Choline and Iron Deficiency

Supplemental Choline to Prevent and Treat Learning and Memory Deficits of Early Iron Deficiency: the SupCHO Study

BACKGROUND:

Iron deficiency limits the neurodevelopmental potential of more than 200 million children each year. Iron therapy is typically started when iron deficiency anemia is first diagnosed after screening for anemia or detection of clinical symptoms of iron deficiency anemia at 12 months of age. But iron started at this time does not fully correct earlier iron-deficiency-mediated brain dysfunction, underscoring the need for low-cost, easily implementable adjunct therapies to iron to treat or prevent this dysfunction in high-risk populations.

GAP Supplementation with the nutrient choline lessens damage to the hippocampus from early-life iron deficiency in pre-clinical models and improves hippocampus-mediated memory in children with Fetal Alcohol Spectrum Disorders. Choline has not been tested in children with iron deficiency anemia, despite strong pre-clinical and clinical evidence supporting a benefit to brain development.

HYPOTHESIS:

Infants with iron deficiency anemia who receive iron and nine months of daily choline supplements will have better scores on specific neurobehavioral tests of recognition memory than infants who receive iron and placebo.

METHODS:

This randomized, double-blinded, placebo-controlled clinical trial will randomize 300 6-month-old infants with iron deficiency anemia at Mulago Hospital, Kampala, Uganda, to iron plus choline or iron plus placebo to test the effect of choline on hippocampus-specific and global neurobehavioral outcomes after nine months.

RESULTS: Pending

IMPACT:

If our hypothesis is correct, choline could be added immediately to standard-of-care treatment for iron deficiency anemia. This intervention could safely mitigate the brain dysfunction of early-life iron deficiency that is often undiagnosed until the hippocampal critical window is closing. This simple, low-cost nutrient could thus have life-long benefit for both individuals and the economic and social prosperity of entire regions.

Study Overview

• Status: Recruiting
• Conditions: Anemia; Pediatric Iron Deficiency
• Intervention / Treatment: Drug: choline bitartrate; Other: placebo drug

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sarah Cusick; Phone Number: 612-723-1694; Email: scusick@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 555455
      • Recruiting
      • University of Minnesota
      • Contact: Sarah Cusick; Phone Number: 612-723-1694; Email: scusick@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 6 months +/- 28 days
• Hb < 11.0 g/dL
• ZPP > = 80
• T<37.5°C
• Malaria-negative based on Rapid Diagnostic Test (RDT)
• Mother is HIV-negative.

Exclusion Criteria:

• Developmental disorder
• Severe malnutrition (severe wasting or bipedal edema)
• Known sickle cell disease
• Neurologic disorder, brain injury, or other condition affecting brain development
• Not currently breastfeeding
• Birthweight < 2000 g

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study group; participants assigned to receive study drug	Drug: choline bitartrate; Daily supplementation for 9 months with 200 mg choline bitartrate
Placebo Comparator: control group; participants assigned to receive placebo drug	Other: placebo drug; Daily supplementation for 9 months with identical placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elicited Imitation score	Elicited Imitation outcomes (number of items correctly recalled and number of steps recalled in the correct order for both immediate and delayed recall) at age 15 months, i.e., after nine months of daily supplementation with choline or placebo.	9 months (1 month = 28 days) after enrollment
1) Composite Score on the Mullen Scales of Early Learning; 2) Behavior Rating Scale (BRS) composite score; 3) Early Childhood Vigilance Test (ECVT, computerized test for attention).	1) Composite Score on the Mullen Scales of Early Learning; 2) Behavior Rating Scale (BRS) composite score; 3) Early Childhood Vigilance Test (ECVT, computerized test for attention).	9 months (1 month = 28 days) after enrollment

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Sarah Cusick, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2025
• Primary Completion (Estimated): September 21, 2027
• Study Completion (Estimated): September 21, 2027

Study Registration Dates

• First Submitted: July 24, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: anemia; iron deficiency; choline
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Iron Metabolism Disorders; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia; Organic Chemicals; Amines; Alcohols; Amino Alcohols; Ethanolamines; Quaternary Ammonium Compounds; Onium Compounds; Trimethyl Ammonium Compounds; Choline
• Other Study ID Numbers: 33410

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No