AnemiaNCT04097639
Inflammation, Iron Deficiency and Anaemia Study 1
An observational study of Anemia, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
Investigator have previously shown that hepcidin is up-regulated even by low levels of inflammation and, according to our prior stable isotope studies, is predicted to block iron absorption. Read more about this study
- Who is it for?
- Ages 6 to 24 monthsHealthy volunteers can take part
- Conditions the study is for
- Anemia
- How many people
- 120 participants
- Where
- 1 siteThe Gambia
- Study dates
- 7 May 2019to Nov 2021
- Phase
- Observational
- 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 24 months
- All sexes
- Healthy volunteers accepted
- Child
Study population: The study population is young children to who's mothers/guardians the study protocol will be explained orally in the presence of a witness in case they are illiterate or in writing and we will not start any study specific procedure before informed consent is obtained
Who may be able to join
- 1)Male or female children ages 6-8 months at the time of study enrolment.
- 2)Signed or fingerprinted or personally marked written informed consent obtained from their parent/guardian.
- 3)Parent/guardian plans for subject to reside in study site area and are able and willing to adhere to all protocol visits and procedures.
Who cannot join
- 1) Acute illness
- 2) Fever (for eligibility purpose defined as a body temperature greater than 37.5°C) if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility).
- 3)Vaccination less than 7 days prior to study enrollment.
- 4)Administration of immunosuppressants or other immune-modifying agents within 90 days prior to study IP administration (e.g., systemic corticosteroids at doses equivalent to ≥ 0.5 mg/kg/day of prednisone for more than 14 days; topical steroids including inhaled and intranasal steroids are not exclusionary).
- 5)Administration of systemic antibiotic treatment within 3 days prior to study enrolment.
- 6)Any history of or evidence for chronic clinically significant (as per investigator assessment) disorder or disease (including, but not limited to, immunodeficiency, autoimmunity, malnutrition*, congenital abnormality, bleeding disorder, and pulmonary, cardiovascular, metabolic, neurologic, renal, or hepatic disease).
Show all 9Show fewer
- 7)Any history of maternal human immunodeficiency virus, chronic hepatitis B or chronic hepatitis C infections.
- 8)Any condition that in the opinion of the investigator might compromise the safety or well-being of the subject or compromise adherence to protocol procedures.
- 9)Participation in another MRC study.
Trial locations and contacts
1 site in 1 country.
The Gambia1 site, 1 recruiting
- Recruiting
Keneba Field Station
Keneba
Carla Cerami, MD, +2207875756, ccerami@mrc.gm
Elizabeth Ledger, MD, +2202980631, eledger@mrc.gm
About this study
Official title: An Observational Study Designed to Elucidate the Pathways by Which Low-grade Inflammation Contributes to Anaemia in Rural African Children From 6 Months to 2 Years of Age
Investigator have previously shown that hepcidin is up-regulated even by low levels of inflammation and, according to our prior stable isotope studies, is predicted to block iron absorption. In this follow-up observational study, investigator aim to elucidate the potential drivers of this low-grade inflammation and to recalibrate the relationship between hepcidin and iron absorption using a more direct measure of absorption than the stable isotope method which measures the net of absorption and utilization. Investigator will study 120 ostensibly well children (6-24m) living in the rural region of West Kiang.
Investigator will:
- Use detailed clinical screening for possible origins of the low grade inflammation.
- Assess iron absorption and its relationship to iron and anaemia status, inflammation, EPO, erythroferrone and hepcidin.
Read the detailed description
Aim 1:
Hypothesis 1: 'Minor' but persistent infections of the respiratory tract, skin, mouth, and gut cause chronic elevation of hepcidin levels and other markers of infection including CRP.
Research Question 1: What is the relationship between each of the following: CRP, hepcidin, clinical score of skin infections; clinical score of oral health; clinical score of respiratory infections; and systemic markers of gut damage and bacterial translocation (serum EndoCAB and iFABP) and stool markers of inflammation (calprotectin, REG1b and lipocalin2).
Hypothesis 2: Respiratory infections and airway inflammation are the most common cause of low grade inflammation.
Research Question 2: What is the most common source(s) of persistent low-grade inflammation in apparently well children living in rural Gambia.
Aim 2:
Hypothesis: Hepcidin levels above 5.5ng/ml block oral iron absorption.
Research Question: What is the relationship between hepcidin and oral iron absorption in well children living in rural Gambia?
Aim 3:
Hypothesis: Anaemic children with low-grade inflammation have anaemia of inflammation with concomitant iron deficiency that results in inappropriately low levels of EPO production and reticulocytosis for their erythroid mass (Hb levels) levels.
Research Question: Is there decreased EPO synthesis and/or increased EPO resistance in anaemic children with low-grade inflammation living in rural Gambia?
Aim 4:
Hypothesis: First investigator will conduct a hypothesis-free exploratory analysis to assess whether erythroferrone behaves as predicted based upon mouse models (ie up-regulated by stress erythropoiesis and inversely related to hepcidin). Investigator additionally hypothesize that there may be a vicious cycle initiated by inflammation and then perpetuated by the consequent low levels of (iron-restricted) erythropoiesis, leading to low erythroferrone and loss of hepcidin suppression.
Research Question: What is the relationship between erythroferrone, iron status, inflammation, hepcidin, EPO in anaemic and non-anaemic children with and without low-grade inflammation living in rural Gambia? Primary: To examine in detail the pathways by which low-grade inflammation causes iron deficiency anaemia in African children.
Secondary: To assess if anaemia of inflammation and resistance to erythropoietin play a role in causing and perpetuating anaemia in children living in rural Africa.
This is an observational study of 120 children who will be recruited at the routine vaccination clinics or pre-scheduled well-child check-ups at the Keneba clinic. Each child will be seen three times (at 6, 12 and 18 months) and the same protocol will be used at each visit.
Figure 1: Study design At each visit, children will be examined by the Research Clinician or PI using pre-determined validated checklists for possible sources of low-grade inflammation. Each participant will be given a clinical score for skin conditions, oral health, and respiratory infections/airway disease.
After the clinical examination, an oral iron absorption protocol will be initiated:
Step 1: A venous blood sample will be collected and assayed for full blood count (including reticulocyte count) and serum iron markers, hepcidin, erythropoietin (EPO), erythroferrone, IL-6 and EndoCab; Step 2: Children will be given an oral dose of liquid ferrous fumarate at 2mg/kg; Step 3: Between 3-4 hours later a venous blood sample will be drawn for measurement serum iron markers. The change in serum iron levels (measured before and after dosing) will be used as a direct measurement of iron absorption.
- Conditions
- Anemia
- Keywords
- low-grade inflammation, anemia, erythroferrone
- Medical subject headings
- Anemia
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum hepcidin level
To examine in detail the pathways by which low-grade inflammation causes iron deficiency anaemia in African children
Measured: 18 months
clinical score of site and severity of infection and inflammation
Clinical score of skin infections, oral health, eye infections, upper and lower respiratory tract infections. see score below:
Clinical score of inflammation and infection Total out of 81 Range 0-81 0= no inflammation/ infection 81= severe multi focal inflammation/infection
Measured: 18 months
Secondary outcomes (15)
iron absorption
Markers of oral iron absorption - Serum iron concentration
Measured: 18 months
Iron biomarkers - serum ferritin concentration
Measured: 18 months
haematology parameters
Haematology parameters - haemoglobin concentration
Measured: 18 months
inflammatory markers
Inflammatory markers in serum (C-reactive protein, AGP)
Measured: 18 months
Stool parameters - parasites concentration
Measured: 18 months
total iron binding capacity
Measured: 18 months
serum transferrin concentration
Measured: 18 months
soluble transferrin receptor (sTfR)
Measured: 18 months
erythropoietin concentration
Measured: 18 months
erythroferrone concentration
Measured: 18 months
haematology parameters
red blood cell indices measured from full blood count
Measured: 18 months
concentration of helminths in stool
Measured: 18 months
calprotectin
measure of inflammation
Measured: 18 months
Reg1b
measure of inflammation
Measured: 18 months
lipocalin 2
measure of inflammation
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start7 May 2019
- Primary completionDec 2020 (estimated)
- Study completionNov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Sponsor
- Investigators
- Carla Cerami, MD, Principal investigator, Medical Research Council Unit at LSHTM
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097639
- Sponsor's protocol ID
- SCC 1664
- Status last verified
- Jan 2020
- First submitted
- 3 May 2019
- Last updated
- 9 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Study Designed to Elucidate the Pathways by Which Low-grade Inflammation Contributes to Anaemia in Rural African Children From 6 Months to 2 Years of Age
- ClinicalTrials.gov ID
- NCT04097639
- Acronym / sponsor ID
- SCC 1664
- Conditions
- Anemia
- Keywords
- low-grade inflammation, anemia, erythroferrone
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 7 May 2019 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Nov 2021 (estimated)
- First posted
- 20 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigator have previously shown that hepcidin is up-regulated even by low levels of inflammation and, according to our prior stable isotope studies, is predicted to block iron absorption. In this follow-up observational study, investigator aim to elucidate the potential drivers of this low-grade inflammation and to recalibrate the relationship between hepcidin and iron absorption using a more direct measure of absorption than the stable isotope method which measures the net of absorption and utilization. Investigator will study 120 ostensibly well children (6-24m) living in the rural region of West Kiang.
Investigator will:
- Use detailed clinical screening for possible origins of the low grade inflammation.
- Assess iron absorption and its relationship to iron and anaemia status, inflammation, EPO, erythroferrone and hepcidin.
Detailed description
Aim 1:
Hypothesis 1: 'Minor' but persistent infections of the respiratory tract, skin, mouth, and gut cause chronic elevation of hepcidin levels and other markers of infection including CRP.
Research Question 1: What is the relationship between each of the following: CRP, hepcidin, clinical score of skin infections; clinical score of oral health; clinical score of respiratory infections; and systemic markers of gut damage and bacterial translocation (serum EndoCAB and iFABP) and stool markers of inflammation (calprotectin, REG1b and lipocalin2).
Hypothesis 2: Respiratory infections and airway inflammation are the most common cause of low grade inflammation.
Research Question 2: What is the most common source(s) of persistent low-grade inflammation in apparently well children living in rural Gambia.
Aim 2:
Hypothesis: Hepcidin levels above 5.5ng/ml block oral iron absorption.
Research Question: What is the relationship between hepcidin and oral iron absorption in well children living in rural Gambia?
Aim 3:
Hypothesis: Anaemic children with low-grade inflammation have anaemia of inflammation with concomitant iron deficiency that results in inappropriately low levels of EPO production and reticulocytosis for their erythroid mass (Hb levels) levels.
Research Question: Is there decreased EPO synthesis and/or increased EPO resistance in anaemic children with low-grade inflammation living in rural Gambia?
Aim 4:
Hypothesis: First investigator will conduct a hypothesis-free exploratory analysis to assess whether erythroferrone behaves as predicted based upon mouse models (ie up-regulated by stress erythropoiesis and inversely related to hepcidin). Investigator additionally hypothesize that there may be a vicious cycle initiated by inflammation and then perpetuated by the consequent low levels of (iron-restricted) erythropoiesis, leading to low erythroferrone and loss of hepcidin suppression.
Research Question: What is the relationship between erythroferrone, iron status, inflammation, hepcidin, EPO in anaemic and non-anaemic children with and without low-grade inflammation living in rural Gambia? Primary: To examine in detail the pathways by which low-grade inflammation causes iron deficiency anaemia in African children.
Secondary: To assess if anaemia of inflammation and resistance to erythropoietin play a role in causing and perpetuating anaemia in children living in rural Africa.
This is an observational study of 120 children who will be recruited at the routine vaccination clinics or pre-scheduled well-child check-ups at the Keneba clinic. Each child will be seen three times (at 6, 12 and 18 months) and the same protocol will be used at each visit.
Figure 1: Study design At each visit, children will be examined by the Research Clinician or PI using pre-determined validated checklists for possible sources of low-grade inflammation. Each participant will be given a clinical score for skin conditions, oral health, and respiratory infections/airway disease.
After the clinical examination, an oral iron absorption protocol will be initiated:
Step 1: A venous blood sample will be collected and assayed for full blood count (including reticulocyte count) and serum iron markers, hepcidin, erythropoietin (EPO), erythroferrone, IL-6 and EndoCab; Step 2: Children will be given an oral dose of liquid ferrous fumarate at 2mg/kg; Step 3: Between 3-4 hours later a venous blood sample will be drawn for measurement serum iron markers. The change in serum iron levels (measured before and after dosing) will be used as a direct measurement of iron absorption.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 6 to 24 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- The study population is young children to who's mothers/guardians the study protocol will be explained orally in the presence of a witness in case they are illiterate or in writing and we will not start any study specific procedure before informed consent is obtained
Key inclusion criteria (3 listed)
- 1)Male or female children ages 6-8 months at the time of study enrolment.
- 2)Signed or fingerprinted or personally marked written informed consent obtained from their parent/guardian.
- 3)Parent/guardian plans for subject to reside in study site area and are able and willing to adhere to all protocol visits and procedures.
Key exclusion criteria (9 listed)
- 1) Acute illness
- 2) Fever (for eligibility purpose defined as a body temperature greater than 37.5°C) if appropriate, as per investigator assessment, subject may be re-revaluated for eligibility).
- 3)Vaccination less than 7 days prior to study enrollment.
- 4)Administration of immunosuppressants or other immune-modifying agents within 90 days prior to study IP administration (e.g., systemic corticosteroids at doses equivalent to ≥ 0.5 mg/kg/day of prednisone for more than 14 days; topical steroids including inhaled and intranasal steroids are not exclusionary).
- 5)Administration of systemic antibiotic treatment within 3 days prior to study enrolment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Serum hepcidin level
Time frame: 18 months
To examine in detail the pathways by which low-grade inflammation causes iron deficiency anaemia in African children
clinical score of site and severity of infection and inflammation
Time frame: 18 months
Clinical score of skin infections, oral health, eye infections, upper and lower respiratory tract infections. see score below: Clinical score of inflammation and infection Total out of 81 Range 0-81 0= no inflammation/ infection 81= severe multi focal inflammation/infection
15 secondary outcomes
iron absorption
Time frame: 18 months
Iron biomarkers - serum ferritin concentration
Time frame: 18 months
haematology parameters
Time frame: 18 months
inflammatory markers
Time frame: 18 months
Stool parameters - parasites concentration
Time frame: 18 months
total iron binding capacity
Time frame: 18 months
serum transferrin concentration
Time frame: 18 months
soluble transferrin receptor (sTfR)
Time frame: 18 months
erythropoietin concentration
Time frame: 18 months
erythroferrone concentration
Time frame: 18 months
haematology parameters
Time frame: 18 months
concentration of helminths in stool
Time frame: 18 months
calprotectin
Time frame: 18 months
Reg1b
Time frame: 18 months
lipocalin 2
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carla Cerami, MD principal investigator
Medical Research Council Unit at LSHTM
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anemia, 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 3 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 9 Jan 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Carla Cerami, MD (+2207875756, ccerami@mrc.gm), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum hepcidin level (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jan 2020; AzTrials last refreshed its copy on 6 Nov 2026.