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Iron Supplementation and Intestinal Health

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ClinicalTrials.gov Identifier: NCT04497012
Recruitment Status : Recruiting
First Posted : August 4, 2020
Last Update Posted : June 16, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Thao (Tina) Ho, University of South Florida

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.

Condition or disease Intervention/treatment Phase
Anemia of Prematurity Very Low Birth Weight Infant Drug: 2mg/kg/day Iron Sulfate Drug: 6 mg/kg/day Iron Sulfate Phase 4

Detailed 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 1-2 weeks until normalized. Hematocrit and reticulocyte count will be monitored by the medical team.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 183 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomize subjects to low and high dose iron supplementations
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: Enteral Iron Supplementation and Intestinal Health in Preterm Infants
Actual Study Start Date : November 17, 2020
Estimated Primary Completion Date : November 30, 2024
Estimated Study Completion Date : July 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Birth Weight Iron

Arm Intervention/treatment
Active Comparator: Low Iron Sulfate Supplementation
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
Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.
Other Name: Low dose iron supplementation

Active Comparator: High Iron Sulfate Supplementation
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
Iron Sulfate will be given in liquid form via nasal or oral gastric tube with feeds.
Other Name: High dose iron supplementation




Primary Outcome Measures :
  1. Change in stool bacterial percentages from before to after iron supplementation [ Time Frame: from baseline to 1 week and 2 weeks after iron supplementation started ]
    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

  2. Change in fecal calprotectin from before to after iron supplementation [ Time Frame: from baseline to 1 week and 2 weeks after iron supplementation started ]
    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.

  3. Change in urine Claudin-3 and I-FABP from before to after iron supplementation [ Time Frame: from baseline to 1 week and 2 weeks after iron supplementation started ]
    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


Secondary Outcome Measures :
  1. Rate of auditory myelination [ Time Frame: up to 36 weeks corrected gestational age ]
    Comparing the mean auditory latency levels between the two groups at 36 weeks corrected gestational age or at discharge.

  2. Level of Iron storage [ Time Frame: at 4 weeks after birth ]
    Comparing the mean Ferritin levels between the two groups at 4 weeks after birth



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

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): NCT04497012


Contacts
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Contact: Marcia Kneusel 813-844-3395 mkneusel@usf.edu

Locations
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United States, Florida
Tampa General Hospital Recruiting
Tampa, Florida, United States, 33606
Contact: Marcia Kneusel    813-844-3395      
Sponsors and Collaborators
University of South Florida
National Heart, Lung, and Blood Institute (NHLBI)
Publications of Results:

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Responsible Party: Thao (Tina) Ho, Neonatologist, University of South Florida
ClinicalTrials.gov Identifier: NCT04497012    
Other Study ID Numbers: Pro00041470
First Posted: August 4, 2020    Key Record Dates
Last Update Posted: June 16, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Thao (Tina) Ho, University of South Florida:
intestinal dysbiosis
Additional relevant MeSH terms:
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Birth Weight
Body Weight
Iron
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs