Hepcidin and Iron in Global Health (HIGH)
| ISRCTN | ISRCTN07210906 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN07210906 |
| Secondary identifying numbers | SCC 1358 Version 1 |
- Submission date
- 19/06/2014
- Registration date
- 16/07/2014
- Last edited
- 16/12/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Haematological Disorders
Plain English summary of protocol
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
Contact information
Scientific
Head of Station, MRC Keneba
MRC International Nutrition Group
MRC Keneba
MRC Unit, The Gambia
Banjul
PO Box 273
Gambia
| rwegmuller@mrc.gm |
Study information
| Study design | Proof-of-concept three-arm double-blind randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study acronym | HIGH |
| Study objectives | 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(s) | The Gambia Government/MRC Joint Ethics Committee, 19/12/2013, ref. SCC 1358v1 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 26/05/2014 |
| Completion date | 30/11/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Lower age limit | 6 Months |
| Upper age limit | 23 Months |
| Sex | Both |
| Target number of participants | 393 |
| Key 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 |
| Key exclusion criteria | 1. Congenital disorders 2. Chronic disease 3. Regular medication 4. Currently participating in another study |
| Date of first enrolment | 26/05/2014 |
| Date of final enrolment | 30/11/2015 |
Locations
Countries of recruitment
- Gambia
Study participating centre
PO Box 273
Gambia
Sponsor information
Research council
c/o Professor Andrew M. Prentice
Director
MRC International Nutrition Group
LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom
| Andrew.Prentice@lshtm.ac.uk | |
"ROR" |
https://ror.org/03x94j517 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 01/09/2016 | Yes | No | |
| Results article | results | 01/12/2016 | Yes | No | |
| Results article | 01/01/2023 | 16/12/2022 | Yes | No |
Editorial Notes
16/12/2022: Publication reference added.
18/11/2016: Publication reference added.
05/09/2016: Publication reference added.
