Optimizing Benefits While Reducing Risks of Iron in Malaria-endemic Areas

NCT03897673 | Completed

• 1 other identifier: STUDY00001235
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Daily iron (ferrous sulfate, 2 mg/kg/day) or placebo syrup for first four months (112 days) of the 12-month (336-day) study. Children in the immediate iron group will receive iron syrup for the first three months (84 days) and placebo syrup for the fourth month. Children in the delayed iron group will receive placebo syrup for the first month (28 days) and iron syrup for the second, third, and fourth months.

Conditions

Iron Deficiency Anemia; Iron-deficiency; Anemia, Iron Deficiency; Anemia; Anemia in Children; Malaria

Outcome Measures

Primary Outcomes (4)

• Prevalence of iron deficiency

  Number of participants who are iron deficient (defined as a zinc protoporphyrin (ZPP) concentration greater than or equal to 80 umol/mol heme) at 6-months follow-up in the early iron vs. delayed iron treatment groups

  6-months

• All-cause incidence of infectious illness

  Number of participants who report an infection and total number of infections reported to a study medical officer in the early iron vs. delayed iron treatment groups. This includes all infectious illness including clinical malaria episodes.

  6-months

• Effect on neurobehavioral development: BRS

  Behavior Rating Scales (BRS) scores at 12 months follow up in the early iron vs. delayed iron treatment groups. BRS assesses socioemotional behavior. Scores range from 1-5. Higher raw scores for Fearful/Wary Affect, Negative Affect, and Hyperactivity/Over-activity indicate less optimal behavior, as do lower raw scores for Positive Affect, Adaptation to Change, Exploration and Activity Level.

  12-months

• Effect on neurobehavioral development: MSEL

  Mullen Scales of Early Learning (MSEL) scores at 12 months follow up in the early iron vs. delayed iron treatment groups.The MSEL assesses motor, visual, and language ability and is used to measure cognitive ability. Scores from fine motor, visual reception, receptive language, and expressive language scales are summed to give the early learning composite score, a measure of overall cognitive ability. Each sub-scale is standardized to calculate a standard score, percentile, and age-equivalent score. Composite scores range from 0 to 100 with 100 indicating greater cognitive ability.

  12-months

Secondary Outcomes (10)

• ZPP

  12-months

• Iron status: Hemoglobin

  6- and 12-months

• Iron status: ferritin

  6- and 12-months

• Iron status: soluble transferrin receptor (sTFR)

  6- and 12-months

• Iron status: hepcidin

  6- and 12-months

Study Arms (3)

Early Iron

EXPERIMENTAL

Children in the immediate iron group will receive iron syrup for the first three months (84 days) and placebo syrup for the fourth month.

Dietary Supplement: Early Iron

Delayed Iron

EXPERIMENTAL

Children in the delayed iron group will receive placebo syrup for the first month (28 days) and iron syrup for the second, third, and fourth months.

Dietary Supplement: Delayed Iron

Community Control Children

NO INTERVENTION

Healthy, non-anemic community children will be enrolled from the same households and villages as the children with malaria. They will not have ZPP tested or receive iron, but they will also be under the same illness surveillance as the children with malaria.

Interventions

Early Iron DIETARY_SUPPLEMENT

iron syrup for the first three months (84 days) and placebo syrup for the fourth month

Early Iron

Delayed Iron DIETARY_SUPPLEMENT

placebo syrup for the first month (28 days) and iron syrup for the second, third, and fourth months

Delayed Iron

Eligibility Criteria

• Age: 6 Months - 48 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Hemoglobin 7.0 - 9.9 g/dL
• ZPP \> = 80 µmol/mol heme
• P. falciparum positive by Giemsa smear or RDT positive
• Temperature ≥ 37.5C or history of fever in past 24 hours

You may not qualify if:

• Any WHO criterion for severe malaria, including severe anemia, prostration, cerebral malaria, repeated seizures or symptoms like persistent vomiting, high temperature (\>39.5°C), or tea-colored urine
• Severe malnutrition, as evidenced by severe wasting or bilateral pitting edema
• Known sickle cell disease
• Acute hemorrhage
• Known cancer or leukemia
• Caregiver does not understand English or Luganda
• Same neighborhood, extended household or nearby neighborhood of a child with malaria
• Same age group as a child with malaria
• Hemoglobin \> = 10.0 g/dL
• Clinical malaria infection or any active illness within the past 4 weeks requiring medical care
• Chronic illness requiring medical care
• Major medical abnormalities on screening history or physical exam, including measured temperature ≥ 37.5°C
• Known developmental delay or neurologic disorder
• Prior history of coma
• Caregiver does not understand English or Luganda

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

Kampala, Uganda

Kampala, Uganda

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Anemia; Malaria

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: April 1, 2019
• Study Start: September 1, 2019
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)