Study Stopped
withdrawn prior to gaining approvals
Molecular Effects of Aspirin & Metformin on Colonic Epithelium
1 other identifier
interventional
N/A
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Aug 2022
Shorter than P25 for not_applicable colorectal-cancer
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 17, 2021
CompletedFirst Posted
Study publicly available on registry
December 15, 2021
CompletedStudy Start
First participant enrolled
August 1, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2023
CompletedFebruary 6, 2025
June 1, 2024
2 months
November 17, 2021
February 3, 2025
Conditions
Outcome Measures
Primary Outcomes (12)
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 24 hours Aspirin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 7 days Aspirin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 28 days Aspirin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 6 weeks Aspirin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 24 hours Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 7 days Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 28 days Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 6 weeks Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 24 hours combined Aspirin and Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 7 days combined Aspirin and Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 28 days combined Aspirin and Metformin medication
Relative genetic expression change of genes relating to energy, metabolism and stem cell signalling in the large bowel
Effect on genetic expression
Baseline and immediately after 6 weeks combined Aspirin and Metformin medication
Secondary Outcomes (24)
Change in value of qFIT result with aspirin, metformin or combination
Baseline and immediately after 24 hours Aspirin medication
Change in value of qFIT result with aspirin, metformin or combination
Baseline and immediately after 7 days Aspirin medication
Change in value of qFIT result with aspirin, metformin or combination
Baseline and immediately after 28 days Aspirin medication
Change in value of qFIT result with aspirin, metformin or combination
Baseline and immediately after 6 weeks Aspirin medication
Change in value of qFIT result with aspirin, metformin or combination
Baseline and immediately after 24 hours Metformin medication
- +19 more secondary outcomes
Study Arms (13)
Control
NO INTERVENTIONNo medication, 6 weeks
Aspirin 24 Hours
ACTIVE COMPARATOR24 Hours Aspirin
Aspirin 7 Days
ACTIVE COMPARATOR7 Days Aspirin
Aspirin 28 Days
ACTIVE COMPARATOR28 Days Aspirin
Aspirin 6 Weeks
ACTIVE COMPARATOR6 Weeks Aspirin
Metformin 24 Hours
ACTIVE COMPARATOR24 Hours Metformin
Metformin 7 Days
ACTIVE COMPARATOR7 Days Metformin
Metformin 28 Days
ACTIVE COMPARATOR28 Days Metformin
Metformin 6 Weeks
ACTIVE COMPARATOR6 Weeks Metformin
Aspirin & Metformin 24 Hours
ACTIVE COMPARATOR24 Hours Aspirin \& Metformin
Aspirin & Metformin 7 Days
ACTIVE COMPARATOR7 Days Aspirin \& Metformin
Aspirin & Metformin 28 Days
ACTIVE COMPARATOR28 Days Aspirin \& Metformin
Aspirin & Metformin 6 Weeks
ACTIVE COMPARATOR6 Weeks Aspirin \& Metformin
Interventions
75mg Aspirin once per day
500mg Metformin once per day
75mg Aspirin and 500mg Metformin once per day
Eligibility Criteria
You may qualify if:
- All participants who are capable of giving informed consent. All participants aged 16 years or over. All participants must have no known contraindications to rectal biopsy procedures.
- All participants must be resident in the United Kingdom. All participants must have no known contraindications to aspirin and metformin.
You may not qualify if:
- Unable to give informed consent. Under the age of 16 years. Individuals who are taking anti-coagulation medication. Individuals with platelet disease or other bleeding issues. Individuals with a history of a significant rectal bleed. History of diabetes mellitus or impaired glucose tolerance. Any contraindication to either aspirin or metformin. Female subjects of child bearing age who are not taking effective contraception during the period of the trial
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Farhat VN Din, FRCSed
University of Edinburgh
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 17, 2021
First Posted
December 15, 2021
Study Start
August 1, 2022
Primary Completion
October 1, 2022
Study Completion
June 1, 2023
Last Updated
February 6, 2025
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will not share