Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex

Summary

There had been much evidence in aspirin controlling tumorous conditions conducted by basic researches, especially through mammilian target of rapamycin (mTOR) pathway. The investigator observed efficacy of aspirin in the treatment of tuberous sclerosis complex (TSC) in one child who got Kawasaki disease and in the addition four TSC patients with epilepsy. The investigator intend to evaluate whether aspirin would be an effective add-on treatment in TSC patients with refractory seizures.

Timeline

Start

2017-11-20

Primary completion

2021-11-20

Completion

2021-11-20

Publications

• Background Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006 Mar;59(3):490-8. doi: 10.1002/ana.20784.
• Background Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4;363(19):1801-11. doi: 10.1056/NEJMoa1001671.
• Background Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG. Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012 Jun;142(7):1504-15.e3. doi: 10.1053/j.gastro.2012.02.050. Epub 2012 Mar 6.
• Background Chen CT, Du Y, Yamaguchi H, Hsu JM, Kuo HP, Hortobagyi GN, Hung MC. Targeting the IKKbeta/mTOR/VEGF signaling pathway as a potential therapeutic strategy for obesity-related breast cancer. Mol Cancer Ther. 2012 Oct;11(10):2212-21. doi: 10.1158/1535-7163.MCT-12-0180. Epub 2012 Jul 23.
• Background Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. doi: 10.1016/j.pediatrneurol.2013.08.001.
• Background Overwater IE, Rietman AB, Bindels-de Heus K, Looman CW, Rizopoulos D, Sibindi TM, Cherian PJ, Jansen FE, Moll HA, Elgersma Y, de Wit MC. Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized controlled trial. Neurology. 2016 Sep 6;87(10):1011-8. doi: 10.1212/WNL.0000000000003077. Epub 2016 Aug 10.

Drugs

Indications