MiTS is a randomized, double-blind, parallel group, placebo-controlled trial of metformin in tuberous sclerosis complex. The trial is run by researchers based at Bristol Royal Hospital for Children, led by Professor Finbar O’Callaghan.
Tuberous sclerosis complex (TSC) is a genetic disorder characterised by the development of benign tumours (hamartomas) throughout the body. Problems associated with this condition include epilepsy, learning and behavioural difficulties, disfiguring facial tumours, bleeding from kidney tumours, and the blockage of fluids in ventricles in the brain. Kidney and brain tumours can be life-threatening. Current treatment is aimed at managing these problems but there is no therapy that modifies the progression of TSC. The drug metformin could reduce the growth of tumours in TSC, by regulating a pathway within each cell that promotes cell growth. It is the loss of regulation of this pathway that causes tumour growth in TSC. Metformin is a safe drug used since the 1950s by millions of people worldwide with diabetes. It rarely has serious side-effects. This research will test if metformin is effective at reducing the size of tumours in people with TSC. The study will last 18 months and aims to recruit 100 people with TSC. Half will take metformin and half will take a placebo (a dummy drug) for 12 months. All will have MRI scans at the start and 12 months to measure their kidney and brain tumour size. They will also have assessments of their facial and nail tumours, epilepsy, cognition and quality of life. Their blood sugar and kidney and liver function will be monitored during the study. If metformin safely reduces tumour size, or slows growth of tumours, it will benefit people with TSC. They should have less pain, sickness, disfigurement, need less surgery, and be at lower risk of dangerous bleeding from tumours. Metformin would be more effective than standard care and significantly cheaper for the NHS.