Patients with high risk findings undergoing surveillance in the national Bowel Cancer Screening Programme Digestive System ‘high risk’ findings after completion of a BCSP screening episode, large non-pedunculated colorectal polyp
Conditions
Interventions
For the Main trial, participants are randomised in a 1:1 ratio and have an equal chance of receiving one of the following therapies:
Therapy1 – aspirin tablet
Therapy 2 – aspirin tablet and metformin
Sponsors
University of Leicester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 28/07/2025: General inclusion criteria for both trials: 1. Patients with high risk findings (=2 premalignant polyps including =1 advanced colorectal polyp; or =5 premalignant polyps) at a completed screening episode according to BCSP criteria 2. Patients with a large (=20mm) non-pedunculated colorectal polyp that is resected with histological R0 en bloc excision at a completed screening episode 3. Patients with a large (=20mm) non-pedunculated colorectal polyp after piecemeal excision. These will only be eligible if the 2nd site check is a full clearance colonoscopy 4. Adequate renal function, defined as GFR =45ml/min/1.73m2, at any time in the preceding 4 weeks 5. Willing and able to consent to participate in trial Inclusion criteria for the main trial but not the resveratrol Signal-Seeking trial: 6. Aged 50-71 years Additional inclusion criteria for the resveratrol Signal-Seeking trial only: 7. Aged 50-74 years 8. Use of aspirin, including as an anti-platelet therapy, is permitted in the signal-seeking trial _____ Previous inclusion criteria: General inclusion criteria for both trials: 1. Patients with high risk findings (=2 premalignant polyps including =1 advanced colorectal polyp; or =5 premalignant polyps) at a completed screening episode according to BCSP criteria 2. Patients with a large (=20mm) non-pedunculated colorectal polyp that is resected with histological R0 en bloc excision at a completed screening episode 3. Patients with a large (=20mm) non-pedunculated colorectal polyp after piecemeal excision. These will only be eligible if the 2nd site check is a full clearance colonoscopy 4. Adequate renal function, defined as GFR =45ml/min/1.73m2, at any time in the preceding 4 weeks 5. Willing and able to consent to participate in trial Inclusion criteria for the main trial but not the resveratrol Signal-Seeking trial: 6. Aged 50-71 years Additional inclusion criteria for the resveratrol Signal-Seeking trial only: 7. Aged 50-73 years 8. Use of aspirin, including as an anti-platelet therapy, is permitted in the signal-seeking trial
Exclusion criteria
Exclusion criteria: General exclusion criteria for both trials: 1. Malignant change in a polyp. 2. Known clinical diagnosis or gene carrier of a hereditary CRC predisposition (FAP, hereditary nonpolyposis CRC). 3. Previous or newly diagnosed inflammatory bowel disease. 4. Previous or planned colorectal resection. 5. Known bleeding diathesis or concomitant non-aspirin anti-coagulant or anti-platelet agent. 6. Abnormal liver functions consisting of any of the following, at any time in the preceding 4 weeks: 6.1. Serum bilirubin =1.5 x ULN (except for participants with Gilbert’s disease, for whom the upper limit of serum bilirubin is 51.3µmol/l or 3mg/dl) 6.2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2.5 x ULN 7. Inability to comply with trial procedures and use of therapies. 8. Pregnant or lactating women. Women of child-bearing potential must agree to use appropriate methods of birth control (see protocol section 8.6) 9. Males with partners who are WOCBP and are unwilling to use effective methods of contraception 10. Serious medical illness interfering with trial participation including inability to have future colonoscopic surveillance. 11. Participants who have been administered an investigational medicinal product for another research trial in the last 30 days or =5 elimination half-lives. Exclusion criteria for the main trial but not the resveratrol Signal-Seeking trial: 12. Regular (>3 doses per week) prescribed or ‘over the counter’ (OTC) aspirin or regular (>3 doses per week) prescribed or OTC non-aspirin NSAID use. 13. Allergic or intolerant to ibuprofen or naproxen, metformin, aspirin or salicylate. 14. Diabetic patients on drug treatment. 15. Current or previous treatment with metformin 16. Known history of peptic ulcer disease. 17. Known history of lactic acidosis or predisposing conditions. 18. Prior use of NSAIDs is not an exclusion if they are self-prescribed and the patient is willing to stop use for the duration of the trial. 19. Use of long-term systemic corticosteroids Additional exclusion criteria for the resveratrol Signal-Seeking trial only 20. Unable to abstain from ingestion of OTC supplements containing resveratrol for the trial duration. 21. Known yeast allergy 22. Sensitivity or allergy to any of the capsule excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Polyp number measured by MPP (Mean number of Polyps per Participant) at exit surveillance colonoscopy 154 weeks for main trial 52 weeks for sub-trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured at exit surveillance Colonoscopy (154 weeks for main trial; 52 weeks for sub-trial). 1. Polyp Detection Rate (PDR, proportion of individuals with one or more qualifying* pre-malignant polyp(s) at surveillance) 2. Advanced polyps (measured as MPP and PDR); these are defined as serrated polyp =10mm, serrated polyp with any dysplasia, adenoma =10mm, adenoma with high-grade dysplasia 3. Polyp subtype based on histopathology (adenoma/serrated); also reported as MPP and PDR 4. Location of polyps (right colon - any part of the colon proximal to the splenic flexure; left colon – the rectum and the colon distal to and including the splenic flexure) 5. Polyp size (maximum dimension in mm as described in the histopathology report or endoscopic size if no histopathological size available) Safety measured from first administration of IMP until the final visit at 156 weeks for the main trial and 54 weeks for the sub-trial: 6. Adverse events, including clinically significant bleeding episodes and GI tolerability. Compliance measured in the main trial at: weeks 25, 52, 78, 104, 130 and 154; resveratrol sub-trial at: weeks 25 and 52 7. Assessment of compliance by counting residual numbers of tablets/capsules returned by each patient. Exploratory endpoints 8. Measurement of molecular (glucose, insulin (HOMA), HbA1c, triglycerides, cholesterol, IGFBP-3, free IGF-1) and physical (BMI, waist circumference) markers of metabolic status. 9. Assessment of dietary patterns and fat intake using the EPIC FFQ. 10. Plasma drug concentrations and metabolite profile for resveratrol and metformin. 11. Urinary resveratrol/metabolite levels in 20% of participants in the sub-trial from randomly selected sites that are willing and able to collect urine samples. 12. In the main trial: Measurement of pharmacodynamic biomarkers common to both aspirin and metformin, including p65, pS6/S6 and cleaved PARP in tissue samples. 13. In the resveratrol sub-trial: Analysis of tissue and plasma pharma | — |
Countries
United Kingdom
Outcome results
None listed