Safety and Tolerability of Lacosamide in Patients With Gain-of-function Nav1.7 Mutations Related Small Fiber Neuropathy

Summary

Lacosamide is a functionalized amino acid with antinociceptive properties in inflammatory and neuropathic pain, and displays a unique mechanism: it enhances slow inactivation of Nav1.3, Nav1.7, and Nav1.8. Nav1.7 is expressed predominantly in nociceptive and sympathetic neurons. Gain-of-function mutations have been described in Nav1.7 that result in extreme pain disorders such as SCN9A-associated small fiber neuropathy. In the disease states genetically linked to a gain-of-function of Nav1.7, the sodium channel is mutated to increase the sodium influx resulting in a hyperexcitable sensory neuron, and a resultant sensation of pain. The objective of the study is to determine the efficacy and safety of lacosamide, a sodium channel blocker, in patients with pain due to SCN9A-associated small fiber neuropathy.

Timeline

Start

2014-09

Primary completion

2017-05

Completion

2017-05

Publications

• Background Faber CG, Hoeijmakers JG, Ahn HS, Cheng X, Han C, Choi JS, Estacion M, Lauria G, Vanhoutte EK, Gerrits MM, Dib-Hajj S, Drenth JP, Waxman SG, Merkies IS. Gain of function Nanu1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol. 2012 Jan;71(1):26-39. doi: 10.1002/ana.22485. Epub 2011 Jun 22.
• de Greef BTA, Hoeijmakers JGJ, Geerts M, Oakes M, Church TJE, Waxman SG, Dib-Hajj SD, Faber CG, Merkies ISJ. Lacosamide in patients with Nav1.7 mutations-related small fibre neuropathy: a randomized controlled trial. Brain. 2019 Feb 1;142(2):263-275. doi: 10.1093/brain/awy329.
• de Greef BT, Merkies IS, Geerts M, Faber CG, Hoeijmakers JG. Efficacy, safety, and tolerability of lacosamide in patients with gain-of-function Nav1.7 mutation-related small fiber neuropathy: study protocol of a randomized controlled trial-the LENSS study. Trials. 2016 Jun 30;17(1):306. doi: 10.1186/s13063-016-1430-1.

Drugs

Indications