Plain English Summary
Background and study aims
Iron deficiency anaemia is a medical condition that happens when a lack of iron results in fewer red blood cells being made by the body. Red blood cells carry and store oxygen in the blood and if there are fewer around than normal the organs will not get as much oxygen as usual. This can cause people to become pale and tired, short of breath, have heart palpitations and children may fail to thrive. In low-income (developing) countries, 50% or more of young children suffer from iron deficiency. The World Health Organisation (WHO) has recommended that in countries where more than 40% have anaemia, all young children should be given iron supplements. However, large studies have revealed that giving large doses of iron to young children in areas where there are a high number of infections is risky. Some research suggests that increasing the amount of iron in the body means that more is available to the pathogen as well and this could make the infection worse. Taking this into account, iron supplements should only be given to children when they need it and are best able to use it. However, in areas of high infection, it can be difficult to determine when its best to give a child iron supplements. Hepcidin is a recently discovered hormone that is thought to indicate whether it is safe for someone to take iron. In this study, we hope to find out whether hepcidin can be used to give iron to children more safely.
Who can participate?
Healthy, young children, aged 6-23 months, coming to participating Reproductive and Child Health Clinics (RCH) in Gambia
What does the study involve?
After taking an initial sample of blood and testing it to make sure they are healthy, participants are randomly allocated to one of three groups and take part in the study for 12 weeks. Those in group A (the reference group) are given a micronutrient powder (MNP) containing 12 mg/day iron. Those in group B are given the MNP containing 12 mg/day iron or 0 mg/day iron based on a weekly hepcidin screening to tell if iron should be given for the next 7 days or not. Those in group C are given MNP containing 6 mg/day iron or 0 mg/day iron based on a weekly hepcidin screening to tell if iron should be given for the next 7 days or not. Each week, finger prick blood samples will be taken to find out the hepcidin level, haemoglobin (Hb) level and test for malaria. After the 12 weeks , 2 additional blood samples and 3 stool samples are taken. Morbidity (a measure of how healthy a participant is) is assessed twice a week.
What are the possible benefits and risks of participating?
Benefits will include study participants having access to basic medical services for free. Participants will benefit from daily monitoring by qualified field workers. Anaemia and malaria can also be diagnosed and managed. There are risks associated with a large intake of iron supplements. However, the reference group of this study takes iron as per the recommendation of the World Health Organization and the other two groups take an overall lower dose of iron. If those in group C are moderately anaemic (borderline severe anaemia), they may be at risk of receiving too little iron but will be monitored every week and if seen to become severely anaemic, will be treated as per Gambia Government recommendation for management of severe anaemia. The MNP (MixMe WHO) is distributed by UNICEF and by the World Food Programme and has been used successfully in a number of studies in developing countries. No emergency is expected to result from taking this supplement. However, a nurse will always be available who will decide whether to refer a participant to a health facility in case this is necessary.
Where is the study run from?
This study will be run from 12 communities in Jarra West and Kiang East of Rural Gambia.
When is the study starting and how long is it expected to run for?
May 2014 to November 2015
Who is funding the study?
Medical Research Council (MRC) (UK) and the Bill & Melinda Gates Foundation (USA)
Who is the main contact?
Dr Rita Wegmüller
rwegmuller@mrc.gm
Trial website
Contact information
Type
Scientific
Primary contact
Dr Rita Wegmüller
ORCID ID
Contact details
Head of Station
MRC Keneba
MRC International Nutrition Group
MRC Keneba
MRC Unit
The Gambia
Banjul
PO Box 273
Gambia
-
rwegmuller@mrc.gm
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
SCC 1358 Version 1
Study information
Scientific title
Efficacy and safety of hepcidin-based screen-and-treat approaches using two different doses vs a standard universal approach of iron supplementation in young children in rural Gambia: a double-blind randomized controlled trial
Acronym
HIGH
Study hypothesis
A screen-and-treat approach to iron supplementation in young children will achieve similar efficacy in combating iron deficiency and iron deficiency anaemia at a lower overall dosage of iron which will improve safety and tolerability of iron supplementation.
Ethics approval
The Gambia Government/MRC Joint Ethics Committee, 19/12/2013, ref. SCC 1358v1
Study design
Proof-of-concept three-arm double-blind randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Anaemia
Intervention
The participants will be randomly assigned (1:1:1 ratio) to either receive:
1. MNP containing 12 mg/day iron
2. MNP containing 12 mg/day iron or 0 mg/day iron based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not
3. MNP containing 6 mg/day iron or 0 mg/day iron based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not
Intervention product
The nutritional supplement to be used in this trial is a micronutrient powder (MNP) (MixMe WHO) also distributed by UNICEF and WFP. The MNP contains 15 micronutrients. Three investigational products containing different quantities of iron will be administered:
1. MNP with 12 mg iron
2. MNP with 6 mg iron
3. MNP with 0 mg iron
Intervention type
Supplement
Phase
Drug names
Primary outcome measure
Haemoglobin concentration at study day 84
Secondary outcome measures
1. Proportion of anaemia at study day 84
2. Proportion of iron deficiency at day 84
3. Proportion of iron deficiency anaemia at day 84
4. Iron dosage
5. Morbidity
6. Safety
7. Amount of iron absorbed over the supplementation period
Overall trial start date
26/05/2014
Overall trial end date
30/11/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Apparently healthy
2. Age: 6 to 23 months
3. Not severely malnourished (HAZ, WAZ >-3 SD and WHZ > -2 SD)
4. Hb ≥ 7 g/dL and < 11 g/dL
5. Free of malaria
6. Resident in the study area
7. Ability and willingness to comply with the study protocol (weekly study visits with finger prick blood sampling)
8. Informed consent given by parent or guardian
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
393
Participant exclusion criteria
1. Congenital disorders
2. Chronic disease
3. Regular medication
4. Currently participating in another study
Recruitment start date
26/05/2014
Recruitment end date
30/11/2015
Locations
Countries of recruitment
Gambia
Trial participating centre
MRC Keneba
Banjul
PO Box 273
Gambia
Sponsor information
Organisation
Medical Research Council (MRC) (UK)
Sponsor details
c/o Professor Andrew M. Prentice
Director
MRC International Nutrition Group
LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom
-
Andrew.Prentice@lshtm.ac.uk
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Funder name
Bill and Melinda Gates Foundation
Alternative name(s)
Bill & Melinda Gates Foundation, Gates Foundation, 比尔及梅琳达·盖茨基金会, बिल एंड मिलिंडा गेट्स फाउंडेशन, BMGF, B&MGF
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2016 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/27585745
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27852523