Molecular Effects of Aspirin & Metformin on Colonic Epithelium
Status:
Not yet recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
Summary
Bowel cancer, a significant problem in the United Kingdom (UK) with ~ 41,000 diagnoses and ~
16,000 deaths annually, has a large preventable component (~54%). It is, in part, due to
energy imbalance within bowel cells as suggested by associated risk factors: high-fat diet,
obesity, physical inactivity and type 2 diabetes mellitus. Drugs that decrease bowel cancer
risk, like aspirin and metformin, may prevent the disease by mimicking the molecular effects
of dietary restriction and exercise.
Energy imbalance, through obesity, expands stem cells which may increase bowel cancer. We
have shown that aspirin activates an energy molecule, which increases when we exercise, and
blocks signalling associated with obesity in bowel cancer. Indeed aspirin in combination with
metformin (commonly used in diabetes) has a greater effect on this pathway than either drug
alone.
To predict which patients may benefit from aspirin and metformin, we need to discover if
these drugs may mimic healthy lifestyle changes at a cellular level and which cells are being
targeted.
This project investigates how aspirin and metformin influence energy molecules in bowel cells
to mimic beneficial effects of exercise or dietary restriction. Participants, recruited from
Western General Hospital (Edinburgh) colorectal clinics, will have bowel lining and blood
samples take initially and then depending on their assigned cohort, after; 24 hours, 7 days,
28 days or a 6-week course of aspirin, metformin or both tablets. Samples will be analysed
for energy genes (main outcome). Secondary outcomes will measure effects on quantitative
faecal immunochemical tests (qFIT), used to detect blood in the stool, and on gut bacteria.
This critical research will inform how aspirin and metformin can be used in specific
populations to decrease bowel cancer risk and to develop new drugs to target abnormal energy
pathways.