Phase III randomized double-blind placebo-controlled trial of metformin for cognitive recovery and white matter growth in paediatric medulloblastoma patients

A critical barrier to improving the quality of life of children/adolescents living with cancer is that our curative therapies have toxic effects on healthy tissue, which result in long term problems. This is no truer than for children and adolescents who survive medulloblastoma: they experience brain injury and cognitive impairment. There are few therapies for restoring cognitive function and promoting brain growth in survivors; however exciting new work in regenerative medicine offers hope. We may be able to help repair the brain following injury using brain stem cells - special cells capable of producing new neurons and glia cells. The drug metformin can promote rescue of cognition and brain growth in animal models by activating stem cells in the brain. We have found that this drug is safe and feasible to use in children treated for a brain tumour and has potential to improve thinking and brain growth. We now seek to find out if this is true in a large national clinical trial. We will conduct a clinical trial at 8 paediatric cancer program across Canada to test the efficacy of metformin treatment for cognitive recovery in children and adolescents treated for medulloblastoma - a brain tumour that requires aggressive therapy leaving survivors with learning problems. The trial will be conducted with 70 children and adolescents. Participants will be randomly assigned to take metformin or a placebo. We will use tests of thinking and learning and brain scans as outcomes. As survival rates for brain tumours increase, it is important that in caring for children we not only work to cure their cancer, but also to reduce the long term negative effects. If we find that metformin improves thinking and brain growth in paediatric survivors of medulloblastoma, then this may offer a viable therapeutic approach that may significantly improve the quality of life of these vulnerable patients - and provide a model for treatment of long term effects in other paediatric cancers. Through our work we seek to offer new hope to children and their families who suffer from the long term problems caused by paediatric cancer. CIHR partnership: $1,077,131