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CompletedNCT01306838EMLFOUpdated Aug 15, 2018

Early Provision of Enteral Microlipid and Fish Oil to Infants With Enterostomy

An Early Phase 1 interventional study of MicroLipid and fish oil and Routine care in Short Bowel Syndrome, Necrotizing Enterocolitis and Small Intestine Perforation, sponsored by Wake Forest University. Completed at 1 site in United States. Open to participants aged 1 Day to 60 Days. Per ClinicalTrials.gov, last updated 2018-08-15.

Sponsored by Wake Forest University · Early Phase 1, Interventional, and Other

Phase
Early Phase 1
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
1 Day to 60 Days
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Short Bowel Syndrome
  • Necrotizing Enterocolitis
  • Small Intestine Perforation

Keywords

  • Short bowel syndrome
  • Necrotizing enterocolitis
  • Small intestine perforation
  • Enterostomy
  • Intralipid
  • Microlipid
  • Fish oil
03

Who can participate

Ages eligible
1 Day to 60 Days
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Early Phase 1
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
40 participants (actual)

Study arms

  • Experimental
    Treatment

    The treatment arm is given early enteral supplementation with MicroLipid and Fish oil.

    Dietary Supplement: MicroLipid and fish oil

  • Active comparator
    Control Group

    Routine care

    Other: Routine care

Interventions

  • Dietary supplementMicroLipid and fish oil

    Infants in treatment arm will receive the same nutrition support as control group before they tolerate enteral feeding at 20 ml/kg/day. Then they will receive study oils when feeds reach 30 ml/kg/day.

  • OtherRoutine care

    Routine care

05

What researchers measure

Primary outcomes

  1. Average duration of exposure to PN (including Intralipid, IL) between the initial feeding and bowel reanastomosis

    We hypothesize that the average duration of exposure to PN/IL of the infants receiving ML/FO will be less than that of infants receiving usual care. The ratio of enteral to parenteral nutrition in the infants receiving ML/FO will be greater than that of infants receiving usual care.

    Time frame: up to three years

Secondary outcomes

  1. Average weight gain (g/day)from initiating feeding to reanastomosis

    We hypothesize that the average weight gain in infants receiving ML/FO will be greater than that of infants receiving usual care.

    Time frame: up to three years

  2. 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

    W hypothesize that the average level of conjugated bilirubin and ostomy output of infants receiving ML/FO will be less than that of infants receiving usual care.

    Time frame: up to three years

  3. Dietary fat and protein absorption, from initiating feeding to reanastomosis

    Twenty-four hour stool (from ostomy) will be collected once per week after initiating feeding. Fecal fat and protein will be measured. Dietary fat and protein absorption will be calculated by subtracting fecal fat or protein from enteral dietary fat or protein, respectively. We hypothesize that infants receiving enteral ML/FO will have higher dietary fat and protein absorption than infants receiving routine care from initiating feeding to reanastomosis.

    Time frame: up to three years

  4. Expression of four key genes that play a crucial role in intestinal adaptation

    RNA expression of four genes in small intestine, peptide YY (PYY), apical sodium dependent bile acid transport (ASBT), glucagon-like peptide-2 (GLP-2), and CD36 or fatty acid translocase (FAT), will be measured in both samples from stoma and distal mucous fistula sites.

    Time frame: up to four years

  5. Neurodevelopment outcomes and growth in the infants receiving ML/FO vs. in the infants receiving usual care at the 18-24 month of age.

    We hypothesize that the early supplement of enteral ML/FO will have no adverse effect on the neurodevelopment outcomes and growth in the infants receiving ML/FO comparing to the infants receiving usual care at the 18-24 month of age.

    Time frame: up to 4.5 years

06

Study locations

1 site
  • WFUHS Brenner Children's Hospital NICU
    Winston-Salem, North Carolina 27157, United States
07

References and documents

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. PubMed 20531250 ↗
  • 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. PubMed 22447320 ↗
  • 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. PubMed 20980771 ↗
  • 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
  • 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. PubMed 23453547 ↗
  • 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. PubMed 27856001 ↗
  • 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. PubMed 24603562 ↗
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Registry details

Key details

Study ID
NCT01306838
Lead sponsor
Wake Forest University
Responsible party
Sponsor
First posted
Mar 2, 2011
Start date
Oct 2009
Primary completion
Oct 2014
Completion
Oct 2014
Last update
Aug 15, 2018

Study contacts

Qing Yang, MD, PhD
principal investigator · Wake Forest Univeristy Health Science

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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