Mechanisms affecting the gut of preterm infants
| ISRCTN | ISRCTN12554594 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12554594 |
| Secondary identifying numbers | CPMS 30750 |
- Submission date
- 18/05/2016
- Registration date
- 01/08/2016
- Last edited
- 12/09/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
About 11% of all babies born worldwide are preterm (premature), meaning that they are born more than three weeks before their due date. The earlier babies are born, the more likely they are to die or develop long-term complications, particularly those born before 32 weeks. Over the last 20 years, breathing support has improved significantly, meaning that more babies now service. Currently, the most common cause of serious illness after the first week are due to complications or infections in the gut (digestive system). About 20-25% of very preterm infants (born before 32 weeks) develop a serious infection (sepsis) or a bowel complication called necrotising enterocolitis (NEC). Infants who get sepsis or NEC have a much higher risk of dying or being disabled. Better methods of preventing these complications in very preterm infants are needed. The ELFIN study started recruiting infants in 2015, and will test whether giving them supplemental lactoferrin (a natural antibiotic protein from cow's milk) reduces the number of serious infections, and also whether it affects rates of gut complications. Regardless of the results of the ELFIN study, the way that the extract lactoferrin works on the gut will still be unknown. It is thought that lactoferrin will work by changing the pattern of bacteria in the gut, and that in turn this will reduce the number of harmful bacteria that might cause sepsis. Increasing the number of healthy bacteria in the gut may allow the infant to better tolerate milk feeds, and less likely to develop gut complications such as NEC. The aim of this study is to find out how lactoferrin supplements work by looking at changes to the gut bacteria.
Who can participate?
Premature babies who are taking part in the ELFIN study of lactoferrin.
What does the study involve?
Details about the ELFIN trial are available at: http://www.isrctn.com/ISRCTN88261002.
For all participants, a sample of stool is collected from the nappy, and a urine sample (collected using cotton wool balls) each day the baby is in the hospital until they are close to going home. These samples are then stored at the local hospital before being transferred to central laboratories in Newcastle. The samples are analysed for the overall patterns of gut bacteria, as well as the presence of specific species that may be harmful or associated with improved recovery.
What are the possible benefits and risks of participating?
There are no direct benefits or risks involved for participants taking part in this study.
Where is the study run from?
The Neonatal Unit at Royal Victoria Infirmary (lead centre) and ten other neonatal units in NHS hospitals in the north of England (UK)
When is the study starting and how long is it expected to run for?
February 2016 to June 2019
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Nicholas Embleton
Contact information
Public
The Royal Victoria Infirmary
Ward 35 RVI
Newcastle Hospitals NHS Foundation Trust
Newcastle Upon Tyne
NE1 4LP
United Kingdom
Study information
| Study design | Observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Mechanisms Affecting the Gut of Preterm Infants in Enteral feeding trials (MAGPIE) |
| Study acronym | MAGPIE |
| Study objectives | The aim of this study is to determine, in preterm infants, whether the mechanism of action of enteral lactoferrin supplementation in reducing infections or gut complications involves changes in the pattern of gut bacteria. This study is linked to the ELFIN – Enteral Lactoferrin in Neonates study (available via http://www.isrctn.com/ISRCTN88261002) |
| Ethics approval(s) | East Midlands - Nottingham 2 Research Ethics Committee, 16/03/2016, ref: 16/EM/0042 |
| Health condition(s) or problem(s) studied | Specialty: Children, Primary sub-specialty: Neonatal; UKCRC code/ Disease: Oral & Gastro/ Other diseases of the digestive system |
| Intervention | Infants who join the trial will all have been enrolled in the ELFIN study, and are anticipated to be recruited to MAGPIE at the same time in most cases i.e. within the first few days after delivery. We will collect a daily stool and urine sample from the infants from recruitment until hospital discharge (average 6 weeks, range 3-12 weeks in total duration). These samples will be collected at the cot-side and then placed in a freezer on the neonatal intensive care unit (NICU). Samples will be transferred to central laboratories and the most informative samples chosen for analysis of gut microbiota (16s next generation sequencing) and metabolomic analysis (stool and urine). |
| Intervention type | Other |
| Primary outcome measure | Gut microbial diversity (Shannon Diversity Index) and differences in the proportions of key bacterial taxa measured using 16s next generation sequencing in stool samples collected after enrolment on days 1-3, 7, 10-14, and 21 (+/- 1) days. |
| Secondary outcome measures | 1. The association between the pattern of gut microbiota and the stool metabolome using mixed effect models, structural equation modelling and ordination analyses. Stool metabolome is measured using Gas Chromatography and/or Liquid Chromatography in samples collected on days 1-3, 7, 10-14, and 21 (+/- 1) days. 2. Pattern of gut microbiota prior to the onset of NEC or sepsis (diagnosed according to criteria used in the ELFIN trial) is measured using up to 7 daily stool samples in the period immediately prior to disease compared to samples from control cases who do not develop disease 3. The gut tissue inflammatory response in surgically resected gut tissue affected by NEC and in control tissue (either non-affected tissue from the same infant, or tissue from an infant requiring gut resection who does not have disease), is determined by immune-histochemistry using paraffin blocks cut into small sections for staining, a digital slide scanner and white cell infiltrates identified using antibodies. This is measured after trial completion by retrieving samples from hospital pathology archives. |
| Overall study start date | 01/02/2016 |
| Completion date | 30/06/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | Planned Sample Size: 480; UK Sample Size: 480 |
| Total final enrolment | 479 |
| Key inclusion criteria | Preterm infants <32 weeks gestation who have been enrolled into the ELFIN study of lactoferrin |
| Key exclusion criteria | Lack of informed consent |
| Date of first enrolment | 01/07/2016 |
| Date of final enrolment | 30/06/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Richardson Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
Kayll Road
Sunderland
SR4 7TP
United Kingdom
Hardwick Road
Stockton
TS19 8PE
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Great George Street
Leeds
LS1 3EX
United Kingdom
Bradford
BD9 6RJ
United Kingdom
Queen Elizabeth Medical Centre
Mindelsohn Way
Birmingham
B15 2TG
United Kingdom
Hucknall Road
Nottingham
NG5 1PW
United Kingdom
Queen's Medical Centre Campus
Derby Road
Nottingham
NG7 2UH
United Kingdom
Jessop Wing
Tree Root Walk
Sheffield
S10 2SF
United Kingdom
Sponsor information
Hospital/treatment centre
Newcastle Joint Research Office
1st Floor Regent Point
Regent Farm Road
Gosforth
Newcastle-Upon-Tyne
NE3 3HD
England
United Kingdom
"ROR" |
https://ror.org/05p40t847 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Planned publication of a protocol in 2017 and the first stage analysis (effects on gut microbiota) in 2019 in a relevant peer reviewed journal. Metabolomic and integrative analysis, and tissue analysis publication will be in 2019-2020. It is anticipated that the preliminary results will be presented at international conferences. However, because this is an embedded mechanistic study, no key (un-blinded) data collected as part of MAGPIE will be presented or published until the primary results of the ELFIN trial have been accepted for publication. |
| 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 | 08/05/2017 | Yes | No | |
| Results article | 01/09/2021 | 26/10/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Results article | 17/11/2022 | 12/09/2024 | Yes | No |
Editorial Notes
12/09/2024: Publication reference and total final enrolment added.
26/10/2022: Publication reference added.
24/05/2017: Publication reference added.
