Clinical trial NCT03374033: High Protein and High Energy Intakes and Physical Activity on Growth of Extremely Low Birth Weight Infants
Official title: Effect of High Protein and High Energy Intakes and Physical Activity on Growth and Body Composition of Extremely Low Birth Weight Infants: a Randomised Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infant, Very Low Birth Weight
Keywords: Preterm infants, growth, nutrition, physical activity
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
First posted: 2017-12-15
Enrollment: 200
Sex: ALL
Minimum age (years): 24
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to evaluate the effect of increasing amino acid and energy intake during parenteral and enteral nutrition with and without the stimulation of the infant's physical activity, on growth of extremely low birth weight infants .

Detailed description: Increasing protein and energy intake above the anabolic capacity of a given individual may result in increased lipogenesis and excessive fat deposition. Adults with reduced mobility or with neuromuscular conditions will develop excessive fat deposition if they receive normal to high protein and energy intakes. Excessive fat deposition have been demonstrated in preterm infants receiving high energy intakes. Given that physical activity in preterms is often reduced for the prematurity itself, the associated sickness and the numerous medications, the investigators speculate that physical stimulation may have a beneficial effect on protein accretion and on lean mass accretion. The investigators further hypothesize that today's recommended daily intakes of proteins and energy cannot be fully incorporated into lean body mass without a concomitant physical activity. In spite of the fact that this notion is well accepted in adult physiology and in the elderly, it has never been tested in preterm infants.

This factorial randomised controlled trial will evaluate the effect of increasing amino acid intake (by 1 g/kg/d) and energy intake (by 20 kcal/kg/d) during parenteral nutrition and also of increasing protein intake and energy intake by an extra 1 g/kg/d during enteral nutrition, with and without the stimulation of the infant's physical activity, on growth of extremely low birth weight infants. The investigators aim at demonstrating that increasing energy and protein intake above the standard of care intakes will result in better growth only in association with adequate physical activity, in particular in relation to body composition and lean mass accretion.

Eligibility criteria: Inclusion Criteria:

* 24 weeks \< gestational age \< 32 weeks
* inborn or outborn admitted before 24 hours of age
* parenteral or enteral nutrition start before 48 hours of age
* parental consent

Exclusion Criteria:

* difficulty in starting physical activity stimulation before 10 days of life
* death before 36 W PMA
* diagnosis of necrotising enterocolitis (before 36 W PMA)
* any major surgery (before 36 W PMA)
* congenital syndrome, severe malformations
* inborn errors of metabolism
* parental consent withdrawn

Primary outcomes:
measure: Weight gain (Birth-36 Weeks PMA)
timeFrame: birth up to 36 weeks postmenstrual age
Secondary outcomes:
measure: Muscle ultrasound
timeFrame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d )
measure: Adipose tissue ultrasound
timeFrame: 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d )
measure: Lean body mass estimate using deuterium dilution
timeFrame: 36 weeks postmenstrual age (+-1d )
measure: Skinfold thickness
timeFrame: 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ), between 22 and 24 months (2 years correct age)
measure: Brain MRI
timeFrame: 40 weeks postmenstrual age (+-1d )
measure: Weight
timeFrame: birth, daily up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)
measure: Total body length
timeFrame: birth, weekly until 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)
measure: Head circumference
timeFrame: birth, weekly up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)
measure: Tibial length
timeFrame: birth, 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ), between 22 and 24 months (2 years correct age)
measure: Weight gain (BW recovery-36W PMA)
timeFrame: birth weight recovery up to 36 weeks postmenstrual age
measure: Bayley III Cognitive Score (MDI)
timeFrame: between 22 and 24 months (2 years correct age)
measure: Bayley III Language Score
timeFrame: between 22 and 24 months (2 years correct age)
measure: Bayley III Motor Score (PDI)
timeFrame: between 22 and 24 months (2 years correct age)
measure: Safety (metabolic tolerance)
timeFrame: At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Safety (haematology)
timeFrame: At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Safety (gas-analysis)
timeFrame: At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Bone mineralisation
timeFrame: 6 weeks of age, 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Bone ultrasound (1)
timeFrame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Bone ultrasound (2)
timeFrame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
measure: Measurement of physical activity
timeFrame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ), 40 weeks postmenstrual age (+-1d) if still hospitalized
measure: Morbidity
timeFrame: Hospital stay, on average 36 weeks postmenstrual age
measure: Mortality
timeFrame: hospital stay, on average 36 weeks postmenstrual age
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedale G. Salesi
Study officials:
affiliation: Università Politecnica delle Marche
name: Virgilio P. Carnielli, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellof M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):85-91. doi: 10.1097/MPG.0b013e3181adaee0.
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citation: Bellagamba MP, Carmenati E, D'Ascenzo R, Malatesta M, Spagnoli C, Biagetti C, Burattini I, Carnielli VP. One Extra Gram of Protein to Preterm Infants From Birth to 1800 g: A Single-Blinded Randomized Clinical Trial. J Pediatr Gastroenterol Nutr. 2016 Jun;62(6):879-84. doi: 10.1097/MPG.0000000000000989.
citation: Biolo G, Ciocchi B, Stulle M, Piccoli A, Lorenzon S, Dal Mas V, Barazzoni R, Zanetti M, Guarnieri G. Metabolic consequences of physical inactivity. J Ren Nutr. 2005 Jan;15(1):49-53. doi: 10.1053/j.jrn.2004.09.009.
citation: Schulzke SM, Kaempfen S, Trachsel D, Patole SK. Physical activity programs for promoting bone mineralization and growth in preterm infants. Cochrane Database Syst Rev. 2014 Apr 22;2014(4):CD005387. doi: 10.1002/14651858.CD005387.pub3.
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