Necrotizing EnterocolitisPhase 1/2NCT01745510
Enteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates
A Phase 1/2 study testing Docosahexaenoic acid (DHA) in people with Necrotizing Enterocolitis, run by Coordinación de Investigación en Salud, Mexico at 1 site in Mexico.
Trial summary
The purpose of this study is to determine whether docosahexaenoic acid is effective in the prevention or reducing severity of necrotizing enterocolitis (NEC) in preterm neonates < 1500 g at birth who are starting enteral feeding. Read more about this study
- Who is it for?
- Ages 60 minutes to 2 weeks
- Conditions the study is for
- Necrotizing Enterocolitis
- What is being tested?
- Docosahexaenoic acid (DHA)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 225 participants
- Where
- 1 siteMexico
- Study dates
- Oct 2012to Oct 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 60 minutes to 2 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Birth weight lower than 1500 g
- Adequate weight for gestational age
- Clinically stable to begin enteral feeding
- Written informed consent by both parents plus the sign of two witnesses
Who cannot join
- Clinical and biochemical data of inflammatory response such as body core temperature altered, cardiac and respiratory frequency -low or high according to age-, leucocytosis or leucopenia, taking into account the thresholds reported by Goldstein in Pediatric Critical Care Medicine 2005 Vol 6 N°1.
- Persistent bleeding at any level
- Mother taking n-3 supplements and planning to breastfed
- Parents who decline the authorization for participating in the study
- Early discharge to other hospital outside the metropolitan area
- Persistent vomiting
- Receiving medication to avoid coagulation
- Gastrointestinal malformations
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Unit of Medical Research in Nutrition, Pediatric Hospital, IMSS
Mexico City, Mexico City, 06720
About this study
Official title: Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates
- The purpose of this study is to determine whether docosahexaenoic acid is effective in the prevention or reducing severity of necrotizing enterocolitis (NEC) in preterm neonates < 1500 g at birth who are starting enteral feeding.
- if NEC is prevented, this study will measure whether hospital stay is also reduced in neonates who receive Docosahexaenoic acid (DHA)
Read the detailed description
- Preterm neonates with birth weight less than 1500 g are in higher risk to develop NEC.
- NEC is an inflammatory condition that:
- Is the medical urgency most frequent of gastrointestinal tube that requires neonatal intensive care
- may perforate infant´s bowel requiring surgery from 20% to 60% of the cases
- may cause infant's death in 20% to 42% of the cases.
- has no adequate treatment worldwide, therefore prevention is needed
- DHA by enteral feeding has been administrated by our research group to attenuate inflammatory response in septic and surgical neonates.
- Our results showed:
- lower Interleukin(IL)-1 beta in septic neonates, but in surgical neonates, they also showed less IL-6 and anti-inflammatory cytokines IL-10 and IL-1ra, after adjusting by confounders
- increased weight, length and fat mass gain in septic neonates
- decreased organic failures in surgical neonates, and
- lower stay at neonatal intensive care in surgical neonates
DHA has not been used as unique intervention at a high but physiological dose; in addition, our previous results found an anti-inflammatory effect in neonates.Therefore, we expect that preterm infants may have a reduced bowel inflammatory response and lower NEC events and or severity
- Conditions
- Necrotizing Enterocolitis
- Being tested
- Docosahexaenoic acid (DHA), Placebo
- Keywords
- docosahexaenoic acid, n-3 fatty acids, necrotizing enterocolitis, preterm infants
- Medical subject headings
- Enterocolitis, Necrotizing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Docosahexaenoic acid (DHA)Dietary supplement
Also called n-3 Fatty Acids
Docosahexaenoic acid from algae source
PlaceboDietary supplement
Also called Sunflower oil, Placebo for DHA intervention
Placebo was designed to mimic the color and consistence of the oil that contains DHA
| Study group | Role | What they receive |
|---|---|---|
| DHA Group | Experimental | DHA Group will receive 75 milligrams of docosahexaenoic acid (DHA) per kilogram of their baseline weight.
They will receive one dose, administered by enteral feeding every 24 h during 14 days Receives: Dietary Supplement: Docosahexaenoic acid (DHA) |
| Control Group (Placebo) | Placebo comparator | Control group will receive sunflower oil which is the excipient of the DHA in this study.
They will receive one dose every 24 h during 14 days. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Necrotizing enterocolitis (NEC)
Neonates will receive enteral DHA at beginning of their first enteral feeding and NEC will be diagnosed during hospital stay, measured as presence or absence, as well as severity of NEC by Bell's score.
Measured: Patients will be followed for the duration of hospital stay, an expected average of 6 weeks
Secondary outcomes (7)
Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10
Plasma cytokines will be determined before to the beginning of the enteral feeding (baseline) and if the infant develop confirmed or severe NEC. Cytokines will be measured by a multiplex kit in picograms/mL.
Measured: At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria
Hospital stay
Hospital stay includes intensive stay care and preterm service (where clinically stable babies are attended) until they are discharged from the hospital to home, in days.
Measured: The duration of hospital stay, an expected average of 6 weeks
Growth velocity in weight
Gain of weight in g/kd/day, measured with an electronic scale every week until hospital discharge or 40 weeks of corrected gestational age
Measured: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Growth velocity in length and head circumference
Gain of recumbent length and and head circumference in cm/week measured every 2 weeks until hospital discharge or 40 weeks of corrected gestational age. For measuring length we will use an infantometer and for head circumference we will use a glass fiber tape.
Measured: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Growth velocity in skin folds
Gain of bicipital, tricipital, suprailiac and subscapular skin folds in mm/week measured every 2 weeks, until hospital discharge or 40 weeks of corrected gestational age. We will use a glass fiber tape to measure it.
Measured: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Enteral tolerance
Registration of volume of the enteral intake every 24 h (ml/kg/day) until reach 150 ml/kg/day and being sustained or increased by enteral feeding with human milk or formula.
Measured: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
Enteral intolerance
Registration of number of patients with clinical signs of intolerance such as vomit, abnormal number of stool loss, abdominal distension, number of patients with medical indication to withdraw enteral feeding due clinical unstability and number of patients with use of medications related to enteral tolerance such as omeprazole, ranitidine, vitamins, iron, etc.
Measured: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2017
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Coordinación de Investigación en Salud, Mexico
- Sponsor type
- Other government
- Collaborators
- National Council of Science and Technology, Mexico
- Responsible party
- Principal investigator, Mariela Bernabe García, Coordinación de Investigación en Salud, Mexico
- Investigators
- Mariela Bernabe-Garcia, PhD, Principal investigator, Instituto Mexicano del Seguro Social
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745510
- Sponsor's protocol ID
- DHA-ECN
- Other IDs
- DHA, ECN and Preterm
- Status last verified
- Mar 2021
- First submitted
- 23 Nov 2012
- Last updated
- 24 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: This project has secondary outcomes that have not been analyzed; therefore, in this moment we decided not to share our database.
Publications
Lopez-Alarcon M, Bernabe-Garcia M, Del Prado M, Rivera D, Ruiz G, Maldonado J, Villegas R. Docosahexaenoic acid administered in the acute phase protects the nutritional status of septic neonates. Nutrition. 2006 Jul-Aug;22(7-8):731-7. doi: 10.1016/j.nut.2006.04.002. Epub 2006 Jun 5.
PubMed 16750345Lopez-Alarcon M, Bernabe-Garcia M, del Valle O, Gonzalez-Moreno G, Martinez-Basilea A, Villegas R. Oral administration of docosahexaenoic acid attenuates interleukin-1beta response and clinical course of septic neonates. Nutrition. 2012 Apr;28(4):384-90. doi: 10.1016/j.nut.2011.07.016. Epub 2011 Nov 12.
PubMed 22079797Bernabe-Garcia M, Lopez-Alarcon M, Villegas-Silva R, Mancilla-Ramirez J, Rodriguez-Cruz M, Maldonado-Hernandez J, Chavez-Rueda KA, Blanco-Favela F, Espinoza-Garcia L, Lagunes-Salazar S. Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study. Ann Nutr Metab. 2016;69(1):15-23. doi: 10.1159/000447498. Epub 2016 Jul 9.
PubMed 27394149Bernabe-Garcia M, Calder PC, Villegas-Silva R, Rodriguez-Cruz M, Chavez-Sanchez L, Cruz-Reynoso L, Mateos-Sanchez L, Lara-Flores G, Aguilera-Joaquin AR, Sanchez-Garcia L. Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial. Nutrients. 2021 Feb 17;13(2):648. doi: 10.3390/nu13020648.
PubMed 33671220
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates
- ClinicalTrials.gov ID
- NCT01745510
- Acronym / sponsor ID
- DHA-ECN
- Conditions
- Necrotizing Enterocolitis
- Keywords
- docosahexaenoic acid, n-3 fatty acids, necrotizing enterocolitis, preterm infants
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- Coordinación de Investigación en Salud, MexicoOther government
- Collaborators
- National Council of Science and Technology, Mexico
- Study start
- Oct 2012
- Primary completion
- Oct 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 10 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- The purpose of this study is to determine whether docosahexaenoic acid is effective in the prevention or reducing severity of necrotizing enterocolitis (NEC) in preterm neonates < 1500 g at birth who are starting enteral feeding.
- if NEC is prevented, this study will measure whether hospital stay is also reduced in neonates who receive Docosahexaenoic acid (DHA)
Detailed description
- Preterm neonates with birth weight less than 1500 g are in higher risk to develop NEC.
- NEC is an inflammatory condition that:
- Is the medical urgency most frequent of gastrointestinal tube that requires neonatal intensive care
- may perforate infant´s bowel requiring surgery from 20% to 60% of the cases
- may cause infant's death in 20% to 42% of the cases.
- has no adequate treatment worldwide, therefore prevention is needed
- DHA by enteral feeding has been administrated by our research group to attenuate inflammatory response in septic and surgical neonates.
- Our results showed:
- lower Interleukin(IL)-1 beta in septic neonates, but in surgical neonates, they also showed less IL-6 and anti-inflammatory cytokines IL-10 and IL-1ra, after adjusting by confounders
- increased weight, length and fat mass gain in septic neonates
- decreased organic failures in surgical neonates, and
- lower stay at neonatal intensive care in surgical neonates
DHA has not been used as unique intervention at a high but physiological dose; in addition, our previous results found an anti-inflammatory effect in neonates.Therefore, we expect that preterm infants may have a reduced bowel inflammatory response and lower NEC events and or severity
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.
| Arm | Type | Receives |
|---|---|---|
| DHA Group | Experimental | Dietary Supplement: Docosahexaenoic acid (DHA)DHA Group will receive 75 milligrams of docosahexaenoic acid (DHA) per kilogram of their baseline weight. They will receive one dose, administered by enteral feeding every 24 h during 14 days |
| Control Group (Placebo) | Placebo comparator | Dietary Supplement: PlaceboControl group will receive sunflower oil which is the excipient of the DHA in this study. They will receive one dose every 24 h during 14 days. |
Who may qualify
- Ages
- 60 minutes to 2 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Birth weight lower than 1500 g
- Adequate weight for gestational age
- Clinically stable to begin enteral feeding
- Written informed consent by both parents plus the sign of two witnesses
Key exclusion criteria (8 listed)
- Clinical and biochemical data of inflammatory response such as body core temperature altered, cardiac and respiratory frequency -low or high according to age-, leucocytosis or leucopenia, taking into account the thresholds reported by Goldstein in Pediatric Critical Care Medicine 2005 Vol 6 N°1.
- Persistent bleeding at any level
- Mother taking n-3 supplements and planning to breastfed
- Parents who decline the authorization for participating in the study
- Early discharge to other hospital outside the metropolitan area
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 |
|---|---|---|
| Docosahexaenoic acid (DHA)Also: n-3 Fatty AcidsDocosahexaenoic acid from algae source | Dietary supplement | DHA Group |
| PlaceboAlso: Sunflower oil, Placebo for DHA interventionPlacebo was designed to mimic the color and consistence of the oil that contains DHA | Dietary supplement | Control Group (Placebo) |
Primary outcome
Necrotizing enterocolitis (NEC)
Time frame: Patients will be followed for the duration of hospital stay, an expected average of 6 weeks
Neonates will receive enteral DHA at beginning of their first enteral feeding and NEC will be diagnosed during hospital stay, measured as presence or absence, as well as severity of NEC by Bell's score.
7 secondary outcomes
Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10
Time frame: At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria
Hospital stay
Time frame: The duration of hospital stay, an expected average of 6 weeks
Growth velocity in weight
Time frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Growth velocity in length and head circumference
Time frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Growth velocity in skin folds
Time frame: Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks
Enteral tolerance
Time frame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
Enteral intolerance
Time frame: During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2021.
- Background: PubMed 16750345Lopez-Alarcon M, Bernabe-Garcia M, Del Prado M, Rivera D, Ruiz G, Maldonado J, Villegas R. Docosahexaenoic acid administered in the acute phase protects the nutritional status of septic neonates. Nutrition. 2006 Jul-Aug;22(7-8):731-7. doi: 10.1016/j.nut.2006.04.002. Epub 2006 Jun 5.
- Background: PubMed 22079797Lopez-Alarcon M, Bernabe-Garcia M, del Valle O, Gonzalez-Moreno G, Martinez-Basilea A, Villegas R. Oral administration of docosahexaenoic acid attenuates interleukin-1beta response and clinical course of septic neonates. Nutrition. 2012 Apr;28(4):384-90. doi: 10.1016/j.nut.2011.07.016. Epub 2011 Nov 12.
- Background: PubMed 27394149Bernabe-Garcia M, Lopez-Alarcon M, Villegas-Silva R, Mancilla-Ramirez J, Rodriguez-Cruz M, Maldonado-Hernandez J, Chavez-Rueda KA, Blanco-Favela F, Espinoza-Garcia L, Lagunes-Salazar S. Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study. Ann Nutr Metab. 2016;69(1):15-23. doi: 10.1159/000447498. Epub 2016 Jul 9.
- Results publication: PubMed 33671220Bernabe-Garcia M, Calder PC, Villegas-Silva R, Rodriguez-Cruz M, Chavez-Sanchez L, Cruz-Reynoso L, Mateos-Sanchez L, Lara-Flores G, Aguilera-Joaquin AR, Sanchez-Garcia L. Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial. Nutrients. 2021 Feb 17;13(2):648. doi: 10.3390/nu13020648.
- Individual participant dataSharing planned: No. This project has secondary outcomes that have not been analyzed; therefore, in this moment we decided not to share our database.
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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.
Mariela Bernabe-Garcia, PhD principal investigator
Instituto Mexicano del Seguro Social
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Docosahexaenoic acid (DHA) in people with Necrotizing Enterocolitis, run by Coordinación de Investigación en Salud, Mexico at 1 site in Mexico.
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 8 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 24 Mar 2021. 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 Mexico. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Necrotizing enterocolitis (NEC) (time frame: Patients will be followed for the duration of hospital stay, an expected average of 6 weeks). 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 NCT01745510, which also lists 4 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 24 Mar 2021.