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High Protein and High Energy Intakes and Physical Activity on Growth of Extremely Low Birth Weight Infants

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ClinicalTrials.gov Identifier: NCT03374033
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : December 15, 2017
Sponsor:
Information provided by (Responsible Party):
Virgilio Paolo Carnielli, Università Politecnica delle Marche

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 .

Condition or disease Intervention/treatment Phase
Infant, Very Low Birth Weight Dietary Supplement: NUTR + Behavioral: STIMUL + Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : April 10, 2017
Estimated Primary Completion Date : April 3, 2020
Estimated Study Completion Date : July 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: NUTR (Nutrition) 0_STIMUL(Stimulation) 0
Standard Nutrition and no Physical Stimulation
Experimental: NUTR 0_STIMUL +
Standard Nutrition and Physical Stimulation
Behavioral: STIMUL +
Physical activity stimulation consists in flexion/extension of the 4 limbs and other motion exercises of the shoulder girdle and of the hips. This stimulation will take place before the feed for a mean of 30 times a week (minimum 24- maximum 36 times a week, 10 minutes each time) and will start within the 10th day of life until 36 weeks postmenstrual age

Experimental: NUTR +_STIMUL 0
Enhanced Nutrition, and no Physical Stimulation
Dietary Supplement: NUTR +
one extra g/kg/d of protein and lipids starting before 48 hours after birth until 36 weeks postmenstrual age

Experimental: NUTR +_STIMUL +
Enhanced Nutrition and Physical Stimulation
Dietary Supplement: NUTR +
one extra g/kg/d of protein and lipids starting before 48 hours after birth until 36 weeks postmenstrual age

Behavioral: STIMUL +
Physical activity stimulation consists in flexion/extension of the 4 limbs and other motion exercises of the shoulder girdle and of the hips. This stimulation will take place before the feed for a mean of 30 times a week (minimum 24- maximum 36 times a week, 10 minutes each time) and will start within the 10th day of life until 36 weeks postmenstrual age




Primary Outcome Measures :
  1. Weight gain (Birth-36 Weeks PMA) [ Time Frame: birth up to 36 weeks postmenstrual age ]
    Weight gain from birth up to 36 weeks postmenstrual age (g/kg/d)


Secondary Outcome Measures :
  1. Muscle ultrasound [ Time Frame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ) ]
    Ultrasound measurement of mid thigh and mid arm muscle thickness (cm)

  2. Adipose tissue ultrasound [ Time Frame: 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ) ]
    Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm)

  3. Lean body mass estimate using deuterium dilution [ Time Frame: 36 weeks postmenstrual age (+-1d ) ]
    Urinary deuterium enrichment after 6 and 12 hours from deuterium oral administration (baseline)

  4. Skinfold thickness [ Time Frame: 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) ]
    Biceps and triceps skinfold thickness (both arms) (cm)

  5. Brain MRI [ Time Frame: 40 weeks postmenstrual age (+-1d ) ]
    Brain injury, growth and maturation according to Kidokoro et al.

  6. Weight [ Time Frame: birth, daily up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) ]
    weight measured by a digital infant scale (g)

  7. Total body length [ Time Frame: birth, weekly until 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) ]
    Total body length measured by a neonatal stadiometer (cm)

  8. Head circumference [ Time Frame: birth, weekly up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) ]
    Head circumference measured by a flexible non-stretchable tape (cm)

  9. Tibial length [ Time Frame: 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) ]
    Knee-heel length measured by knemometry (cm)

  10. Weight gain (BW recovery-36W PMA) [ Time Frame: birth weight recovery up to 36 weeks postmenstrual age ]
    Weight gain from the birth weight recovery until 36 weeks postmenstrual age (g/kg/d)

  11. Bayley III Cognitive Score (MDI) [ Time Frame: between 22 and 24 months (2 years correct age) ]
    Cognitive scale (range 55-145). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development.

  12. Bayley III Language Score [ Time Frame: between 22 and 24 months (2 years correct age) ]
    Language scale (range 45-155). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development.

  13. Bayley III Motor Score (PDI) [ Time Frame: between 22 and 24 months (2 years correct age) ]
    Motor scale (range 45-155). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development.

  14. Safety (metabolic tolerance) [ Time Frame: 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 ) ]
    Plasma and urinary urea (mg/dl), Plasma triglycerides (mg/dl), blood glucose (mg/dl)

  15. Safety (haematology) [ Time Frame: 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 ) ]
    Complete blood count

  16. Safety (gas-analysis) [ Time Frame: 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 ) ]
    Gas-analisys

  17. Bone mineralisation [ Time Frame: 6 weeks of age, 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) ]
    Plasma and urinary calcium and phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin measurements

  18. Bone ultrasound (1) [ Time Frame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) ]
    metacarpus speed of sound (m/s)

  19. Bone ultrasound (2) [ Time Frame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) ]
    Metacarpus bone transmission time (ms)

  20. Measurement of physical activity [ Time Frame: 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ), 40 weeks postmenstrual age (+-1d) if still hospitalized ]
    Different levels of activity are assigned according to the Bruck's activity scale as described by Freymond et al. (24 hour continuous recording using a video camera). Levels of activity are defined as follows: 0, no body, arm, or leg movement, facial movement present or not with eyes closed or open; 1, arm or leg movement with eyes closed or open; 2, total body movement with eyes closed or open; 3, crying. Levels of activity in each group are expressed as percentage of time spent during the day in each level.

  21. Morbidity [ Time Frame: Hospital stay, on average 36 weeks postmenstrual age ]
    incidence of the main complication of prematurity

  22. Mortality [ Time Frame: hospital stay, on average 36 weeks postmenstrual age ]
    incidence of mortality



Information from the National Library of Medicine

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Ages Eligible for Study:   24 Weeks to 32 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374033


Contacts
Contact: Virgilio P. Carnielli, MD, PhD 00390715962045 v.carnielli@univpm.it
Contact: Chiara Biagetti, MD 00390715962014 chiara.biagetti@ospedaliriuniti.marche.it

Locations
Italy
Ospedale G. Salesi Recruiting
Ancona, Italy, 60123
Contact: Virgilio P. Carnielli, MD, PhD    00390715962045    v.carnielli@univpm.it   
Contact: Chiara Biagetti, MD    00390715962014    chiara.biagetti@ospedaliriuniti.marche.it   
Sponsors and Collaborators
Università Politecnica delle Marche
Investigators
Principal Investigator: Virgilio P. Carnielli, MD, PhD Università Politecnica delle Marche

Publications of Results:
Other Publications:

Responsible Party: Virgilio Paolo Carnielli, Head of Neonatology Department, Università Politecnica delle Marche
ClinicalTrials.gov Identifier: NCT03374033     History of Changes
Other Study ID Numbers: DG-297
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: December 15, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Virgilio Paolo Carnielli, Università Politecnica delle Marche:
Preterm infants, growth, nutrition, physical activity

Additional relevant MeSH terms:
Body Weight
Birth Weight
Signs and Symptoms