PrematurityPhase 2EMLFO-2NCT01674478
Early Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies
A Phase 2 study testing Microlipid with fish oil and Microlipid in people with Prematurity and Intestine Perforation, run by Wake Forest University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 day to 2 months
- Conditions the study is for
- Prematurity, Intestine Perforation, Necrotizing Enterocolitis (NEC)
- What is being tested?
- Microlipid with fish oil and Microlipid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to 17 Mar 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 2 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- infants (age range: newborn to ≤ 2-month-old) whose birth weight are ≤ 1250g;
- who are admitted to BCH NICU for surgical intervention for NEC or small intestine perforation and then to have a jejunostomy or ileostomy;
- who are expected to need full or partial PN for at least 21days from the day of ostomy placement; and
- who have received enteral feedings ≤ 4 days since ostomy placement.
Who cannot join
- infant with birth weight > 1250g;
- infant with colostomy;
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Health Science
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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.
- Conditions
- Prematurity, Intestine Perforation, Necrotizing Enterocolitis (NEC), Short Bowel Syndrome (SBS)
- Being tested
- Microlipid with fish oil, Microlipid
- Keywords
- NEC, SBS, enterostomy, fish oil, Microlipid, Intralipid,, enteral fat
- Medical subject headings
- Premature Birth, Intestinal Perforation, Enterocolitis, Necrotizing, Short Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microlipid with fish oilDietary supplement
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.
MicrolipidDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Microlipid with fish oil group | Experimental | This group will be given early enteral lipid supplementation with Microlipid and fish oil. Receives: Dietary Supplement: Microlipid with fish oil |
| Microlipid group | Active comparator | This group will be given early enteral lipid supplementation only with Microlipid. Receives: Dietary Supplement: Microlipid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 2 years and 5 months
Secondary outcomes (2)
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
Measured: 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
Measured: 2 years and 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2012 (estimated)
- Study startOct 2012
- Primary completion17 Mar 2015
- Study completion17 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Qing Yang, MD, PhD, Principal investigator, WFUHS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01674478
- Sponsor's protocol ID
- IRB00021481
- Acronym
- EMLFO-2
- Status last verified
- Nov 2018
- First submitted
- 18 Aug 2012
- Last updated
- 4 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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 20531250Yang 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 22447320Yang 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 20980771Woods 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.
PubMed 23453547
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Supplementation of Enteral Microlipid With and Without Fish Oil in Premature Infants With Enterostomies
- ClinicalTrials.gov ID
- NCT01674478
- Acronym / sponsor ID
- EMLFO-2 / IRB00021481
- Conditions
- Prematurity, Intestine Perforation, Necrotizing Enterocolitis (NEC), Short Bowel Syndrome (SBS)
- Keywords
- NEC, SBS, enterostomy, fish oil, Microlipid, Intralipid,, enteral fat
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Study start
- Oct 2012 (actual)
- Primary completion
- 17 Mar 2015 (actual)
- Study completion
- 17 Mar 2015 (actual)
- First posted
- 28 Aug 2012 (estimated)
- Results
- Posted 4 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Microlipid with fish oil group | Experimental | Dietary Supplement: Microlipid with fish oilThis group will be given early enteral lipid supplementation with Microlipid and fish oil. |
| Microlipid group | Active comparator | Dietary Supplement: MicrolipidThis group will be given early enteral lipid supplementation only with Microlipid. |
Who may qualify
- Ages
- 1 day to 2 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- infants (age range: newborn to ≤ 2-month-old) whose birth weight are ≤ 1250g;
- who are admitted to BCH NICU for surgical intervention for NEC or small intestine perforation and then to have a jejunostomy or ileostomy;
- who are expected to need full or partial PN for at least 21days from the day of ostomy placement; and
- who have received enteral feedings ≤ 4 days since ostomy placement.
Key exclusion criteria (7 listed)
- infant with birth weight > 1250g;
- infant with colostomy;
- infants with enterostomy but
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Microlipid with fish oilFish 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. | Dietary supplement | Microlipid with fish oil group |
| MicrolipidA 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. | Dietary supplement | Microlipid group |
Primary outcome
The Serum Biomarkers of Inflammatory Cytokines
Time frame: 2 years and 5 months
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
The Serum Biomarkers of Oxidative Stress
Time frame: 2 years and 5 months
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 secondary outcomes
The Average Enteral Calorie (Total Calorie) Intake Before Reanast
Time frame: 2 years and 5 months
The Average Weight Gain (g/Day) After Reanastomosis
Time frame: 2 years and 5 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20531250Yang 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.
- Background: PubMed 22447320Yang 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.
- Results publication: PubMed 20980771Yang 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.
- Results publicationWoods 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.
- Results publication: PubMed 23453547Yang 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Qing Yang, MD, PhD principal investigator
WFUHS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Microlipid with fish oil and Microlipid in people with Prematurity and Intestine Perforation, run by Wake Forest University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Serum Biomarkers of Inflammatory Cytokines (time frame: 2 years and 5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01674478, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2018.