Biomarkers of enteropathy in infants and children with severe acute malnutrition in Nigeria

ISRCTN ISRCTN18078424
DOI https://doi.org/10.1186/ISRCTN18078424
Secondary identifying numbers UI/EC/11/0067
Submission date
11/04/2016
Registration date
29/04/2016
Last edited
22/11/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Severe acute malnutrition (SAM) is defined by the World Health Organisation (WHO) as a very low weight for height, an appearance of wasting away (wasting), or by the presence of nutritional oedema (swelling caused by a build-up of excess fluid in the body). It may be found in as many as 1 in 4 children under 5 years of age who are admitted to health facilities in poorer countries, and a recent analysis showed that malnutrition was present in half of all children admitted with severe disease and half of all in-patient deaths in young children in a Kenyan district hospital. Several studies have reported that children with SAM have an enteropathy (disease of the intestines), caused by inflammation (swelling) in the small intestine. This stops food from being digested properly and nutrients being absorbed from food, and can even mean that bacteria may be able to cross the lining of the gut to cause infection in the body. It has been found that this enteropathy continues even after children have responded well to re-feeding. It is therefore very important to identify the body’s natural chemical indicators (biomarkers) of enteropathy in order to understand its significance and also whether or not it improves with different treatments. The aim of this study is to investigate the biomarkers related to enteropathy that occurs in children with SAM.

Who can participate?
Children aged 6-59 months with SAM and non-malnourished children of the same age.

What does the study involve?
At the start of the study, information about the participants is collected from the children’s health record and their caregiver. This involves information about their health and characteristics (i.e. age, gender, ethnicity, area of residence) as well as having a physical examination and having a sample of blood taken. The first available stool sample is then collected in a sterile container by a member of the clinical team. In the laboratory, the stool and blood samples from the children with SAM are tested for chemical markers and then the results are compared to the children without SAM. The children with SAM are then followed up 3, 6 and 12 months later, when further stool samples are collected.

What are the possible benefits and risks of participating?
There are no direct benefits to participants taking part in the study. There is a small risk of bleeding, pain or bruising when blood samples are collected.

Where is the study run from?
Federal Medical Centre, Gusau (Nigeria)

When is the study starting and how long is it expected to run for?
June 2010 to February 2016

Who is funding the study?
Yakult (UK)

Who is the main contact?
Professor Stephen Allen
stephen.allen@lstmed.ac.uk

Contact information

Prof Stephen Allen
Scientific

Department of Clinical Sciences
Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L35QA
United Kingdom

ORCiD logoORCID ID 0000-0001-6675-249X
Phone +44 151 705 3752
Email stephen.allen@lstmed.ac.uk

Study information

Study designCase-control study
Primary study designObservational
Secondary study designCase-control study
Study setting(s)Hospital
Study typeOther
Participant information sheet Not available in web format; please use contact details below to request the patient information sheet
Scientific titleNon-invasive biomarkers of enteropathy in infants and children with severe acute malnutrition: A pilot study
Study objectivesThe aim of this study is to investigate biomarkers of the enteropathy that occurs in children with severe acute malnutrition (SAM).
Ethics approval(s)Joint Ethical Review Committees of the University of Ibadan/University College Hospital, 03/06/2011, ref: UI/EC/11/0067
Health condition(s) or problem(s) studiedSevere acute malnutrition (SAM)
InterventionFor the participants, demographic and clinical data and a blood sample will be collected at recruitment. Demographic and clinical data will be collected onto standard forms and include information obtained from the child’s health record and from the parents/guardians. Demographic data will include the child’s age, sex, ethnicity and area of residence (urban/rural) and number of siblings. Clinical details will include feeding history, anthropometry (length/height, weight, mid-upper arm circumference), signs of malnutrition (pedal oedema, dermatitis, thin/sparse hair / easy pluck ability, angular stomatitis, glossitis, oral aphthous ulceration, Bitot’s spots, apathy, abdominal distension) and hydration status. The first available stool following recruitment will be collected by a member of the clinical team into a sterile container.

Biomarkers of enteropathy will be assessed using several laboratory methods including an untargeted multi-platform metabolomics approach using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry applied to stool and plasma samples. GC-MS will also be performed on the headspace gases from stool samples. The composition of the stool microbiota will be assessed by 16S rRNA gene sequencing. Intestinal inflammation will be assessed in stool samples by measurement of calprotectin and lactoferrin by ELISA.

Children with SAM are followed up daily until discharge, when they attend the feeding clinic and at 3 and 6 months. Repeat stool analyses will be done weekly during admission and at the 3 and 6 month follow-ups, as well as nutritional status and presence/absence of diarrhoea in a final follow-up at 1 year.
Intervention typeOther
Primary outcome measure1. Untargeted multi-platform metabolomics (gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry) in stool (first available sample) and plasma sample (at recruitment)
2. Faecal volatile organic metabolites in headspace gas from first available stool sample
3. Intesinal inflammation by measuring stool calprotectin and lactoferrin in first available stool sample
Secondary outcome measuresStool microbiota composition is measured using 16S rRNA gene sequencing in the first available stool sample.
Overall study start date01/06/2010
Completion date29/02/2016

Eligibility

Participant type(s)Patient
Age groupChild
Lower age limit6 Months
Upper age limit59 Months
SexBoth
Target number of participants100
Total final enrolment58
Key inclusion criteriaPatients:
Children aged 6 – 59 months admitted with SAM (WHZ <-3 or MUAC <11.5 cms and/or nutritional oedema)

Controls:
Non-malnourished children aged 6 – 59 months admitted to hospital or attending out-patient clinics (MUAC >12.5 cms or WHZ score ≥ -1 and no nutritional oedema)
Key exclusion criteriaPositive for HIV
Date of first enrolment01/07/2012
Date of final enrolment30/09/2012

Locations

Countries of recruitment

  • Nigeria

Study participating centre

Federal Medical Centre
Gusau
P.M.B. 1008
Nigeria

Sponsor information

Swansea University
University/education

Singleton Park
Swansea
SA2 8PP
Wales
United Kingdom

Website http://www.swansea.ac.uk/medicine/
ROR logo "ROR" https://ror.org/053fq8t95

Funders

Funder type

Industry

Yakult

No information available

Results and Publications

Intention to publish date31/10/2016
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planPlanned publication of study results and presentation at relevant conferences.
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/02/2017 22/11/2019 Yes No

Editorial Notes

22/11/2019: The following changes have been made:
1. Publication reference added.
2. The final enrolment number was added from the reference.