Iron Babies Pilot Supplementation Trial

Study Overview
=================
Brief Summary
-----------------
2-arm, double blind, placebo controlled, randomised trial, with 50 6-week-old infants per arm randomized to 98 days of daily iron (1.5mg/kg/day as ferrous sulphate) or placebo drops

Detailed Description
-----------------
Healthy infants will be randomised to receive daily supplementation from 6-20wks of either a) iron drops or b) placebo drops. Infants with significant illness or any clinical syndromes that would affect interpretation will be excluded. Low birthweight infants and infants born prematurely will not be excluded. Venous blood samples will be collected at enrollment (age 6 weeks) and after 14 weeks (98 days) of iron/placebo supplementation. Participants will be visited daily in their villages by Fieldworkers (FW) to administer the iron/placebo dose and will interview mothers to complete a short health questionnaire. The iron will be dosed at 75% of WHO guideline dose (ie 1.5mg/kg/day). Weekly, a more detailed morbidity and breastfeeding questionnaires will be administered. Infants will be weighed and measured monthly, along with a faecal sample being taken. During the daily visits, the FWs will record any adverse events (AEs) and ensure the safety of participants. If a child is found unwell or if the mother/guardian reports that the child is unwell, the study nurse will check on the child and decide on treatment/referral to the nearest health centre

Official Title
-----------------
Enhancing Brain Development by Early Iron Supplementation of African Infants: An Enabling Pilot Study

Conditions
-----------------
Iron-deficiency, Anaemia in Early Infancy

Intervention / Treatment
-----------------
* Dietary Supplement: Iron drops/Ferrous sulphate
* Dietary Supplement: Placebo drops


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Infants (male or female) from 6 weeks to 10 weeks of age. Breast fed infants (with plans to continue breastfeeding through 6 months of age). Parent/guardian with participant reside in study site area and are able and willing to adhere to all protocol visits and procedures (willingness to stay in the study area for the 14 weeks of supplementation). Healthy with no current illness and no chronic health problems. Signed or fingerprinted informed consent obtained from participants parent/guardian Exclusion Criteria: Low birthweight babies (ie less than 2.5kg at birth) or babies born prematurely (ie less than 37 weeks) will NOT be excluded. Formula fed infants or those planning to terminate exclusive breast feeding before 6months of age. Acute illness (once acute illness is resolved, if appropriate, as per investigator assessment, participant may be re-revaluated for eligibility) Fever (for eligibility purpose defined as a body temperature greater than 37.5°C or mother report of fever) within 3 days prior to study initiation (once fever/acute illness is resolved, if appropriate, as per investigator assessment, participant may be re-revaluated for eligibility). Administration of any investigational drug within 30 days prior to study initiation or planned administration during the study period. Unwilling to avoid (their child to avoid) the ingestion of supplements or herbal/other traditional medications during the study period. Any history of or evidence for chronic clinically significant (as per investigator assessment) disorder or disease (including, but not limited to, immunodeficiency, autoimmunity, congenital abnormality, bleeding disorder, and pulmonary, cardiovascular, metabolic, neurologic, renal, or hepatic disease). Any history of human immunodeficiency virus, chronic hepatitis B or chronic hepatitis C infections. History of meningitis, seizures, Guillain-Barré syndrome, or other neurological disorders. Any condition that in the opinion of the investigator might compromise the safety or well- being of the participant or compromise adherence to protocol procedures

Ages Eligible for Study
-----------------
Minimum Age: 6 Weeks
Maximum Age: 10 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Daily iron (7.5mg/day as ferrous sulphate) or placebo drops starting from six to ten weeks of age for 98 days. Please note that the daily iron supplement is the intervention product/drug
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iron supplement/ ferrous sulphate syrup<br>administration of daily iron drops, 7.5mg/day iron as ferrous sulphate | Dietary Supplement: Iron drops/Ferrous sulphate<br>* participant will consume daily drops of iron<br>* Other names: Ferrous Sulphate syrup;|
| Placebo Comparator: supplement with placebo<br>administration of daily placebo drops | Dietary Supplement: Placebo drops<br>* Participants will consume daily drops of placebo<br>* Other names: Sorbitol Solution 70%;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum iron level | Serum iron concentration at days 0 and 99 | at day 0 and at day 99 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemoglobin concentration | Haemoglobin concentration at days 0 and 99 | at day 0 and at day 99 | 
| Percentage of infants with anaemia | Percentage of infants with anaemia (defined as: Hb< 110g/L, ) | at day 99 | 
| breast feeding | Duration of breast feeding assessed weekly, up to study day 98. | weekly up to week 14 | 
| maternal reported illnesses | Proportion of maternal-reported illnesses assessed daily up to study day 99. | daily up to day 99 | 
| adverse events assessment | Proportion of adverse events assessed daily, up to study day 99 | daily up to day 99 | 
| Serious adverse events (SAE) assessment | Proportion of serious adverse events assessed daily, up to study day 99 | daily up to day 99 | 
| raised inflammatory markers assessment | Proportion of raised inflammatory markers (CRP/AGP) | after 98 days of supplementation | 
| iron deficiency anemia (Hb < 11 g/dL & sTfR/logFerritin ratio < 2.0 and ferritin < 12 ug/L or < 30 ug/L in the presence of inflammation | Proportion of children that are iron deficiency anaemia (Hb < 11 g/dL & sTfR/logFerritin ratio < 2.0 and ferritin < 12 ug/L or < 30 ug/L in the presence of inflammation) | at day 0 and day 99 | 
| Fecal iron after supplementation | Fecal iron assessed at day 0 and day 99 | day 0 and day 99 | 
| Iron regulation | Hepcidin levels at day 0 and day 99 | day 0 and day 99 | 
| Reticulocytes at day 0 and day 99 | Reticulocytes at day 0 and day 99 | day 0 and day 99 | 
| Erythropoietin at days 0 and 99 | Erythropoietin at days 0 and 99 | day 0 and 99 | 
| Erythroferrone at days 0 and 99 | Erythroferrone at days 0 and 99 | day 0 and 99 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anaemia, infant