Supplemental choline to prevent and treat learning and memory deficits of early-life iron deficiency (The SupCHO Study): study protocol for a randomized, placebo-controlled trial in Ugandan infants with iron deficiency anemia.
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| Název: | Supplemental choline to prevent and treat learning and memory deficits of early-life iron deficiency (The SupCHO Study): study protocol for a randomized, placebo-controlled trial in Ugandan infants with iron deficiency anemia. |
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| Autoři: | Cusick SE; Department of Pediatrics, University of Minnesota Medical School, 717 Delaware Street SE Room 359, Minneapolis, MN, 55455, USA. scusick@umn.edu., Mupere E; Department of Paediatrics and Child Health, Makerere University, Mulago Hill Road, PO Box 7072, Kampala, Uganda., Bangirana P; Department of Psychiatry, Makerere University, Mulago Hill Road, PO Box 7072, Kampala, Uganda., Baluku RI; Global Health Uganda, Mawanda Road, Plot 667, PO Box 33842, Kampala, Uganda., Kroupina M; Department of Pediatrics, University of Minnesota Medical School, 2025 E. River Parkway, 7962A, Minneapolis, MN, 55414,, USA., Cheatham CL; Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, 1014 Richard Ave, Kannapolis, NC, 28081, USA., Wozniak JR; Department of Psychiatry and Behavioral Science, University of Minnesota, 2025 E. River Parkway, Minneapolis, MN, 55414, USA., Georgieff MK; Department of Pediatrics, University of Minnesota Medical School, 2450 Riverside Ave S, AO-401, Minneapolis, MN, 55454, USA. |
| Zdroj: | Trials [Trials] 2025 Nov 19; Vol. 26 (1), pp. 524. Date of Electronic Publication: 2025 Nov 19. |
| Způsob vydávání: | Journal Article; Clinical Trial Protocol |
| Jazyk: | English |
| Informace o časopise: | Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BioMed Central, 2006- |
| Výrazy ze slovníku MeSH: | Choline*/administration & dosage , Choline*/adverse effects , Choline*/therapeutic use , Anemia, Iron-Deficiency*/drug therapy , Anemia, Iron-Deficiency*/diagnosis , Anemia, Iron-Deficiency*/psychology , Anemia, Iron-Deficiency*/blood , Anemia, Iron-Deficiency*/complications , Memory Disorders*/prevention & control , Memory Disorders*/etiology , Memory Disorders*/diagnosis , Memory Disorders*/psychology , Memory Disorders*/drug therapy , Dietary Supplements*/adverse effects , Memory*/drug effects , Learning Disabilities*/prevention & control , Learning Disabilities*/etiology , Learning Disabilities*/diagnosis , Learning*/drug effects , Infant Behavior*/drug effects, Humans ; Uganda ; Infant ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Female ; Male ; Hippocampus/drug effects ; Hippocampus/physiopathology ; Age Factors ; Child, Preschool ; Time Factors ; Child Development/drug effects |
| Abstrakt: | Competing Interests: Declarations. Ethics approval and consent to participate {24}: University of Minnesota Institutional Review Board # STUDY00022408 version 1 date 6/18/2024; version 1.1 date 7/2/2025 Mulago Hospital Research Ethics Committee Date # MHREC 2024-158 version 1 5/5/2024; version 1.1 6/24/2025 Uganda National Council of Science and Technology: HS4915ES 11/13/2024 Uganda National Drug Authority: CTA 0288/2025 Written, informed consent to participate will be obtained from the caretakers of all participants. Consent for publication {32}: Attached. Competing interests {28}: The authors declare that they have no competing interests. Background: Iron deficiency (ID) limits the neurodevelopmental potential of more than 200 million children each year. Iron therapy started when IDA is first diagnosed-typically by screening for anemia or detection of clinical symptoms of IDA at 12 months of age-does not fully correct earlier ID-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. Supplementation with the essential nutrient choline lessens damage done to the developing hippocampus when given with iron in pre-clinical rodent models, and choline supplementation improves hippocampus-mediated memory and learning in 2-3-year-old children with Fetal Alcohol Spectrum Disorders, a condition associated with hippocampal damage and one for which ID is a component of the neuropathology. Choline has not been tested in children with IDA. Our overall aim is to conduct a randomized, placebo-controlled clinical trial to test whether nine months of daily choline supplementation along with standard iron therapy improves hippocampus-dependent neurobehavioral outcomes in Ugandan infants with IDA. Methods: Three hundred 6-month-old infants with IDA who present to immunization clinics at Mulago and Kawempe National Referral Hospitals in Kampala, Uganda, will be randomized to iron plus choline or iron plus placebo. Iron (oral ferrous sulfate 2 mg/kg/day) will be given for the first 3 months of follow-up, and a dispersible tablet of choline (200 mg as choline bitartrate) or identical placebo will be given daily for all 9 months of follow-up. We will conduct neurobehavioral tests assessing hippocampus-specific memory and attention and global cognition at enrollment (when each infant is 6 months of age) and after 9 months of follow-up (when each infant is 15 months of age). Discussion: If we find a neurobehavioral benefit when choline is given along with iron, choline could be added immediately to standard of care treatment for IDA. This low-cost intervention could safely mitigate the brain dysfunction of early-life ID that is often not diagnosed until the hippocampal critical window is closing, providing life-long benefit for both the individual and the economic and social prosperity of entire regions. Trial Registration: Clinical trials.gov NCT06527391. Registered on 24 July 2024. (© 2025. The Author(s).) |
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| Grant Information: | E.W. "Al" Thrasher Award Thrasher Research Fund; MIDB Faculty Award University of Minnesota |
| Contributed Indexing: | Keywords: Brain development; Choline; Hippocampus; Iron deficiency; Nutrients and brain |
| Molecular Sequence: | ClinicalTrials.gov NCT06527391 |
| Substance Nomenclature: | N91BDP6H0X (Choline) |
| Entry Date(s): | Date Created: 20251119 Date Completed: 20251119 Latest Revision: 20251121 |
| Update Code: | 20251121 |
| PubMed Central ID: | PMC12628853 |
| DOI: | 10.1186/s13063-025-09246-2 |
| PMID: | 41257751 |
| Databáze: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: Declarations. Ethics approval and consent to participate {24}: University of Minnesota Institutional Review Board # STUDY00022408 version 1 date 6/18/2024; version 1.1 date 7/2/2025 Mulago Hospital Research Ethics Committee Date # MHREC 2024-158 version 1 5/5/2024; version 1.1 6/24/2025 Uganda National Council of Science and Technology: HS4915ES 11/13/2024 Uganda National Drug Authority: CTA 0288/2025 Written, informed consent to participate will be obtained from the caretakers of all participants. Consent for publication {32}: Attached. Competing interests {28}: The authors declare that they have no competing interests.<br />Background: Iron deficiency (ID) limits the neurodevelopmental potential of more than 200 million children each year. Iron therapy started when IDA is first diagnosed-typically by screening for anemia or detection of clinical symptoms of IDA at 12 months of age-does not fully correct earlier ID-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. Supplementation with the essential nutrient choline lessens damage done to the developing hippocampus when given with iron in pre-clinical rodent models, and choline supplementation improves hippocampus-mediated memory and learning in 2-3-year-old children with Fetal Alcohol Spectrum Disorders, a condition associated with hippocampal damage and one for which ID is a component of the neuropathology. Choline has not been tested in children with IDA. Our overall aim is to conduct a randomized, placebo-controlled clinical trial to test whether nine months of daily choline supplementation along with standard iron therapy improves hippocampus-dependent neurobehavioral outcomes in Ugandan infants with IDA.<br />Methods: Three hundred 6-month-old infants with IDA who present to immunization clinics at Mulago and Kawempe National Referral Hospitals in Kampala, Uganda, will be randomized to iron plus choline or iron plus placebo. Iron (oral ferrous sulfate 2 mg/kg/day) will be given for the first 3 months of follow-up, and a dispersible tablet of choline (200 mg as choline bitartrate) or identical placebo will be given daily for all 9 months of follow-up. We will conduct neurobehavioral tests assessing hippocampus-specific memory and attention and global cognition at enrollment (when each infant is 6 months of age) and after 9 months of follow-up (when each infant is 15 months of age).<br />Discussion: If we find a neurobehavioral benefit when choline is given along with iron, choline could be added immediately to standard of care treatment for IDA. This low-cost intervention could safely mitigate the brain dysfunction of early-life ID that is often not diagnosed until the hippocampal critical window is closing, providing life-long benefit for both the individual and the economic and social prosperity of entire regions.<br />Trial Registration: Clinical trials.gov NCT06527391. Registered on 24 July 2024.<br /> (© 2025. The Author(s).) |
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| ISSN: | 1745-6215 |
| DOI: | 10.1186/s13063-025-09246-2 |