Clinical trial NCT01306838: Early Provision of Enteral Microlipid and Fish Oil to Infants With Enterostomy
Official title: Early Supplementation of Enteral Lipid With Combination of Microlipid and Fish Oil in Infants With Enterostomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Short Bowel Syndrome
Necrotizing Enterocolitis
Small Intestine Perforation
Keywords: Short bowel syndrome
Necrotizing enterocolitis
Small intestine perforation
Enterostomy
Intralipid
Microlipid
Fish oil
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2011-03-02
Enrollment: 40
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Necrotizing enterocolitis (NEC) and intestinal perforation are common in premature infants. Often surgery is needed to remove the dead bowel and create an ostomy (a temporary intestinal opening on the infant's abdomen). Infants with ostomies cannot digest and absorb food well, and must receive nutrition through the blood stream, i.e. parental nutrition (PN). However, prolonged dependence on PN can severely damage the liver and gut. Therefore, giving nutrition through the gut, i.e. enteral nutrition, is the primary treatment for infants with ostomies.

Enteral fats, especially polyunsaturated fatty acids (PUFA), are most beneficial in stimulating gut mucosal adaptation, which begins 24 to 48 hours following bowel resection. In addition, the premature intestine has a rapid growth rate. It is likely that the current clinical practice of giving a relatively low-fat diet to infants with ostomies may not meet their high metabolic needs.

The investigators hypothesize that increasing dietary fat content by early supplementation with MicroLipid® (ML, n-6 PUFA) and fish oil (FO, n-3 PUFA) to preserve the proper balance of n-6 and n-3 PUFA, may (i) improve bowel adaptation and infant growth; (ii) reduce the use of PN; and (iii) prevent liver damage and/or cholestasis (jaundice) in infants with ostomies.

Detailed description: It is an interventional randomized open-labeled controlled trial with two groups:

Treatment group: early supplementation of enteral lipid with ML and FO; Control group: routine care.

The primary goal of this study is to obtain pilot data that will inform the subsequent design and execution of a large, randomized trial which will test the hypothesis that infants with short bowel syndrome or ostomy will experience beneficial growth effects from enteral nutrition supplemented with balanced n6/n-3 PUFA, a simple, inexpensive and noninvasive intervention. This pilot study will confirm the safety of PUFA supplemented enteral nutrition, establish the length and amount of enteral versus parenteral nutrition required, and determine the impact on infant growth and intestinal adaptation by measuring expression of four key genes that play a crucial role in intestinal adaptation.

Eligibility criteria: Inclusion Criteria:

* infants (age range: newborn to 2-month-old) who are admitted to BCH NICU with a jejunostomy or ileostomy (from surgical intervention for NEC, bowel perforation, midgut volvulus (twisted bowel), atresia or other gastrointestinal surgery);
* who are expected to need full or partial PN for at least 21days from the day of enterostomy placement; and
* have received enteral feedings ≤ 4 days since enterostomy placement

Exclusion Criteria:

* infant with colostomy;
* infants with enterostomy but

  * unable to obtain written informed consent from parent;
  * presence of congenital liver or renal, or metabolic diseases; and
  * ostomy caused by gastroschisis, omphalocele, imperforate anus, and perinatal asphyxia
  * unable to initiate enteral feeds after 28 days of ostomy placement.

Primary outcomes:
measure: Average duration of exposure to PN (including Intralipid, IL) between the initial feeding and bowel reanastomosis
timeFrame: up to three years
Secondary outcomes:
measure: Average weight gain (g/day)from initiating feeding to reanastomosis
timeFrame: up to three years
measure: Average level of conjugated bilirubin and ostomy output of infants receiving ML/FO to the group receiving usual care between the initial feeding after placement of ostomy and reanastomosis
timeFrame: up to three years
measure: Dietary fat and protein absorption, from initiating feeding to reanastomosis
timeFrame: up to three years
measure: Expression of four key genes that play a crucial role in intestinal adaptation
timeFrame: up to four years
measure: Neurodevelopment outcomes and growth in the infants receiving ML/FO vs. in the infants receiving usual care at the 18-24 month of age.
timeFrame: up to 4.5 years
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: WFUHS Brenner Children's Hospital NICU
state: North Carolina
Study officials:
affiliation: Wake Forest Univeristy Health Science
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 Yang Q. 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.
citation: Younge N, Yang Q, Seed PC. Enteral High Fat-Polyunsaturated Fatty Acid Blend Alters the Pathogen Composition of the Intestinal Microbiome in Premature Infants with an Enterostomy. J Pediatr. 2017 Feb;181:93-101.e6. doi: 10.1016/j.jpeds.2016.10.053. Epub 2016 Nov 15.
citation: Yang Q, Ayers K, Chen Y, O'Shea TM. Early enteral fat supplementation improves protein absorption in premature infants with an enterostomy. Neonatology. 2014;106(1):10-6. doi: 10.1159/000357554. Epub 2014 Mar 6.