A Novel Nano-iron Supplement to Safely Combat Iron Deficiency and Anaemia in Young Children: a Doubleblind Randomised Controlled Trial
Condition: Iron Deficiency, Anaemia in Children
MeSH terms: Anemia; Anemia, Iron-Deficiency; Iron Deficiencies
Study type: Interventional
Phase: Phase 2

Summary: 
      This study aims to determine whether IHAT is non-inferior to ferrous sulphate at correcting
      iron deficiency and anaemia, and if IHAT does not increase diarrhoea risk in young children
      living in rural and resource-poor areas of the Gambia.

      The study hypothesis is that IHAT will eliminate iron deficiency and improve haemoglobin
      levels in young children without increasing infectious diarrhoea or promoting inflammation in
      the gut.
    

Detailed description: 
      The primary objectives of this trial are: (i) show non-inferiority of IHAT compared to
      ferrous sulphate for efficacy (in terms of Hb and iron deficiency correction); (ii) show
      superiority of IHAT compared to ferrous sulphate in terms of moderate-severe diarrhoea
      (incidence and prevalence); (iii) show non-inferiority of IHAT compared to placebo in terms
      of prevalence of moderate-severe diarrhoea.

      Secondary objectives are: (i) show that IHAT supplementation does not increase enteric
      pathogen burden; (ii) show that IHAT supplementation is non-detrimental to the gut
      microbiome; (iii) show that IHAT supplementation does not cause intestinal inflammation; (iv)
      describe the impact of IHAT supplementation on hospitalisation and morbidity; (v) determine
      the effect of IHAT supplementation on systemic inflammation; (vi) determine the effect of
      IHAT supplementation on systemic markers of iron handling.

      To investigate the primary and secondary objectives the investigators will conduct a 3-arm,
      parallel, randomised, double-blind, placebo-controlled, phase 2, clinical trial.

      Participants will be iron deficient anaemic young children living in rural communities in the
      North Bank of the Upper River Division in The Gambia.

      The communities and health centres within the study catchment area (Wuli and Sandu districts)
      will be sensitised to the study. Young children will be identified using the immunisation
      records at the health centres. At screening, once mothers/guardians of the child have signed
      the informed consent form, the child will be physically examined by a study nurse and, if the
      child is considered as generally healthy, their height and weight will be measured and a
      finger prick blood sample will be collected for Hb and RDT testing. If z-scores are >-3, 7
      ≤Hb< 11 g/dL and the RDT is negative, a small venous blood sample will be collected to
      confirm the Hb levels and determine serum ferritin. A total of 705 eligible children will be
      randomised into the 3 study arms (n=235 per arm).

      In each study arm, the children will be supplemented daily for 12 weeks (84 days) with either
      placebo, ferrous sulphate or IHAT. Blood and stool samples will be collected at baseline (Day
      1) and at day 15 and day 85 during the intervention period. Following the 12 weeks of
      intervention there will be an additional active follow-up period of 4 weeks without
      intervention.

      Highly trained and experienced field workers will be visiting all children every day during
      the 12 weeks supplementation period in order to administer the iron supplements or placebo
      and on these occasions they will check on the children's general health and actively look for
      signs of malaria and co-infections. If a child shows signs of these infections, the field
      worker will refer to the study nurse who will perform adequate tests and the child will be
      offered the appropriate treatment/referral to the next health center. Three times per week,
      morbidity data (including questions regarding fever, diarrhoea, vomiting, cough, any other
      illness, appetite and any mediation taken and assessment of body temperature) will be
      captured. Every week children will be screened using a finger prick blood sample to determine
      their malaria and Hb status and children found with a positive RDT during the study will be
      further tested with a blood film and treated according to national guidelines. These visits
      will continue 4 weeks post intervention to follow-up on AE/SAEs. Any child where Hb falls
      below 7 g/dL during the follow-up study period will stop the study and will be referred to
      the next health centre for managemen
    

Intervention name(s): IHAT; Ferrous Sulphate; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement; Other
Intervention description(s): 1 dose/day single IMP containing IHAT powder bioequivalent to 12.5 mg Fe (i.e. 20 mg Fe taking into account IHAT's relative bioavailability to FeSO4); 1 dose/day single IMP containing FeSO4 powder equivalent to 12.5 mg Fe; 1 dose/day containing a placebo powder (no-iron, 'sugar' compound)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: iron supplement