Nutrition Therapy in the Immature Infant (ImNuT) (ImNuT)

• ClinicalTrials.gov Identifier: NCT03555019
• Recruitment Status: Active, not recruiting
• First Posted: June 13, 2018
• Last Update Posted: September 8, 2021
• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo; Umeå University; University of Geneva, Switzerland
• Information provided by (Responsible Party): Sissel Jennifer Moltu, Oslo University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immature Infant; Essential Fatty Acid Deficiency	Dietary Supplement: Formulaid; Dietary Supplement: MCT-oil	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Double-blind, randomized-controlled. Parallel group, single center trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Effects of Nutrition Therapy on Growth, Inflammation and Metabolism in Immature Infants; a Double-blind Randomized, Controlled Trial
• Actual Study Start Date: April 13, 2018
• Actual Primary Completion Date: May 28, 2021
• Estimated Study Completion Date: May 30, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: Formulaid; The intervention group will receive enteral supplementation with Formulaid containing ARA and DHA at a ratio of 2:1, from birth until 36 weeks PMA	Dietary Supplement: Formulaid; Supplementation with ARA and DHA
Active Comparator: MCT-oil; The control group will receive enteral supplementation with MCT oil containing coconut and/or palm kern oil, from birth until 36 weeks PMA	Dietary Supplement: MCT-oil; Supplementation with medium chain fatty acids

Outcome Measures

Primary Outcome Measures :

1. Brain maturation assessed by magnetic resonance imaging (MRI) [ Time Frame: 40 weeks postmenstrual age (PMA) ]
   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

Secondary Outcome Measures :

1. Weight gain [ Time Frame: Weight will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age. ]
   Weight measurements, including weight nadir.
2. Growth [ Time Frame: Length and HC will be recorded until 36 weeks PMA and at 3, 6, 12 and 24 months and 8 years corrected age. ]
   Length and head circumference (HC).
3. Body composition [ Time Frame: At 36 weeks PMA, 3 months and 2 years corrected age ]
   Body composition will be assessed using PEA POD, an air displacement plethysmography system and Dexa Scan.
4. Neonatal morbidities associated with inflammation [ Time Frame: From birth til 36 weeks PMA ]
   Bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), white matter injury (WMI) of the brain, and late onset septicemia
5. Cerebral Background Activity evaluated by Electroencephalogram (EEG) [ Time Frame: First week of life, 36 weeks PMA and 2 years corrected age (CA) ]
   EEG maturational changes will be examined as a function of time and as a function of gestational age
6. Neurodevelopment assessed by standardized motor and cognitive tests [ Time Frame: 2 years corrected age (CA) ]
   Evaluation of psychomotor development by performing Bayley III and a standardized neurological examination
7. Lung function evaluated by tidal breathing measurements [ Time Frame: 36 weeks PMA, 3 months and 2 years CA ]
   Tidal breathing measurements include tidal volume, respiratory rate, minute ventilation and fraction of expiratory time to peak tidal expiratory flow to total expiratory time
8. Cardiovascular Health assessed by echocardiography [ Time Frame: First week of life, 2nd week of life, at 36 weeks PMA and 2 years CA ]
   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.
9. Blood pressure [ Time Frame: First week of life and at 36 weeks PMA and 2 years CA ]
   Measurements of systolic, diastolic and mean pressure
10. Fatty acid (FA) profiles in blood [ Time Frame: From birth until 36 weeks PMA ]
    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).
11. Markers of inflammation [ Time Frame: From birth until 36 weeks PMA ]
    Inflammation panels will be used to assess markers of inflammation in fullblood and sputum
12. Markers of metabolic status [ Time Frame: From birth until 36 weeks PMA ]
    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
13. Markers of nutritional status in blood [ Time Frame: From birth until 36 weeks PMA ]
    The concentrations of electrolytes, minerals, albumin, alkaline phosphatase, vitamin A and D will be assessed regularly during hospitalization
14. Micronutrient content in urine [ Time Frame: From birth until 36 weeks PMA ]
    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
15. Evaluation of nutrient composition of expressed breast milk [ Time Frame: From birth until 36 weeks PMA ]
    Repeated samples of breast milk will be collected for FA analyses, macronutrient content and vitamin A
16. Gut microbiota [ Time Frame: From birth until 36 weeks PMA ]
    Repeated samples of feces will be used to study the early fecal microbiota
17. Inflammatory markers in sputum [ Time Frame: From birth until 36 weeks PMA ]
    We will analyze the Expression of a standardized panel of inflammatory markers in collected laryngeal or tracheal secretion

Eligibility Criteria

• Ages Eligible for Study: up to 48 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Norway

Oslo University Hospital

Oslo, Norway

Sponsors and Collaborators

Oslo University Hospital

University of Oslo

Umeå University

University of Geneva, Switzerland

Investigators

• Study Director: Tom Stiris, MD, ass prof; Departement of Neonatal Intensive care, Oslo University Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Sissel Jennifer Moltu, MD, PhD, Principal Investigator, Oslo University Hospital
• ClinicalTrials.gov Identifier: NCT03555019
• Other Study ID Numbers: 2016-003700-31
• First Posted: June 13, 2018
• Last Update Posted: September 8, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data will be available within 6 months of study completion

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sissel Jennifer Moltu, Oslo University Hospital:

Brain maturation; Postnatal growth