{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:41:12Z","timestamp":1791819672513,"version":"4.3.4"},"update-to":[{"DOI":"10.12688\/gatesopenres.12866.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000}}],"reference-count":50,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1140952"],"award-info":[{"award-number":["OPP1140952"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK MRC and the UK Department for the International Development (DFID)","award":["MC-A760-5QX00"],"award-info":[{"award-number":["MC-A760-5QX00"]}]}],"content-domain":{"domain":["gatesopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Gates Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:\u00a0<\/ns4:bold>\n                    Iron deficiency and its associated anaemia (IDA) are the leading forms of micronutrient malnutrition worldwide. Here we describe the rationale and design of the first clinical trial evaluating the efficacy and safety of an innovative nano iron supplement, iron hydroxide adipate tartrate (IHAT), for the treatment of IDA in young children (IHAT-GUT trial). Oral iron is often ineffective due to poor absorption and\/or gastrointestinal adverse effects. IHAT is novel since it is effectively absorbed whilst remaining nanoparticulate in the gut, therefore should enable supplementation with fewer symptoms.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    IHAT-GUT is a three-arm, double-blind, randomised, placebo-controlled phase II trial conducted in Gambian children 6-35 months of age. The intervention consists of a 12-week supplementation with either IHAT, ferrous sulphate (both at doses bioequivalent to 12.5 mg\n                    <ns4:sub>Fe<\/ns4:sub>\n                    \/day) or placebo. The trial aims to include 705 children with IDA who will be randomly assigned (1:1:1) to each arm. The primary objectives are to test non-inferiority of IHAT in relation to ferrous sulphate at treating IDA, and to test superiority of IHAT in relation to ferrous sulphate and non-inferiority in relation to placebo in terms of diarrhoea incidence and prevalence. Secondary objectives are mechanistic assessments, to test whether IHAT reduces the burden of enteric pathogens, morbidity, and intestinal inflammation, and that it does not cause detrimental changes to the gut microbiome, particularly in relation to\n                    <ns4:italic>Lactobacillaceae<\/ns4:italic>\n                    ,\n                    <ns4:italic>Bifidobacteriaceae<\/ns4:italic>\n                    and\n                    <ns4:italic>Enterobacteriaceae<\/ns4:italic>\n                    .\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Discussion:<\/ns4:bold>\n                    This trial will test the hypothesis that supplementation with IHAT eliminates iron deficiency and improves haemoglobin levels without inducing gastrointestinal adverse effects. If shown to be the case, this would open the possibility for further testing and use of IHAT as a novel iron source for micronutrient intervention strategies in resource-poor countries, with the ultimate aim to help reduce the IDA global burden.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Registration:<\/ns4:bold>\n                    This trial is registered at clinicaltrials.gov (\n                    <ns4:ext-link xmlns:ns3=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns3:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02941081\">NCT02941081<\/ns4:ext-link>\n                    ).\n                  <\/ns4:p>","DOI":"10.12688\/gatesopenres.12866.2","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T07:50:08Z","timestamp":1539244208000},"page":"48","update-policy":"https:\/\/doi.org\/10.12688\/gatesopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["A novel nano-iron supplement to safely combat iron deficiency and anaemia in young children: The IHAT-GUT double-blind, randomised, placebo-controlled trial protocol"],"prefix":"10.12688","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5688-4448","authenticated-orcid":false,"given":"Dora I.A.","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuredin I.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogochukwu","family":"Ofordile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Famalang","family":"Camara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakary","family":"Baldeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chilel","family":"Sanyang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadou T.","family":"Jallow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilias","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Wason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Prentice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1211-1259","DOI":"10.1016\/S0140-6736(17)32154-2","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 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Guidance for Industry"}],"container-title":["Gates Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T03:30:29Z","timestamp":1720668629000},"score":1,"resource":{"primary":{"URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,11]]},"references-count":50,"URL":"https:\/\/doi.org\/10.12688\/gatesopenres.12866.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/gatesopenres.13967.r26711","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/gatesopenres.13967.r26711","asserted-by":"object"}]},"ISSN":["2572-4754"],"issn-type":[{"value":"2572-4754","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,11]]},"assertion":[{"value":"Indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/gatesopenres.13967.r26711, Toby Richards, Division of Surgery and Interventional Science, University College London, London, UK, 15 Oct 2018, version 2, indexed","URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v2#referee-response-26711","order":0,"name":"referee-response-26711","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/gatesopenres.13950.r26668, Robert C. Hider, Division of Pharmaceutical Science, King\u2019s College London, London, UK, 04 Oct 2018, version 1, 1 approved, 1 approved with reservations","URL":"https:\/\/gatesopenresearch.org\/articles\/2-48\/v1#referee-response-26668","order":1,"name":"referee-response-26668","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study is supported by a Bill & Melinda Gates Foundation Grand Challenges New Interventions in Global Health award [OPP1140952]. The Nutrition Group of the MRC Unit The Gambia at LSHTM are supported by core funding MC-A760-5QX00 to the MRC Unit The Gambia\/MRC International Nutrition Group by the UK MRC and the UK Department for the International Development (DFID) under the MRC\/DFID Concordat agreement. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}