Investigating the impact of surgical operations on the human immune system
| ISRCTN | ISRCTN13131952 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13131952 |
| IRAS number | 347577 |
| Secondary identifying numbers | IRAS 347577, UKRI MRC Grant ref: MR/X007243/1 |
- Submission date
- 25/09/2024
- Registration date
- 16/10/2024
- Last edited
- 27/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Surgery
Plain English summary of protocol
Background and study aims
Following surgery, some patients develop hospital-acquired infections whilst others do not. The development of infections can increase a patient’s length of stay in hospital. The immune system, which protects against infections, is made up of cells called white blood cells. Previous studies have demonstrated that following surgery, the white blood cells of patients who develop infections show reduced function when compared to the white blood cells of patients who do not develop infections. However, it is currently unclear as to why this is. To help fight against infections, white blood cells require energy. This study will acquire blood samples from patients before and after their operation to allow an examination of how surgery impacts the ability of white blood cells to make energy and fight against infection. It is thought that white blood cells from patients who develop infections after surgery will generate less energy than white blood cells from patients who do not develop infections and that this lack of energy is associated with the reduced function of the immune system. This study aims to improve the understanding of why infections develop after surgery. By increasing the understanding of this, it may be possible to develop treatments to increase the function of white blood cells after surgery that would reduce the risk of developing infections and improve patient outcomes such as reducing lengths of hospital stay.
Who can participate?
Adult patients aged between 18 and 65 years old who are undergoing elective surgery for abdominal wall reconstruction.
What does the study involve?
Patients undergoing elective surgery will provide two blood samples: one before and one after their surgery. The immune response caused by the operation will be examined by studying the functional activity of immune cells in these samples and recording the numbers and types of immune cells present.
What are the possible benefits and risks of participating?
Participation in this research study will help improve the understanding of how surgical interventions impact the immune system. Enhancing the knowledge in this area of research could help improve the management and treatment of future surgical patients by reducing their risk of developing infections.
There are no risks to taking part in this study over and above the normal risks associated with this form of elective surgery. When taking the blood sample, there may be slight discomfort of the needle being inserted into a vein and the possibility of bruising developing afterwards around the area where the needle was inserted. This should disappear in a few days.
Where is the study run from?
The University of Birmingham Research Laboratories within the Queen Elizabeth Hospital Birmingham.
When is the study starting and how long is it expected to run for?
July 2024 to March 2028
Who is funding the study?
Medical Research Council
Who is the main contact?
Dr Jon Hazeldine, j.hazeldine@bham.ac.uk)
Contact information
Public, Scientific, Principal Investigator
University of Birmingham, Edgbaston
Birmingham
B15 2TT
United Kingdom
 ORCID ID |
0000-0002-4280-4889 |
|---|---|
| Phone | +44 (0)121 371 3264 |
| j.hazeldine@bham.ac.uk |
Study information
| Study design | Observational cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Investigating the immune response in patients undergoing surgery |
| Study objectives | Traumatic injuries are known to cause activation and suppression of the immune system. However, owing to the nature of these injuries, it is not possible to analyse the immune system of a trauma patient before their injury occurs. Surgical operations cause tissue damage similar to that experienced during a traumatic injury. By obtaining a blood sample before and after a surgical operation, this study will allow for the effect of trauma to be analysed directly as the blood sample taken prior to surgery will allow for the analysis of the immune system before a trauma occurs. This immune response can then be compared to that measured in the blood sample taken following the operation. |
| Ethics approval(s) | Approved 17/12/2024, East Midlands - Leicester South Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; 02071048193; leicestersouth.rec@hra.nhs.uk), ref: 24/EM/0284 |
| Health condition(s) or problem(s) studied | Patients undergoing elective surgery |
| Intervention | Two blood samples will be taken from elective surgery patients; one before surgery and the second following the completion of the operation. Blood samples will be subjected to laboratory analysis examining the immune and inflammatory response to the surgical intervention. This analysis will involve studying the function of immune cells, their number and the mechanisms that underlie the changes that occur. |
| Intervention type | Other |
| Primary outcome measure | The metabolic activity of neutrophils and monocytes isolated from blood samples obtained from elective surgery patients will be measured by flow cytometry, enzyme-linked immunosorbent assays and metabolic tracing before and after their operation |
| Secondary outcome measures | The following secondary outcome measures will be assessed in blood samples obtained from elective surgery patients before and after their operations: 1. Anti-microbial activities and surface phenotype of isolated neutrophils, monocytes and/or peripheral blood mononuclear cells (in the absence and/or presence of ex vivo stimulation) will be measured using flow cytometry 2. Circulating markers of inflammation (e.g. pro-inflammatory cytokines, acute phase proteins, cell-free DNA, Damage-associated molecular patterns, whole blood cell counts) will be measured using enzyme-linked immunosorbent assays, whole blood cell haematological analysers and fluorometric-based assays 3. DNA and RNA epigenetic profiles of neutrophils and peripheral blood mononuclear cells RNA sequencing, DNA methylation assays and real-time polymerase chain reaction (RT-PCR) experiments |
| Overall study start date | 26/07/2024 |
| Completion date | 01/03/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | 1. Male or female patients aged 18-65 years 2. Patient able to give informed consent 3. Patient undergoing elective open abdominal wall reconstruction surgery |
| Key exclusion criteria | 1. Under the age of 18 years and over the age of 65 years 2. A known malignancy 3. Pregnancy 4. The operation is contaminated (e.g. there is a bowel resection +/- anastomosis, iatrogenic bowel injury or presence of a stoma) 5. Minimally invasive (laparoscopic or robotic) surgery 6. Significant anaesthetic complication (such as anaphylaxis, malignant hyperthermia, negative pressure pulmonary oedema) |
| Date of first enrolment | 26/05/2025 |
| Date of final enrolment | 01/03/2028 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Sponsor information
University/education
Ash House, 353 Bristol Road, Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)7814 650003 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/03/2029 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository, Available on request |
| Publication and dissemination plan | The results generated from this study will be shared with the wider scientific community. This will take the form of published articles in peer-reviewed journals and presentations at national and international conferences. |
| IPD sharing plan | 1. The datasets generated during and/or analysed during the current study will be available upon request from Dr Jon Hazeldine (j.hazeldine@bham.ac.uk). 2. The datasets generated during and/or analysed during the current study will be stored in a publicly available repository. Specifically, RNA sequencing data will be made available through the public repository Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo). Data will be uploaded concurrent to the acceptance of the study associated manuscript that presents data derived from RNA sequencing analysis. Patients who agree to participate in the study will have been provided with a patient information sheet that details how the data derived from the analysis of their samples will be presented as part of scientific literature in an anonymised manner which means it will not be possible to identify them as individuals. |
Editorial Notes
27/05/2025: The recruitment start date was changed from 01/05/2025 to 26/05/2025.
24/01/2025: The following changes were made to the trial record:
1. The ethics approval was added.
2. The recruitment start date was changed from 01/01/2025 to 01/05/2025.
25/11/2024: Sponsor contact was updated.
26/09/2024: Study's existence confirmed by the UKRI MRC.
