Enteral Administration of Docosahexaenoic Acid to Prevent Necrotizing Enterocolitis in Preterm Neonates

Sponsor

Coordinación de Investigación en Salud, Mexico (Other)

Overall Status

Completed

CT.gov ID

NCT01745510

Collaborator

National Council of Science and Technology, Mexico (Other)

225

Enrollment

Location

Arms

Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.
if NEC is prevented, this study will measure whether hospital stay is also reduced in neonates who receive Docosahexaenoic acid (DHA)

Condition or Disease	Intervention/Treatment	Phase
Necrotizing Enterocolitis	Dietary Supplement: Docosahexaenoic acid (DHA) Dietary Supplement: Placebo	Phase 1/Phase 2

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

Study Type:

Interventional

Actual Enrollment :

225 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.The intervention was the docosahexaenoic acid, a nutraceutical derived from the omega 3 fatty acids.

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Masking Description:

Intervention was blinded through assinging a code, printed and saved into opaque envelopes did it by a researcher who did not participate in the fieldwork. Randomization was carried out through the Random Allocation Software v.1

Primary Purpose:

Prevention

Official Title:

Efficacy of Enteral Administration of the Docosahexaenoic Acid on Necrotizing Enterocolitis, Cytokines and Hospital Stay in Preterm Neonates

Study Start Date :

Oct 1, 2012

Actual Primary Completion Date :

Oct 1, 2017

Actual Study Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DHA Group 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	Dietary Supplement: Docosahexaenoic acid (DHA) Docosahexaenoic acid from algae source Other Names: n-3 Fatty Acids
Placebo Comparator: Control Group (Placebo) 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.	Dietary Supplement: Placebo Placebo was designed to mimic the color and consistence of the oil that contains DHA Other Names: Sunflower oil, Placebo for DHA intervention

Arm

Intervention/Treatment

Experimental: DHA Group

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

Dietary Supplement: Docosahexaenoic acid (DHA)

Docosahexaenoic acid from algae source

Other Names:

n-3 Fatty Acids

Placebo Comparator: Control Group (Placebo)

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.

Dietary Supplement: Placebo

Placebo was designed to mimic the color and consistence of the oil that contains DHA

Other Names:

Sunflower oil, Placebo for DHA intervention

Outcome Measures

Primary Outcome Measures

Necrotizing enterocolitis (NEC) [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.

Secondary Outcome Measures

Cytokines Interleukin (IL)-1 beta, Tumoral necrosis factor (TNF)-alpha, IL-6, IL-10 [At baseline and a second measurement only if they develop confirmed or severe NEC according to Bell's criteria]
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.
Hospital stay [The duration of hospital stay, an expected average of 6 weeks]
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.
Growth velocity in weight [Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks]
Gain of weight in g/kd/day, measured with an electronic scale every week until hospital discharge or 40 weeks of corrected gestational age
Growth velocity in length and head circumference [Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks]
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.
Growth velocity in skin folds [Throughout hospital stay as part of nutritional follow-up of the care unit, an expected average of 4 weeks]
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.
Enteral tolerance [During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks]
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.
Enteral intolerance [During their hospital stay until reach 150 ml/kg/day, in average 2 to 5 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Minutes to 2 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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