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

Dora I A Pereira, Nuredin I Mohammed, Ogochukwu Ofordile, Famalang Camara, Bakary Baldeh, Thomas Mendy, Chilel Sanyang, Amadou T Jallow, Ilias Hossain, James Wason, Andrew M Prentice, Dora I A Pereira, Nuredin I Mohammed, Ogochukwu Ofordile, Famalang Camara, Bakary Baldeh, Thomas Mendy, Chilel Sanyang, Amadou T Jallow, Ilias Hossain, James Wason, Andrew M Prentice

Abstract

Background: 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. Methods: 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 Fe/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 Lactobacillaceae, Bifidobacteriaceae and Enterobacteriaceae. Discussion: 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. Registration: This trial is registered at clinicaltrials.gov ( NCT02941081).

Keywords: IDA; IHAT; anaemia; children; diarrhoea; iron deficiency; iron supplementation; microbiome.

Conflict of interest statement

Competing interests: D.I.A.P. is one of the inventors of the IHAT iron supplementation technology, for which she could receive future awards to inventors through the MRC Awards to Inventor scheme. Notwithstanding, the authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.. Map of Upper River Region…
Figure 1.. Map of Upper River Region in The Gambia, with location of study clinical facilities.
Study samples are collected at one of the clinical facilities, Yorrobawol health center, Darsilami community health post, Konkuba community health post, Taibatu health post and Chamoi Health Center, and transported to the study laboratory in Basse for sample processing and analysis, and from there to other laboratories for further analysis. Map adapted from the Atlas of the Gambia 2004.
Figure 2.. Consort 2010 flow diagram.
Figure 2.. Consort 2010 flow diagram.

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