Enteral Zinc to Improve Growth in Infants at Risk for Bronchopulmonary Dysplasia

NCT03532555 | Terminated

• 1 other identifier: 102434
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

Multiple factors contribute to growth failure in infants with BPD, including poor nutrient stores, inadequate intake, increased losses, and increased needs. Furthermore, compared to infants without BPD, those with BPD have increased resting metabolic rates and energy expenditure. Growth deficits manifest as lower weight, length, and head circumference, as well as changes in body composition. These deficits precede the development of BPD and persist post-discharge. While similar rates of growth are observed in very low birth weight infants with and without BPD once receiving equal calories, catch up growth does not occur in the BPD group. Thus, early growth deficits remained uncompensated. After iron, zinc is the most metabolically active trace element in the human body. It has a critical role in growth, through its actions on growth hormone, IGF-1, IGFBP-3, and bone metabolism. Prematurity is a risk factor for zinc deficiency, as 60% of zinc accretion occurs in the third trimester. Impaired intake and absorption or excess excretion can further increase this risk. Finally, periods of rapid growth, as seen in preterm infants, increase the need for zinc. Biochemically, zinc deficiency is defined by a serum zinc level less than 55mcg/dl. However, while zinc depletion is associated with deficiency, the opposite may not be true. For example, in starving patients, clinical symptoms of zinc deficiency occur during re-feeding, suggesting overall requirements are related to needs, regardless of overall zinc status. This may be the case in preterm infants, who may have a subclinical deficiency despite serum zinc level. Thus, zinc deficiency should be considered in infants with poor growth despite receiving adequate protein and calories. The objective of this study is to determine whether enteral zinc supplementation leads to improved growth in infants at risk for bronchopulmonary dysplasia (BPD). The investigator's hypothesis is that enteral zinc supplementation in very preterm infants at high risk for BPD will significantly improve growth compared to standard of care.

Conditions

Infant,Premature; Bronchopulmonary Dysplasia; Growth Failure

Keywords

zinc

Outcome Measures

Primary Outcomes (6)

• Growth rate for weight (g/kg/day) from birth to 36+0 weeks corrected gestational age (CGA)

  Average daily changes in weight from birth to 36+0 CGA will be calculated and compared between both arms.

  Birth to 36+0 weeks corrected gestational age

• Growth rate for weight (g/kg/day) from birth to 40+0 weeks CGA

  Average daily changes in weight from birth to 40+0 CGA (or discharge, whichever happens first) will be calculated and compared between both arms.

  Birth to 40+0 weeks corrected gestational age

• Growth rate for length (cm/week) from birth to 36+0 weeks CGA

  Average weekly changes in length from birth to 36+0 weeks CGA will be calculated and compared between both arms.

  Birth to 36+0 weeks corrected gestational age

• Growth rate for length (cm/week) from birth to 40+0 weeks CGA

  Average weekly changes in length from birth to 40+0 weeks (or discharge, whichever happens first) CGA will be calculated and compared between both arms.

  Birth to 40+0 weeks corrected gestational age

• Growth rate for head circumference (cm/week) from birth to 36+0 weeks CGA

  Average weekly changes in head circumference from birth to 36+0 weeks CGA will be calculated and compared between both arms.

  Birth to 36+0 weeks corrected gestational age

• Growth rate for head circumference (cm/week) from birth to 40+0 weeks CGA

  Average weekly changes in head circumference from birth to 40+0 weeks CGA (or discharge, whichever happens first) will be calculated and compared between both arms.

  Birth to 40+0 weeks corrected gestational age

Secondary Outcomes (4)

• Measure changes in serum insulin-like growth factor 1 (IGF-1)

  Study day 0 to 36 weeks corrected gestational age

• Measure changes in serum insulin-like growth factor binding protein 3 (IGFBP-3)

  Study day 0 to 36 weeks corrected gestational age

• Measure rates of severe BPD diagnoses at 36+0 weeks CGA

  36+0 weeks corrected gestational age

• Measure changes in bone quality per tibial ultrasound

  Study day 0 to 36 weeks corrected gestational age

Study Arms (2)

Zinc plus standard of care

ACTIVE COMPARATOR

Infants will receive daily doses of zinc at 2mg/kg from enrollment through 35 6/7 weeks corrected gestational age.

Dietary Supplement: Zinc Acetate

Standard of care only

PLACEBO COMPARATOR

Infants will not receive any doses of zinc through 35 6/7 weeks corrected gestational age

Other: No supplemental zinc

Interventions

Zinc Acetate DIETARY_SUPPLEMENT

Zinc Acetate given with elemental zinc dose of 2mg/kg given orally only daily through 35 6/7 weeks corrected gestational age

Zinc plus standard of care

No supplemental zinc OTHER

Infants will receive standard of care, which is currently no supplemental zinc

Standard of care only

Eligibility Criteria

• Age: 14 Days - 28 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• /7 to 29 6/7 weeks GA
• Birth weight 501 to 1000g, inclusive
• to 28 days of life, inclusive
• day BPD risk score ≥ 50% for death or moderate-severe BPD, calculated using the algorithm on the Neonatal Research Network website (https://neonatal.rti.org/index.cfm?fuseaction=BPDCalculator.start).-

You may not qualify if:

• Major congenital and/or chromosomal anomalies
• Inability to reach 80ml/kg/day enteral feeds by 28 days of life

Sponsors & Collaborators

• University of Utah: lead
• Intermountain Research and Medical Foundation: collaborator

Study Sites (2)

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Utah Health

Salt Lake City, Utah, 84112, United States

Location

Related Publications (2)

• Staub E, Evers K, Askie LM. Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates. Cochrane Database Syst Rev. 2021 Mar 12;3(3):CD012797. doi: 10.1002/14651858.CD012797.pub2.

  PMID: 33710626 DERIVED

• Vazquez-Gomis R, Bosch-Gimenez V, Juste-Ruiz M, Vazquez-Gomis C, Izquierdo-Fos I, Pastor-Rosado J. Zinc concentration in preterm newborns at term age, a prospective observational study. BMJ Paediatr Open. 2019 Sep 13;3(1):e000527. doi: 10.1136/bmjpo-2019-000527. eCollection 2019.

  PMID: 31646195 DERIVED

MeSH Terms

Conditions

Premature Birth; Bronchopulmonary Dysplasia; Failure to Thrive

Interventions

Zinc Acetate

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetic Acid; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Bradley Yoder, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Infants will be stratified by gestational age (23-24 wks, 25-26 wks, 27-29 wks) and then are randomized to receive supplemental oral zinc acetate or no zinc acetate.

Study Record Dates

• First Submitted: April 24, 2018
• First Posted: May 22, 2018
• Study Start: March 22, 2018
• Primary Completion: May 25, 2022
• Study Completion: August 25, 2022
• Last Updated: May 9, 2023

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)