Ageing Other
Conditions
Interventions
TRIAL DESIGN
A Phase IIa clinical trial of a 3-week intervention of one of three geroprotector drugs: metformin MR, fisetin or spermidine. This is an uncontrolled trial with no placebo arm. The outco
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
70 Years to 110 Years
Inclusion criteria
Inclusion criteria: 1. Age =70 years 2. Ability to provide informed consent 3. Able to travel to the clinic for initial and subsequent evaluations 4. Ability to understand spoken and written English
Exclusion criteria
Exclusion criteria: 1. Current smokers, or ex-smokers who have stopped within the last 12 months, or are using nicotine replacement products 2. History of diabetes (type 1 or 2), or untreated vitamin B12 deficiency 3. Untreated thyroid disorder 4. Active cancer - currently on treatment or palliative 5. Major surgery or trauma in the last 60 days 6. Recent infection in the last 60 days 7. Allergies or intolerance to any of the drugs to be studied 8. Any contraindication to metformin MR, as listed in the current summary of medicinal product characteristics for metformin MR 9. Any medication which significantly interacts with metformin MR, as listed in the current summary of medicinal product characteristics for metformin MR 10. Currently taking any of the following medications, which confound the effects of inflammation: tamoxifen, cyclosporine A, immunosuppressants or Anti TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs). 11. Currently taking any of the following anticoagulant drugs (blood thinners): warfarin, direct oral anticoagulant drugs (DOACs), low molecular weight heparin, clopidogrel, or high-dose aspirin. Patients taking low dose =75 mg aspirin only may be recruited 12. Individuals at risk of bleeding complications, including those with inherited bleeding disorders (such as haemophilia), or previously unexplained haemorrhage 13. Unable or unwilling to maintain current lifestyle throughout trial such as eating habits, exercise habits, etc 14. Estimated glomerular filtration rate 48 hours of Bristol stool chart grade 6 or 7) 16. Liver function tests (bilirubin, alanine aminotransferase or alkaline phosphatase) >3× upper limit of normal 17. Symptomatic chronic heart failure, diagnosed according to European Society of Cardiology guidelines (asymptomatic left ventricular systolic dysfunction will not be an exclusion criterion) 18. Life expectancy of <3 months as adjudicated by the local Investigator 19. Previous inclusion in trial investigating effects of ‘geroprotector’ medication 20. Allergy to local anaesthetic 21. Coeliac disease (spermidine only) 22. Contrast imaging as part of usual care during trial duration (metformin only)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of senescent cells in adipose tissue measured by the SA-ß-GAL technique after 3 weeks of intervention, adjusted for the baseline number of senescent cells prior to the intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Senescent cell burden in adipose tissue as measured by transcriptomics using SenMayo analysis after 3 weeks of intervention, adjusted for baseline number of senescent cell burden prior to the intervention. 2. Epigenetic age (DNA methylation) after 3 weeks of intervention, adjusted for baseline epigenetic age prior to the intervention. 3. Immunosenescence as measured by IMM-AGE analysis after 3 weeks of intervention, adjusted for baseline IMM-AGE prior to the intervention. 4. Autophagic flux as measured by flow cytometry after 3 weeks of intervention, adjusted for autophagic flux prior to the intervention. 5. Nutrient sensing as measured by mTOR activation after 3 weeks of intervention, adjusted for baseline nutrient sensing prior to the intervention. 6. Mitochondrial function as measured by Seahorse after 3 weeks of intervention, adjusted for baseline mitochondrial function prior to the intervention. 7. Inflammation as measured by ELISA and multiplex technology after 3 weeks of intervention, adjusted for baseline inflammation prior to the intervention. 8. Microbial composition and functional potential of stool measured using metagenomics after 3 weeks of intervention, adjusted for baseline microbial composition and functional potential prior to the intervention. | — |
Countries
England, United Kingdom
Outcome results
None listed