Iron Deficiency, Anaemia in ChildrenNCT04095884
An Observational Study Designed to Elucidate the Pathways by Which Inflammation Contributes to Anaemia in Sick Rural African Children From 6 Months to 36 Months
An observational study of Iron Deficiency, Anaemia in Children, run by London School of Hygiene and Tropical Medicine at 1 site in The Gambia.
Trial summary
The 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 36 months
- Conditions the study is for
- Iron Deficiency, Anaemia in Children
- What is being tested?
- blood sampling
- Type of treatment
- Surgery or procedure
- How many people
- 200 participants
- Where
- 1 siteThe Gambia
- Study dates
- 17 Jul 2019to Apr 2023
- 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 36 months
- All sexes
- No healthy volunteers
- Child
Study population: sick children with fever
Who may be able to join
- Male or female children ages 6-36 months
- Fever ( > 37.5C) and/or signs of illness.
- Signed or fingerprinted or personally marked written informed consent obtained from their parent/guardian.
- 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
- Critically unwell requiring stabilisation and transfer i.e. scores 3 on initial assessment
- Sickle cell disease
- Evidence of hookworm infection by stool microscopy
- 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).
- Administration of systemic antibiotic treatment within 3 days prior to study enrolment.
- 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). * Other than the exclusionary clinical diagnosis of malnutrition for all subjects, in children 2 to 5 years of age, malnutrition is also defined as a weight-for-height Z-score of less than -3 as per WHO reference standards.
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- Any history of human immunodeficiency virus, chronic hepatitis B or chronic hepatitis C infections.
- 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
- Participation in another MRC study
Trial locations and contacts
1 site in 1 country.
The Gambia1 site, 1 recruiting
- Recruiting
Keneba MRC Unit
West Kiang, City of Banjul, 0000
Elizabeth Ledger, MBBCh, +220 4495442-6, eledger@mrc.gm
Carla Cerami, MD
About this study
Official title: An Observational Trial Designed to Elucidate the Pathways by Which Inflammation Contributes to Anaemia in Sick Rural African Children From 6 Months to 36 Months
The 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, the investigator aim to characterise the relationship between infections, acute inflammation, hepcidin and iron iron deficiency anaemia in rural African children. The Investigator will study 200 sick children (6-36 months of age) living in the rural region of West Kiang.
The Investigator will:
- Recruit 50 sick febrile children in each of 4 categories; Upper Respiratory tract infections, Lower respiratory tract infections (pneumonia), Urinary tract infections, gastroenteritis.
- Assess iron absorption and its relationship to iron and anaemia status, inflammation, EPO, erythroferrone and hepcidin.
Read the detailed description
Aim 1: To test whether non-malarial infections increase hepcidin levels and for how long in sick children (note that the investigator exclude malaria because the investigator and others have previously examined the effect of malaria).
Hypothesis 1: On day 0, 3 and 7 of acute illness, hepcidin will be higher when compared to levels in well children. On Day 14 iron absorption and hepcidin levels will have returned to baseline.
Research Question 1: What affect do non-malarial infections (upper respiratory tract infections, lower respiratory tract infections, urinary tract infections and gastroenteritis) have on hepcidin levels and how long does this effect last?
Aim 2: To retest our existing hepcidin threshold for discriminating iron absorbers from non-absorbers by repeating our prior ROC analysis based on a much larger sample.
Hypothesis: On day 0, 3 and 7 of acute illness, iron absorption will be lower. On Day 14, iron absorption will be equivalent to iron absorption in well children. Note that the Hepcidin levels and iron absorption data obtained in this study will be compared with the results obtained from similarly aged children in IDeA Study 1 (SCC 1664). Also note that The investigator anticipate that most of the children enrolled in this study will have a base-line level of anaemia (eg Hgb<11g/dL).
Research Question: What is the relationship between hepcidin and oral iron absorption in acute illness and convalescence and how does this differ from the relationship in well children?
Aim 3: To examine EPO synthesis and EPO resistance in children with acute non-malarial infections?
Hypotheses:
- Children with acute non-malaria infections will have both acute and chronic anaemia of inflammation.
- EPO is increased during acute infection.
Research Question: Is there decreased EPO synthesis and/or increased EPO resistance in children with acute non-malarial infections living in rural Gambia?
Aim 4: To examine erythroferrone in children with acute non-malarial infections leaving in rural Gambia.
Hypothesis: First The 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). The 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 and CRP in anaemic and non-anaemic children living in rural Gambia? This is an observational study of 200 sick children who will be recruited at the Keneba clinic. Each child will be seen four times (at day 0, 3, 7 14).
200 subjects aged 6 -36m brought to Keneba clinic with an acute illness. 50 patients from each category: Upper respiratory tract infections (including ear, nose and throat infections), Lower respiratory tract infections, urinary tract infections and gastroenteritis.
- Conditions
- Iron Deficiency, Anaemia in Children
- Being tested
- blood sampling
- Medical subject headings
- Iron Deficiencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingProcedure or surgery
observational study and no intervention will be given. only blood samples collected and treated with iron supplements
| Study group | Role | What they receive |
|---|---|---|
| Urinary Tract Infection | Inclusion criteria (one from the list below):
1. Positive leukocytes, positive nitrites on dipstick
2. Negative leukocytes, Positive nitrites on dipstick
3. Positive leukocytes, negative nitrites, plus bacteriuria on microscopy
4. Positive leukocytes, negative nitrities plus no bacteriuria, only pyuria on microscopy PLUS clinical features e.g. fever, pain on urination, offensive smelling urine.
Exclusion criteria (one from the list below):
1. No evidence of UTI on dipstick Receives: Procedure: blood sampling | |
| Upper respiratory tract infection | Inclusion criteria (one from the list below)::
1. Evidence of nasal discharge AND/OR
2. Inflammation throat/ tonsils on direct examination AND/OR
3. Inflammation of middle or outer ear on direct examination
4. History of fever AND history of stridor/ barking cough
5. History of fever AND lymphadenopathy AND/ OR URTI symptoms i.e sore throat/ cough
Exclusion criteria (one from the list below)::
1. Foreign body inserted in either nose/ ear
2. Traumatic perforation of ear drum
3. Allergic rhinitis i.e. good contact history
4. Evidence of LRTI Receives: Procedure: blood sampling | |
| Lower respiratory tract infection | Inclusion criteria (one from the list below):
1. Focal signs on auscultation of the chest i.e crepitations/ wheeze/ reduced air entry
2. Fever > 38.5C AND chest recessions AND/OR raised respiratory rate
3. Radiological evidence of LRTI
Exclusion criteria (one from the list below):
1. Positive malaria test OR suspicion of metabolic acidosis causing tachypnoea and fever Receives: Procedure: blood sampling | |
| Diarrhoea/ gastroenteritis | Inclusion criteria (one from the list below):
1. Abrupt onset of 3 or more loose/liquid stools/ day
2. Ova, cysts, parasites identified on stool microscopy PLUS symptomatic diarrhoea,and/ or fever and/or vomiting
3. Fever AND vomiting WITHOUT other source of fever i.e UTI/LRTI/URTI
Exclusion criteria (one from the list below):
1. Normal breast milk stool
2. Neurological cause of vomiting Receives: Procedure: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum hepcidin from baseline to day 14
Measured: Day 14
Change in Clinical score of site and severity of infection and inflammation from baseline to day 14
Measured: Day 14
Secondary outcomes (3)
serum iron levels
Increase in serum iron levels above baseline following an oral ferrous fumarate dose as a measure of iron absorption
Measured: Day 0, 3, 7 & 14
Erythropoietin
Measured: Day 0, 3, 7 & 14
Erythroferrone
Measured: Day 0, 3, 7 & 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2019
- Study start17 Jul 2019
- Primary completionJan 2023 (estimated)
- Study completionApr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron Deficiency, Anaemia in ChildrenStudies 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
- 200 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
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04095884
- Sponsor's protocol ID
- SCC 17097
- Status last verified
- Jan 2020
- First submitted
- 4 Sep 2019
- Last updated
- 9 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- 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 Trial Designed to Elucidate the Pathways by Which Inflammation Contributes to Anaemia in Sick Rural African Children From 6 Months to 36 Months
- ClinicalTrials.gov ID
- NCT04095884
- Acronym / sponsor ID
- SCC 17097
- Conditions
- Iron Deficiency, Anaemia in Children
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 19 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.
The 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, the investigator aim to characterise the relationship between infections, acute inflammation, hepcidin and iron iron deficiency anaemia in rural African children. The Investigator will study 200 sick children (6-36 months of age) living in the rural region of West Kiang.
The Investigator will:
- Recruit 50 sick febrile children in each of 4 categories; Upper Respiratory tract infections, Lower respiratory tract infections (pneumonia), Urinary tract infections, gastroenteritis.
- Assess iron absorption and its relationship to iron and anaemia status, inflammation, EPO, erythroferrone and hepcidin.
Detailed description
Aim 1: To test whether non-malarial infections increase hepcidin levels and for how long in sick children (note that the investigator exclude malaria because the investigator and others have previously examined the effect of malaria).
Hypothesis 1: On day 0, 3 and 7 of acute illness, hepcidin will be higher when compared to levels in well children. On Day 14 iron absorption and hepcidin levels will have returned to baseline.
Research Question 1: What affect do non-malarial infections (upper respiratory tract infections, lower respiratory tract infections, urinary tract infections and gastroenteritis) have on hepcidin levels and how long does this effect last?
Aim 2: To retest our existing hepcidin threshold for discriminating iron absorbers from non-absorbers by repeating our prior ROC analysis based on a much larger sample.
Hypothesis: On day 0, 3 and 7 of acute illness, iron absorption will be lower. On Day 14, iron absorption will be equivalent to iron absorption in well children. Note that the Hepcidin levels and iron absorption data obtained in this study will be compared with the results obtained from similarly aged children in IDeA Study 1 (SCC 1664). Also note that The investigator anticipate that most of the children enrolled in this study will have a base-line level of anaemia (eg Hgb<11g/dL).
Research Question: What is the relationship between hepcidin and oral iron absorption in acute illness and convalescence and how does this differ from the relationship in well children?
Aim 3: To examine EPO synthesis and EPO resistance in children with acute non-malarial infections?
Hypotheses:
- Children with acute non-malaria infections will have both acute and chronic anaemia of inflammation.
- EPO is increased during acute infection.
Research Question: Is there decreased EPO synthesis and/or increased EPO resistance in children with acute non-malarial infections living in rural Gambia?
Aim 4: To examine erythroferrone in children with acute non-malarial infections leaving in rural Gambia.
Hypothesis: First The 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). The 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 and CRP in anaemic and non-anaemic children living in rural Gambia? This is an observational study of 200 sick children who will be recruited at the Keneba clinic. Each child will be seen four times (at day 0, 3, 7 14).
200 subjects aged 6 -36m brought to Keneba clinic with an acute illness. 50 patients from each category: Upper respiratory tract infections (including ear, nose and throat infections), Lower respiratory tract infections, urinary tract infections and gastroenteritis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Urinary Tract Infection | – | Procedure: blood samplingInclusion criteria (one from the list below): 1. Positive leukocytes, positive nitrites on dipstick 2. Negative leukocytes, Positive nitrites on dipstick 3. Positive leukocytes, negative nitrites, plus bacteriuria on microscopy 4. Positive leukocytes, negative nitrities plus no bacteriuria, only pyuria on microscopy PLUS clinical features e.g. fever, pain on urination, offensive smelling urine. Exclusion criteria (one from the list below): 1. No evidence of UTI on dipstick |
| Upper respiratory tract infection | – | Procedure: blood samplingInclusion criteria (one from the list below):: 1. Evidence of nasal discharge AND/OR 2. Inflammation throat/ tonsils on direct examination AND/OR 3. Inflammation of middle or outer ear on direct examination 4. History of fever AND history of stridor/ barking cough 5. History of fever AND lymphadenopathy AND/ OR URTI symptoms i.e sore throat/ cough Exclusion criteria (one from the list below):: 1. Foreign body inserted in either nose/ ear 2. Traumatic perforation of ear drum 3. Allergic rhinitis i.e. good contact history 4. Evidence of LRTI |
| Lower respiratory tract infection | – | Procedure: blood samplingInclusion criteria (one from the list below): 1. Focal signs on auscultation of the chest i.e crepitations/ wheeze/ reduced air entry 2. Fever > 38.5C AND chest recessions AND/OR raised respiratory rate 3. Radiological evidence of LRTI Exclusion criteria (one from the list below): 1. Positive malaria test OR suspicion of metabolic acidosis causing tachypnoea and fever |
| Diarrhoea/ gastroenteritis | – | Procedure: blood samplingInclusion criteria (one from the list below): 1. Abrupt onset of 3 or more loose/liquid stools/ day 2. Ova, cysts, parasites identified on stool microscopy PLUS symptomatic diarrhoea,and/ or fever and/or vomiting 3. Fever AND vomiting WITHOUT other source of fever i.e UTI/LRTI/URTI Exclusion criteria (one from the list below): 1. Normal breast milk stool 2. Neurological cause of vomiting |
Who may qualify
- Ages
- 6 to 36 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- sick children with fever
Key inclusion criteria (4 listed)
- Male or female children ages 6-36 months
- Fever ( > 37.5C) and/or signs of illness.
- Signed or fingerprinted or personally marked written informed consent obtained from their parent/guardian.
- 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)
- Critically unwell requiring stabilisation and transfer i.e. scores 3 on initial assessment
- Sickle cell disease
- Evidence of hookworm infection by stool microscopy
- 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).
- 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.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingobservational study and no intervention will be given. only blood samples collected and treated with iron supplements | Procedure or surgery | Diarrhoea/ gastroenteritis, Lower respiratory tract infection, Upper respiratory tract infection, Urinary Tract Infection |
Primary outcome
Change in Serum hepcidin from baseline to day 14
Time frame: Day 14
Change in Clinical score of site and severity of infection and inflammation from baseline to day 14
Time frame: Day 14
3 secondary outcomes
serum iron levels
Time frame: Day 0, 3, 7 & 14
Erythropoietin
Time frame: Day 0, 3, 7 & 14
Erythroferrone
Time frame: Day 0, 3, 7 & 14
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.
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 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 4 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 (00220-4495442-6, ccerami@mrc.gm), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Serum hepcidin from baseline to day 14 (time frame: Day 14). 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.