Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05605353 |
| Other study ID # |
2-066-22 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2023 |
| Est. completion date |
May 31, 2029 |
Study information
| Verified date |
May 2023 |
| Source |
University of Aberdeen |
| Contact |
George Ramsay, FRCS |
| Phone |
03454566000 |
| Email |
george.ramsay[@]abdn.ac.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The large intestine is the last part of the digestive tract. It absorbs water and dietary
substances. However, it is also where most of our bacteria are resident. These bacteria are
important for our health and influence many different diseases, including Colon Cancer,
Ulcerative Colitis and Crohn's disease. The gut bacteria can also potentially influence
responses to treatments in other cancers by helping to change the responses to radiotherapy
and chemotherapy. The interactions between these bacteria and the rest of our cells are only
now becoming understood and there is little research on the interactions between these
bacteria and cancer radiotherapy treatments in pelvic cancer.
We will therefore explore this in more detail. We will ask for samples of the patient's poo
before their treatment for pelvic cancers. This will include patients with bladder, prostate,
cervical, ovarian, womb or colorectal cancers. By doing so we will be able to compare the
profile of gut bacteria with responses to treatments, thereby increasing our understanding of
the colonic bacteria.
To do this we process the poo specimens to remove the bacterial genetic material (DNA) of the
bacteria and process it on a machine to read the genetic code and also study the metabolites
that they will produce. We can then make a direct comparison between different samples of the
relative numbers of different bacteria present. In some cases, we will compare this to
metabolites and inflammatory and immune markers identified in a blood sample. This work might
help future patients by determining what are the best bacteria to have in the colon during
cancer treatments. These could potentially be given to patients, before their cancer
treatment, in the form of probiotic medications, should there be an improvement demonstrated
in our research. Alternatively we could alter the patients' intakes of specific dietary
fibres to boost these bacteria specifically.
Description:
The University of Aberdeen and Aberdeen Royal Infirmary (ARI) in NHS Grampian are in the
unique position of having a single site campus for microbiota-related laboratory science at
the world-famous Rowett Institute, Biorepository facilities on campus for rapid sample
processing and NHS facilities for treatment of multiple pelvic tumour types, including
colorectal, gynaecological and urological.
Patients will be approached in their respective pelvic cancer clinics, after identification
for potential inclusion at the respective multi-disciplinary team (MDT) meeting. The patient
will be informed of their diagnosis and management plan by a clinician responsible for their
care (may include Clinical Nurse Specialist). Patients will only be approached about the
research at a subsequent meeting, e.g. when the specialist nurses contact the patient to
address any further questions around the management plan discussed, they attend the
consultant clinic for consent to definitive treatment, etc. This gives the patient sufficient
time to process their diagnosis and management plan before introducing the research. At this
meeting patients will be provided with the PIS (this will be posted to the patient if the
meeting is via video teleconference). If they are willing to consider being involved, they
will then be contacted by a research nurse or other suitably qualified team member, who will
discuss the study further and answer any questions. If they are willing to take part
arrangements will be made for a member of the clinical team to obtain written informed
consent when the patient attends hospital for a subsequent clinical appointment.
They will be asked to donate a faecal sample (and in a subset of colorectal patients, a
right-sided colonic contents sample taken at the time of their operation) for processing at
the Rowett Institute Human Nutrition Unit before the start of their next cancer therapy
(chemotherapy, radiotherapy or surgery). Consent will also be sought to obtain a blood
sample. This will normally be obtained during routine venesection for clinical reasons and
will be blood surplus to clinical requirements processed by the Biorepository. Where
necessary, if blood is not being collected as part of standard clinical care, an extra
venepuncture, of 5mls, will be requested. Blood will be processed for plasma extraction.
Patients will also be encouraged to complete an optional food frequency questionnaire (FFQ)
indicating what they have eaten and drank in the three months before taking their stool
samples. However, if they feel unable to complete this, their decision will be respected and
they can continue in the study. These questionnaires take around 30 minutes to complete and
will be provided to the patients either during a clinical appointment before their first
cancer therapy or posted out to them. A subgroup of patients will also be asked if they would
be willing to provide a more in-depth assessment of their diet on the four days before
providing the stool sample but it will be highlighted to them that this is optional and they
are free to refuse.
Faecal samples will be collected from the ARI brought to the hospital on the day of a clinic
appointment or initial treatment for the patient. Alternatively, the participant can leave
the sample at a specific drop off centre in the Rowett institute. This will be left to the
discretion of the participant as to whichever is most convenient for them. Completed food
diaries/questionnaires will also be collected at the same time and in the same location as
the faecal sample drop-off.
No other additional samples are required from the patient. After obtaining the specimens, at
the Rowett Institute, a portion will be processed by Dispomix for DNA extraction using
Powersoil DNA extraction kits and stored in freezers before analysis by 16S rRNA gene
sequencing. Another portion will be processed and stored for SCFA analysis by gas
chromatography and some of the remaining faeces stored for future analyses.
Plasma will be extracted from the blood samples from the NHS Haematology laboratories and
transferred to the Rowett Institute by the research team involved in the study. In situations
where a blood sample has not been taken for clinical purposes the blood sample will be
collected by a phlebotomist or other trained staff at the Human Nutrition unit of the Rowett
Institute. Once the plasma has been extracted, the blood samples will be stored in freezers
at the Rowett Institute.
16S rRNA gene sequencing of faecal DNA will be undertaken at the Centre for Genome Enabled
Biology and Medicine (CCEBM), University of Aberdeen, including bioinformatics analysis.
Using 16S rRNA gene sequencing, a small portion of the bacterial genetic material is
examined, which differs between different bacteria, allowing us to estimate the 'relative
abundance' of each within each specimen. We will also analyse SCFAs in faeces by GC and
plasma by GC-MS (this more sensitive technique is required for plasma due to lower
concentrations of metabolites present) at the Rowett Institute Analytical facility. At the
end of this study, if sufficient sample remains in a usable condition we would like to store
this for future research. After necessary funding and approvals are obtained we may in future
investigate bacterial DNA in more detail (to species/strain level) by metagenomics and other
metabolites, e.g. tryptophan, bile acids, and inflammatory (e.g. calprotectin) and immune
markers (e.g. cytokines).
Clinical data will be pseudo-anonymised at source and collected by the research team
(including biobank staff for baseline data and, research nurses, clinical fellows,
radiographers, etc, for follow up data). This will be included in the subsequent analysis.
Tumour responses and the side effects of radiotherapy/ chemoradiotherapy or surgery will be
obtained from patient notes to look at toxicity and outcomes, and some patients will have
been asked to fill in questionnaires as part of their routine clinical follow-up, such as the
RTOG and EPIC26 (questionnaires routinely used in clinical practice).
16S rRNA gene sequencing data will be analysed by Bioinformaticians at the University of
Aberdeen specialised in handling these large data sets, to determine the richness and
relative abundance of bacteria present. Data will be stored by IT services on the High
Performance Computer Cluster and submitted to a public repository. Associations will be
studied between 16S rRNA gene sequencing data, SCFA analysis and available clinical data.
Statistical analysis will be undertaken by Statisticians from Biomathematics and Statistics
Scotland
