Clinical trial NCT01674478: Early Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies
Official title: Early Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prematurity
Intestine Perforation
Necrotizing Enterocolitis (NEC)
Short Bowel Syndrome (SBS)
Keywords: NEC, SBS, enterostomy, fish oil, Microlipid, Intralipid,
enteral fat
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2012-08-28
Enrollment: 18
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Serum Biomarkers of Inflammatory Cytokines
timeFrame: 2 years and 5 months
measure: The Serum Biomarkers of Oxidative Stress
timeFrame: 2 years and 5 months
Secondary outcomes:
measure: The Average Enteral Calorie (Total Calorie) Intake Before Reanast
timeFrame: 2 years and 5 months
measure: The Average Weight Gain (g/Day) After Reanastomosis
timeFrame: 2 years and 5 months
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Science
state: North Carolina
Study officials:
affiliation: WFUHS
name: Qing Yang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.