Iron Supplementation and Intestinal Health

NCT04497012 | Unknown Phase 4 DMC FDA Drug

• 1 other identifier: Pro00041470
• Study Type: interventional
• Target: 183
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Anemia of Prematurity; Very Low Birth Weight Infant

Keywords

intestinal dysbiosis

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• Rate of auditory myelination

  up to 36 weeks corrected gestational age

• Level of Iron storage

  at 4 weeks after birth

Study Arms (2)

Low Iron Sulfate Supplementation

ACTIVE COMPARATOR

Participants will be given 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 iron dose until 36 week corrected gestational age or discharge, whichever comes first.

Drug: 2mg/kg/day Iron Sulfate

High Iron Sulfate Supplementation

ACTIVE COMPARATOR

Participants will be given 6 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 iron dose until 36 week corrected gestational age or discharge, whichever comes first.

Drug: 6 mg/kg/day Iron Sulfate

Interventions

2mg/kg/day Iron Sulfate DRUG

Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.

Also known as: Low dose iron supplementation

Low Iron Sulfate Supplementation

6 mg/kg/day Iron Sulfate DRUG

Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.

Also known as: High dose iron supplementation

High Iron Sulfate Supplementation

Eligibility Criteria

• Age: 1 Day - 6 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• \<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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of South Florida: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Tampa General Hospital

Tampa, Florida, 33606, United States

RECRUITING

Related Publications (6)

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

  PMID: 20817366 BACKGROUND

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

  PMID: 22419305 BACKGROUND

• 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. 2010 Dec;92(6):1406-15. doi: 10.3945/ajcn.110.004564. Epub 2010 Oct 20.

  PMID: 20962160 BACKGROUND

• 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 abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015 May;64(5):731-42. doi: 10.1136/gutjnl-2014-307720. Epub 2014 Aug 20.

  PMID: 25143342 BACKGROUND

• 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.

  PMID: 28753958 BACKGROUND

• 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: 10.1016/j.jpeds.2013.01.024. Epub 2013 Feb 26.

  PMID: 23452586 BACKGROUND

MeSH Terms

Conditions

Anemia

Interventions

Iron-Dextran Complex

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Dextrans; Glucans; Polysaccharides; Carbohydrates

Central Study Contacts

Marcia Kneusel

CONTACT

813-844-3395; mkneusel@usf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, care givers, medical teams, investigator, and outcome assessors are blinded from the iron treatment dose for the duration of the study. Only research pharmacists and members of the Data and Safety Monitor Board are unblinded during the study period. In an event when the medical team urgently needs to know the iron dose the participant is receiving for proper clinical management of the subject, the principal investigator or a designee will be notified by cell phone. Their contact information are located in the medical workrooms and the unit pharmacy. The principal investigator or the designee will immediately call the research pharmacy phone to request an emergency unblinding of that particular participant. The principal investigator will inform IRB and the sponsor of the unblinding event within 24 hours.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatologist

Model Details: Randomize subjects to low and high dose iron supplementations

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: August 4, 2020
• Study Start: November 17, 2020
• Primary Completion: March 30, 2025
• Study Completion: July 31, 2025
• Last Updated: January 22, 2025

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)