Iron Supplementation and Intestinal Health

Very Low Birth Weight Infant Clinical Trial

Official title:

Enteral Iron Supplementation and Intestinal Health in Preterm Infants

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04497012
• Other study ID #: Pro00041470
• Status: Recruiting
• Phase: Phase 4
• Start date: November 17, 2020
• Est. completion date: July 31, 2025

Study information

• Verified date: June 2023
• Source: University of South Florida
• Contact: Marcia Kneusel
• Phone: 813-844-3395
• Email: mkneusel[@]usf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized double-blinded study of enteral iron supplementation in Very Low Birth Weight infants. The subjects will be randomized into low dose (2 mg/kg/day) and high dose (6 mg/kg/day) of daily iron supplementation. The primary outcomes are intestinal health including microbiome, inflammation, and barrier function.

Description:

Infants and mothers will be recruited at a single academic level III NICU at Tampa General Hospital, Tampa, FL. Inclusion criteria infants: <1500 g at birth, expected to live beyond 2 weeks, not yet started on oral iron supplementation (OIS), and parental consent. Exclusion criteria infants: congenital intestinal defects, history of intestinal infection or perforation before OIS. Infants who require epogen for religious reason to prevent them from getting blood transfusions will be excluded from the study.

Intervention: Participants will be randomized to either 6 mg/kg/day or 2 mg/kg/day total of elemental iron once a day when they are consuming 150-160 ml/kg/day of enteral feeds and are at least 14 days old. The total iron doses will be provided by fortification of feeds and liquid iron sulfate and will be weight adjusted once a week. The participants will receive the study OIS doses until 36 week corrected gestational age or discharge, whichever comes first.

Sample collection and testing:

1. Stool and urine collection: We will collect weekly stool and urine samples non-invasively starting at enrollment until study completion. Samples will be collected from soiled diapers.

2. Blood tests: We will collect C-reactive protein (CRP) and ferritin level at 4 weeks after birth at the same time as other routine labs (complete blood count, reticulocyte count, and liver function test).

3. Monaural auditory brainstem response (ABR): for each ear will be performed at 36 weeks corrected gestational age or at discharge under the supervision of an audiologist who is blinded to the infants assigned iron doses and test results (stool microbiome, blood and urine tests).

Monitoring: iron supplementation dose will be increased by 2 mg/kg/day if ferritin level <100 mg/dL and the dose will be held if ferritin level >400 mg/dL. Ferritin level will be rechecked every 2 weeks until normalized. Hematocrit and reticulocyte count will be monitored by the medical team.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 183
• Est. completion date: July 31, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 6 Months

Eligibility

Inclusion Criteria:

• <1500 g at birth, expected to live beyond 2 weeks, not yet started on oral iron supplementation (OIS), with mother at least 18 years of age, and parental consent.

Exclusion Criteria:

• congenital intestinal defects, history of intestinal infection or perforation before OIS. Infants who require epogen for religious reason to prevent them from getting blood transfusions will be excluded from the study.

Related Conditions & MeSH terms

• Anemia of Prematurity
• Birth Weight
• Very Low Birth Weight Infant

Intervention

Drug:
• 2mg/kg/day Iron Sulfate
Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.
• 6 mg/kg/day Iron Sulfate
Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.

Locations

Country	Name	City	State
United States	Tampa General Hospital	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of South Florida	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB. Iron fortification adversely affects the gut microbiome, increases pathogen abun — View Citation

Krebs NF, Sherlock LG, Westcott J, Culbertson D, Hambidge KM, Feazel LM, Robertson CE, Frank DN. Effects of different complementary feeding regimens on iron status and enteric microbiota in breastfed infants. J Pediatr. 2013 Aug;163(2):416-23. doi: 10.101 — View Citation

Mills RJ, Davies MW. Enteral iron supplementation in preterm and low birth weight infants. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD005095. doi: 10.1002/14651858.CD005095.pub2. — View Citation

Strauss RG. Anaemia of prematurity: pathophysiology and treatment. Blood Rev. 2010 Nov;24(6):221-5. doi: 10.1016/j.blre.2010.08.001. — View Citation

Tang M, Frank DN, Hendricks AE, Ir D, Esamai F, Liechty E, Hambidge KM, Krebs NF. Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants. Nutrients. 2017 Jul 19;9(7):776. doi: 10.3390/nu9070776. — View Citation

Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in stool bacterial percentages from before to after iron supplementation	Comparing the changes in the median percentages of stool bacteria between the two groups. Change = post-iron (1 week, 2 weeks after iron and at discharge) - pre-iron	from baseline to 1 week and 2 weeks after iron supplementation started
Primary	Change in fecal calprotectin from before to after iron supplementation	Comparing the mean fecal calprotectin levels, an inflammatory stool biomarker, between the two groups. Change = post-iron (1 week, 2 weeks after iron and at discharge) - pre-iron.	from baseline to 1 week and 2 weeks after iron supplementation started
Primary	Change in urine Claudin-3 and I-FABP from before to after iron supplementation	Comparing the mean urine claudin-3 and I-FABP levels, biomarkers for intestinal barrier function, between the two groups. Change = post-iron (1 week, 2 weeks after iron and at discharge) - pre-iron	from baseline to 1 week and 2 weeks after iron supplementation started
Secondary	Rate of auditory myelination	Comparing the mean auditory latency levels between the two groups at 36 weeks corrected gestational age or at discharge.	up to 36 weeks corrected gestational age
Secondary	Level of Iron storage	Comparing the mean Ferritin levels between the two groups at 4 weeks after birth	at 4 weeks after birth