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Iron Deficiency, Anaemia in ChildrenPhase 2IHAT-GutNCT02941081

A Novel Nano-iron Supplement to Safely Combat Iron Deficiency and Anaemia in Young Children: a Doubleblind Randomised Controlled Trial

A Phase 2 study testing IHAT and Ferrous Sulphate in people with Iron Deficiency, Anaemia in Children, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 to 35 monthsHealthy volunteers can take part
Conditions the study is for
Iron Deficiency, Anaemia in Children
What is being tested?
IHAT and Ferrous Sulphate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
645 participants
Where
1 siteThe Gambia
Study dates
8 Jan 2018to 28 May 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 35 months
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Age 6-35 mo.
  • Free of malaria (RDT negative)
  • HAZ, WAZ, WHZ >-3 SD
  • IDA defined as 7≤ Hb <11 g/dl AND ferritin<30 μg/L
  • Resident in the study area (and planning to remain in the study area for the duration of the trial)
  • Ability and willingness to comply with the study protocol (daily intake of supplement and daily study visits with weekly finger prick)
  • Informed consent given by parent or guardian

Who cannot join

  • Congenital disorders
  • Chronic disease
  • Currently participating in another study
  • Currently taking iron supplements/multiple micronutrient supplements
  • Currently experiencing moderate-severe diarrhoea, defined as those diarrhoea episodes where (i) the child passes more than 5 loose or watery stools per day, (ii) there is blood in the stool (dysentery), or (iii) the child shows signs of clinical dehydration (assessed by the study nurse based on physical signs such as little or no urination, sunken eyes, and skin that lacks its normal elasticity), will usually require treatment (including ORS)

Trial locations and contacts

1 site in 1 country.

The Gambia1 site
  • MRC Unit The Gambia

    Basse Santa Su, Upper River Division

Other trials in The Gambia

About this study

Official title: A Novel Nano-iron Supplement (IHAT) to Safely Combat Iron Deficiency and Anaemia (IDA) in Young Children: a Doubleblind Randomised Controlled Trial

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.

Read the 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

Being tested
IHAT, Ferrous Sulphate, Placebo
Keywords
iron supplement
Medical subject headings
Iron Deficiencies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IHATDietary supplement

    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)

  • Ferrous SulphateDietary supplement

    1 dose/day single IMP containing FeSO4 powder equivalent to 12.5 mg Fe

  • PlaceboOther

    1 dose/day containing a placebo powder (no-iron, 'sugar' compound)

Study groups in NCT02941081
Study groupRoleWhat they receive
IHATExperimentalIHAT arm: novel iron supplement - 1 dose/day single IMP containing IHAT (iron hydroxide adipate tartrate) powder bioequivalent to 12.5 mg elemental iron (i.e. 20 mg Fe taking into account IHAT's relative bioavailability to ferrous sulphate)
Receives: Dietary Supplement: IHAT
ferrous sulphateActive comparatorFerrous sulphate arm: clinical standard of oral iron supplementation - 1 dose/day single IMP containing ferrous sulphate (FeSO4 ) powder equivalent to 12.5 mg elemental iron
Receives: Dietary Supplement: Ferrous Sulphate
placeboPlacebo comparatorPlacebo arm: 'no iron' arm - 1 dose/day containing saccharose powder
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. proportion of children with iron deficiency

    Proportion of children at 12 weeks with iron deficiency (Cobas analyser). The choice of the marker to use to define iron deficiency will be made at the time of locking the data analysis plan and we will use the most up to date WHO recommendation at the time. But most likely it will be: ferritin <12 mcg/liter, or <30 mcg/liter in the presence of inflammation (CRP>5), and (soluble transferrin receptor - sTfR)/log10 ferritin index >2.

    Measured: at 12 weeks

  2. Proportion of children with anaemia

    Proportion of children at 12 weeks with anaemia (Medonic analyser). Anaemia is defined as haemoglobin < 11 g/dl.

    Measured: at 12 weeks

  3. incidence density' of moderate-severe diarrhea episodes

    Incidence density of moderate-severe diarrhoea episodes over the 12 weeks (questionnaire/assessment by study nurse). Incidence density is defined as the number of new episodes of moderate-severe diarrhoea per child over the 12 weeks intervention

    Measured: over 12 weeks

  4. period prevalence of moderate-severe diarrhoea

    Period prevalence of moderate-severe diarrhea over the 12 weeks (questionnaire/assessment by study nurse). Period prevalence is defined as the proportion of children with at least one episode of moderate-severe diarrhea over the 12 weeks intervention

    Measured: over 12 weeks

Secondary outcomes (12)
  1. Alpha diversity and beta diversity of the faecal microbiome

    Alpha diversity and beta diversity of the faecal microbiome at baseline, 4 weeks and 12 weeks data from MiSeq sequencing of faecal 16S rRNA)

    Measured: at baseline, 4 weeks and 12 weeks

  2. hospitalisation events

    Number of new hospitalization events per child over the 12 weeks (questionnaire

    Measured: over 12 weeks period

  3. Ratio of enterobacteria/(bifidobacteria+lactobacilli) abundances

    Ratio of enterobacteria/(bifidobacteria+lactobacilli) abundances in the faecal microbiome at baseline, 4 weeks and 12 weeks (data from MiSeq sequencing of faecal 16S rRNA)

    Measured: at baseline, 4 weeks and 12 weeks

  4. Proportion of children with episodes of respiratory tract infections and malaria

    Proportion of children with episodes of respiratory tract infections and malaria over the 12 weeks (questionnaire)

    Measured: over 12 weeks

  5. Proportion of children with enteric pathogens

    Proportion of children with enteric pathogens at baseline, 4 weeks and 12 weeks (targeted qPCR)

    Measured: at baseline, 4 weeks and 12 weeks

  6. Gut inflammation

    Gut inflammation measured with faecal calprotectin (ELISA)

    Measured: baseline day 1, day 15 and day 85

  7. Longitudinal prevalence of moderate-severe diarrhoea

    Longitudinal prevalence of moderate-severe diarrhoea (questionnaire/assessment by study nurse). Longitudinal prevalence is defined as the number of days a child has moderate-severe diarrhea over the 12 weeks intervention

    Measured: over 12 weeks

  8. Incidence density of 'bloody' diarrhea per month

    Incidence density of 'bloody' diarrhea per month (questionnaire/assessment by study nurse). Defined as the number of diarrhea episodes with blood in the stool, as a sign of severe intestinal infection, per child-month of observation

    Measured: per month

  9. Serum C-reactive protein and Alpha-1-acid glycoprotein

    Serum C-reactive protein and Alpha-1-acid glycoprotein (Cobas analyser). Markers of systemic inflammation

    Measured: baseline day 1, day 15 and day 85

  10. Serum hepcidin

    Serum hepcidin (ELISA). Marker of systemic iron handling

    Measured: baseline 1day 1, day 15 and day 85

  11. Serum non-transferrin bound iron

    Serum non-transferrin bound iron (flurescence chemical assay). Marker of systemic iron handling.

    Measured: baseline day 1, day 15 and day 85

  12. Transferrin saturation

    Transferrin saturation (Cobas analyser). Marker of systemic iron handling

    Measured: baseline5day 1, day 14 and day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2016 (estimated)
  2. Study start8 Jan 2018
  3. Primary completion22 Nov 2018
  4. Study completion28 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
645 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02941081
Sponsor's protocol ID
SCC 1489
Acronym
IHAT-Gut
Status last verified
Aug 2019
First submitted
14 Oct 2016
Last updated
14 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Mohammed NI, Wason J, Mendy T, Nass SA, Ofordile O, Camara F, Baldeh B, Sanyang C, Jallow AT, Hossain I, Faria N, Powell JJ, Prentice AM, Pereira DIA. A novel nano-iron supplement versus standard treatment for iron deficiency anaemia in children 6-35 months (IHAT-GUT trial): a double-blind, randomised, placebo-controlled non-inferiority phase II trial in The Gambia. EClinicalMedicine. 2023 Feb 9;56:101853. doi: 10.1016/j.eclinm.2023.101853. eCollection 2023 Feb.

    PubMed 36880049
  • de Goffau MC, Jallow AT, Sanyang C, Prentice AM, Meagher N, Price DJ, Revill PA, Parkhill J, Pereira DIA, Wagner J. Gut microbiomes from Gambian infants reveal the development of a non-industrialized Prevotella-based trophic network. Nat Microbiol. 2022 Jan;7(1):132-144. doi: 10.1038/s41564-021-01023-6. Epub 2021 Dec 31.

    PubMed 34972822
  • Pereira DIA, Mohammed NI, Ofordile O, Camara F, Baldeh B, Mendy T, Sanyang C, Jallow AT, Hossain I, Wason J, Prentice AM. 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. Gates Open Res. 2018 Oct 11;2:48. doi: 10.12688/gatesopenres.12866.2. eCollection 2018.

    PubMed 30569038

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IHAT and Ferrous Sulphate in people with Iron Deficiency, Anaemia in Children, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in The Gambia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

proportion of children with iron deficiency (time frame: at 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02941081, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2019.

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