FO, we were able to decrease the use of IL; (b) premature infants in the treatment group who received ML/FO achieved higher enteral calorie (% of total calorie) intake before reanastomosis and better weight gain (g/day) after reanastomosis than those who received routine care in control group; and (c) the direct bilirubin level before reanastomosis tended to be lower in the treatment group than the control group although the difference was not statistically significant. Because the intervention consisted of both an increase in enteral fat intake as well as a specific type of fat intake (i.e. FO), it is unclear whether improved outcomes in the ML/FO group are attributable to FO's anti-inflammatory effects or the increased fat intake. Therefore, the investigators have designed a next randomized clinical trial to compare ML alone versus ML plus FO. We hypothesize that as compared to ML alone, ML plus FO will result in decreased systemic inflammation, as indicated by blood levels of inflammation-related proteins and indicators of oxidative stress.

Study Overview

• Status: Completed
• Conditions: Prematurity; Short Bowel Syndrome (SBS); Necrotizing Enterocolitis (NEC); Intestine Perforation
• Intervention / Treatment: Dietary supplement: Microlipid with fish oil; Dietary supplement: Microlipid

Detailed Description

In comparison to EMLFO trial, the EMLFO-2 study will modify the eligibility criteria to only enroll the infants who have birthweight equal to or less than 1250 g with a jejunostomy or ileostomy as the result of surgical treatment for small intestine perforation or NEC in order to increase the homogeneity of patient population.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 months (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. infants (age range: newborn to ≤ 2-month-old) whose birth weight are ≤ 1250g;
2. who are admitted to BCH NICU for surgical intervention for NEC or small intestine perforation and then to have a jejunostomy or ileostomy;
3. who are expected to need full or partial PN for at least 21days from the day of ostomy placement; and
4. who have received enteral feedings ≤ 4 days since ostomy placement.

Exclusion Criteria:

1. infant with birth weight > 1250g;
2. infant with colostomy;

3. infants with enterostomy but

   • unable to obtain written informed consent from parent;
   • presence of congenital liver, renal, or metabolic diseases or syndromes or perinatal asphyxia;
   • ostomy caused by surgical treatment for a condition other than NEC or small intestine perforation; and
   • unable to initiate enteral feeding for more than 28 days since ostomy placement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Microlipid with fish oil group; This group will be given early enteral lipid supplementation with Microlipid and fish oil.	Dietary supplement: Microlipid with fish oil; Fish oil will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which both will be continued until reanastomosis.
ACTIVE_COMPARATOR: Microlipid group; This group will be given early enteral lipid supplementation only with Microlipid.	Dietary supplement: Microlipid; A small amount (ml) of Microlipid to match the amount of fish oil in ML/FO group will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which will be continued until reanastomosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Serum Biomarkers of Inflammatory Cytokines	Compare the serum biomarkers of inflammatory cytokines of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis	2 years and 5 months
The Serum Biomarkers of Oxidative Stress	Compare the serum biomarkers of oxidative stress of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis	2 years and 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Average Enteral Calorie (Total Calorie) Intake Before Reanast	To compare the average enteral calorie (total calorie) intake of infants receiving ML/FO to the group only receiving ML between the initial feeding after placement of an ostomy and reanastomosis	2 years and 5 months
The Average Weight Gain (g/Day) After Reanastomosis	To compare the the average weight gain (g/day) of infants receiving ML/FO to the infants only receiving ML after reanastomosis	2 years and 5 months

Collaborators and Investigators

• Sponsor: Wake Forest University
• Investigators: Principal Investigator: Qing Yang, MD, PhD, WFUHS

Publications and helpful links

General Publications

• Yang Q, Kock ND. Effects of dietary fish oil on intestinal adaptation in 20-day-old weanling rats after massive ileocecal resection. Pediatr Res. 2010 Sep;68(3):183-7. doi: 10.1203/PDR.0b013e3181eb2ee5.
• Yang Q, Lan T, Chen Y, Dawson PA. Dietary fish oil increases fat absorption and fecal bile acid content without altering bile acid synthesis in 20-d-old weanling rats following massive ileocecal resection. Pediatr Res. 2012 Jul;72(1):38-42. doi: 10.1038/pr.2012.41. Epub 2012 Mar 23.
• Yang Q, Welch CD, Ayers K, Turner C, Pranikoff T. Early enteral fat supplementation with microlipid(R) and fish oil in the treatment of two premature infants with short bowel. Neonatology. 2010;98(4):348-53. doi: 10.1159/000316067. Epub 2010 Oct 27.
• Woods CW, Ayers K, Turner C, Pranikoff T and Qing Yang. A Novel Nutritional Approach to Prevent Parenteral Nutrition-Associated Cholestasis in Two Premature Infants with Short Bowel Syndrome. ICAN: Infant, Child, & Adolescent Nutrition 2013 5: 32-36.
• Yang Q, Ayers K, Chen Y, Helderman J, Welch CD, O'Shea TM. Early enteral fat supplement and fish oil increases fat absorption in the premature infant with an enterostomy. J Pediatr. 2013 Aug;163(2):429-34. doi: 10.1016/j.jpeds.2013.01.056. Epub 2013 Feb 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2012
• Primary Completion (ACTUAL): March 17, 2015
• Study Completion (ACTUAL): March 17, 2015

Study Registration Dates

• First Submitted: August 18, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (ESTIMATE): August 28, 2012

Study Record Updates

• Last Update Posted (ACTUAL): December 4, 2018
• Last Update Submitted That Met QC Criteria: November 7, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: NEC, SBS, enterostomy, fish oil, Microlipid, Intralipid,; enteral fat
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Malabsorption Syndromes; Enterocolitis; Enterocolitis, Necrotizing; Intestinal Perforation; Short Bowel Syndrome
• Other Study ID Numbers: IRB00021481

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No