Nutrition Therapy in the Immature Infant (ImNuT)

Essential Fatty Acid Deficiency Clinical Trial

— ImNuT  

Official title:

Effects of Nutrition Therapy on Growth, Inflammation and Metabolism in Immature Infants; a Double-blind Randomized, Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03555019
• Other study ID #: 2016-003700-31
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 13, 2018
• Est. completion date: May 30, 2029

Study information

• Verified date: September 2021
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 121
• Est. completion date: May 30, 2029
• Est. primary completion date: May 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 48 Hours

Eligibility

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

Related Conditions & MeSH terms

• Essential Fatty Acid Deficiency
• Immature Infant

Intervention

Dietary Supplement:
• Formulaid
Supplementation with ARA and DHA
• MCT-oil
Supplementation with medium chain fatty acids

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (4)

Lead Sponsor	Collaborator
Oslo University Hospital	Umeå University, University of Geneva, Switzerland, University of Oslo

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain maturation assessed by magnetic resonance imaging (MRI)	MRI with spectroscopy (MRS) and diffusion tensor imaging (DTI) will be used to examine myelinisation and quantification of anatomical structures as well as neuronal integrity and inflammation	40 weeks postmenstrual age (PMA)
Secondary	Weight gain	Weight measurements, including weight nadir.	Weight will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age.
Secondary	Growth	Length and head circumference (HC).	Length and HC will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age.
Secondary	Body composition	Body composition will be assessed using PEA POD, an air displacement plethysmography system and Dexa Scan.	At 36 weeks PMA, 3 months and 2 years corrected age
Secondary	Neonatal morbidities associated with inflammation	Bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), white matter injury (WMI) of the brain, and late onset septicemia	From birth til 36 weeks PMA
Secondary	Cerebral Background Activity evaluated by Electroencephalogram (EEG)	EEG maturational changes will be examined as a function of time and as a function of gestational age	First week of life, 36 weeks PMA and 2 years corrected age (CA)
Secondary	Neurodevelopment assessed by standardized motor and cognitive tests	Evaluation of psychomotor development by performing Bayley III and a standardized neurological examination	2 years corrected age (CA)
Secondary	Lung function evaluated by tidal breathing measurements	Tidal breathing measurements include tidal volume, respiratory rate, minute ventilation and fraction of expiratory time to peak tidal expiratory flow to total expiratory time	36 weeks PMA, 3 months and 2 years CA
Secondary	Cardiovascular Health assessed by echocardiography	Echocardiography will be used to follow the transition from fetal to completed neonatal circulation, to measure superior vena cava flow, and to study mycardial function by the use of conventional two-dimensional echocardiography and tissue Doppler imaging.	First week of life, 2nd week of life, at 36 weeks PMA and 2 years CA
Secondary	Blood pressure	Measurements of systolic, diastolic and mean pressure	First week of life and at 36 weeks PMA and 2 years CA
Secondary	Fatty acid (FA) profiles in blood	Repeated dried blood spots (DBS) samples with approximately 10 µL blood will be collected for FA analyses. These analyses are important for assessing efficacy and protocol compliance. We will also collect 10 µL of fullblood for assessment of total lipid profile (Lipidomics).	From birth until 36 weeks PMA
Secondary	Markers of inflammation	Inflammation panels will be used to assess markers of inflammation in fullblood and sputum	From birth until 36 weeks PMA
Secondary	Markers of metabolic status	Metabolic pathway analyses (http://omictools.com/metabolic-pathways-category) will be performed to analyse and describe the metabolic conditions of the infants during hospitalization. Metabolites outside the standard clinical chemistry parameters will also be investigated ("untargeted metabolomics). Metabolomics will be performed by the use of dried blood spot samples	From birth until 36 weeks PMA
Secondary	Markers of nutritional status in blood	The concentrations of electrolytes, minerals, albumin, alkaline phosphatase, vitamin A and D will be assessed regularly during hospitalization	From birth until 36 weeks PMA
Secondary	Micronutrient content in urine	Spot urine will be obtained regularly to study the changes in electrolyte- and mineral homeostasis during the first week of life as well as during the phase of steady growth	From birth until 36 weeks PMA
Secondary	Evaluation of nutrient composition of expressed breast milk	Repeated samples of breast milk will be collected for FA analyses, macronutrient content and vitamin A	From birth until 36 weeks PMA
Secondary	Gut microbiota	Repeated samples of feces will be used to study the early fecal microbiota	From birth until 36 weeks PMA
Secondary	Inflammatory markers in sputum	We will analyze the Expression of a standardized panel of inflammatory markers in collected laryngeal or tracheal secretion	From birth until 36 weeks PMA