A cheap, widely available diabetes drug is being tested as a treatment for epilepsy that resists standard medications in people with the genetic condition tuberous sclerosis complex (TSC). Around two-thirds of people with TSC have seizures that current drugs cannot control. The condition causes overactivity of a cell-growth regulator called mTOR, leading to benign tumours in the brain, skin, and kidneys, as well as epilepsy. Existing mTOR inhibitors like everolimus are effective but expensive and carry serious side effects. Metformin, used since the 1950s for diabetes, also inhibits mTOR but costs pennies per dose and has a well-established safety profile. This trial will recruit 136 patients aged 6–65 with drug-resistant TSC-related epilepsy. Half will receive metformin, half a placebo, for 12 months alongside their usual care. Researchers will measure changes in seizure frequency, tumour volume, and quality of life, sleep, and behaviour. If metformin proves effective, it could replace far more expensive drugs and invasive procedures like epilepsy surgery, shifting clinical practice and commissioning pathways. Because it is safe and inexpensive, the impact on patients’ daily lives—and on the natural history of TSC itself—could be substantial.
View original technical description
Research question Does adjunctive metformin reduce seizure frequency in patients with Tuberous Sclerosis Complex (TSC)-related drug-resistant epilepsy? Background TSC is a genetic disease affecting approximately 8-9 per 100,000 of the population. Up to 90% of affected individuals have epileptic seizures and almost two thirds of patients have seizures that are not controlled with currently available anti-seizure medications. The underlying problem in patients with TSC is a failure to control the growth and proliferation of cells throughout the body. Specifically, there is a failure to control the activity of a molecule in cells that is called "the mechanistic target of rapamycin (mTOR)". Overactivity of mTOR results in the formation of benign tumours throughout the body, most commonly in the brain, skin and kidneys. It also causes epilepsy. Drugs that inhibit the activity of mTOR have been shown to reduce the size of the tumours and reduce the frequency of seizures in TSC. Everolimus is a mTOR inhibitor licensed for patients with TSC. It is expensive and has significant side-effects, including mortality. Metformin is a diabetic drug that has been used widely since the 1950s and is also an mTOR inhibitor. It is inexpensive and it has a very good side-effect profile. If proven to be effective, metformin could be used for epilepsy treatment ahead of Everolimus, other high-cost drugs and invasive interventions such as epilepsy surgery. Aims and objectives This study aims to assess the efficacy of adjunctive metformin on epilepsy in TSC. Study objectives include assessing the effect of metformin on seizure frequency, volume of SEGA’s and AML’s, and quality of life, sleep and behaviour. Methods This is a national multicentre double-blind placebo-controlled randomised trial. Patients aged 6-65 years with a diagnosis of TSC-related drug-resistant epilepsy will be recruited. They will have an eight-week baseline assessment of their seizure frequency using seizure diaries. 136 randomised patients will receive either metformin or placebo for 12 months. Patients will also continue with usual clinical care. Seizure frequency will be re-assessed between months 4 and 6, and months 10 and 12. Efficacy will be assessed by comparing seizure frequency between metformin and placebo groups, adjusting for baseline frequency. Quality of life, sleep quality and behaviour will be assessed at baseline and 12 months. As per UK guidelines, some patients require yearly brain and Kidney MRI scans as part of their routine TSC care. Some patients require general anaesthetic for scans. Where possible, SEGA and AML volumes will be calculated from routine brain and kidney MRI scans taken before randomisation and following end of trial treatment at 12 months. Timelines for delivery Study duration is 50 months: 9-month set-up; 20 months recruitment/randomisation period, including internal pilot; 15 months post-randomisation follow-up; 6 months analysis and dissemination. Anticipated impact and dissemination Study results will be published in scientific journals and presented to patients and their families in public meetings. All patients who take part will be sent newsletters and regular updates. Given that metformin is inexpensive and safe, if found to be effective it is likely to change clinical practice and commissioning pathways, having a significant impact on patients and potentially altering the natural history of TSC.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know