Clinical trial NCT03555019: Nutrition Therapy in the Immature Infant (ImNuT)
Official title: Effects of Nutrition Therapy on Growth, Inflammation and Metabolism in Immature Infants; a Double-blind Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Immature Infant
Essential Fatty Acid Deficiency
Keywords: Brain maturation
Postnatal growth
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Oslo
name: Umeå University
name: University of Geneva, Switzerland
First posted: 2018-06-13
Enrollment: 121
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized-controlled. Parallel group, single center trial
Primary purpose: SUPPORTIVE_CARE

Brief summary: The primary objective of this double-blind randomized study is to assess the effects of an early, enhanced supply of the essential fatty acids (FAs) arachidonic acid (ARA) and docosahexaenoic acid (DHA) on brain maturation, clinical outcomes and quality of growth in immature infants (gestational age \<29 weeks) as compared to standard nutrient supply.

Detailed description: This is a double-blind randomized study. 172 preterm infants with gestational age \< 29 weeks will be enrolled. The intervention group will receive enteral supplementation with essential fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA). The control group will receive standard supplementation with medium-chain triglycerides (MCT-oil). The main hypothesis is that early, enhanced supply of ARA and DHA will improve brain growth and maturation, as compared to standard nutrient supply. Secondary hypotheses are that early, enhanced supply of ARA and DHA will improve quality of growth and cognitive development as well as reduce the frequency of inflammation-related neonatal comorbidities and long-term cardiovascular disease risk. Primary endpoint will be assessed by magnetic resonance imaging (MRI) of the brain at term equivalent age.

Eligibility criteria: Inclusion Criteria:

* Extremely preterm infants born at Oslo University Hospital (OUH)
* Gestational age (GA) \< 29 weeks
* Less than 48 hours of age at inclusion
* Signed informed consent and expected Cooperation of the patients for the treatment and follow up must be obtained and documented according to good clinical practice (GCP) and national/local regulations

Exclusion Criteria:

* Major congenital malformations which will affect growth and development
* Chromosomal abnormalities and other genetic diseases
* Critical illness with short life expectancy as defined by the study physician

Primary outcomes:
measure: Brain maturation assessed by magnetic resonance imaging (MRI)
timeFrame: 40 weeks postmenstrual age (PMA)
Secondary outcomes:
measure: Weight gain
timeFrame: Weight will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age.
measure: Growth
timeFrame: Length and HC will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age.
measure: Body composition
timeFrame: At 36 weeks PMA, 3 months and 2 years corrected age
measure: Neonatal morbidities associated with inflammation
timeFrame: From birth til 36 weeks PMA
measure: Cerebral Background Activity evaluated by Electroencephalogram (EEG)
timeFrame: First week of life, 36 weeks PMA and 2 years corrected age (CA)
measure: Neurodevelopment assessed by standardized motor and cognitive tests
timeFrame: 2 years corrected age (CA)
measure: Lung function evaluated by tidal breathing measurements
timeFrame: 36 weeks PMA, 3 months and 2 years CA
measure: Cardiovascular Health assessed by echocardiography
timeFrame: First week of life, 2nd week of life, at 36 weeks PMA and 2 years CA
measure: Blood pressure
timeFrame: First week of life and at 36 weeks PMA and 2 years CA
measure: Fatty acid (FA) profiles in blood
timeFrame: From birth until 36 weeks PMA
measure: Markers of inflammation
timeFrame: From birth until 36 weeks PMA
measure: Markers of metabolic status
timeFrame: From birth until 36 weeks PMA
measure: Markers of nutritional status in blood
timeFrame: From birth until 36 weeks PMA
measure: Micronutrient content in urine
timeFrame: From birth until 36 weeks PMA
measure: Evaluation of nutrient composition of expressed breast milk
timeFrame: From birth until 36 weeks PMA
measure: Gut microbiota
timeFrame: From birth until 36 weeks PMA
measure: Inflammatory markers in sputum
timeFrame: From birth until 36 weeks PMA
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Departement of Neonatal Intensive care, Oslo University Hospital
name: Tom Stiris, MD, ass prof
role: STUDY_DIRECTOR
References:
citation: Hortensius LM, Hellstrom W, Savman K, Heckemann RA, Bjorkman-Burtscher IM, Groenendaal F, Andersson MX, Nilsson AK, Tataranno ML, van Elburg RM, Hellstrom A, Benders MJNL. Serum docosahexaenoic acid levels are associated with brain volumes in extremely preterm born infants. Pediatr Res. 2021 Dec;90(6):1177-1185. doi: 10.1038/s41390-021-01645-w. Epub 2021 Aug 14.
citation: Wendel K, Pfeiffer HCV, Fugelseth DM, Nestaas E, Domellof M, Skalhegg BS, Elgstoen KBP, Rootwelt H, Pettersen RD, Pripp AH, Stiris T, Moltu SJ; ImNuT Collaboration Group. Effects of nutrition therapy on growth, inflammation and metabolism in immature infants: a study protocol of a double-blind randomized controlled trial (ImNuT). BMC Pediatr. 2021 Jan 7;21(1):19. doi: 10.1186/s12887-020-02425-x.