NCT02256124

Effect of Lamotrigine on Cognition in NF1

The Effect of Lamotrigine on Cognitive Deficits Associated With Neurofibromatosis Type 1: a Phase II Randomized Controlled Multi-centre Trial (NF1-EXCEL)

• Status: Terminated
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Erasmus Medical Center · Academic / Other
• Sex: All
• Age: 12 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether lamotrigine can improve cognitive and neurophysiological deficits in adolescents with Neurofibromatosis type 1.

Detailed description

Cognitive deficits in the autosomal dominant disorder Neurofibromatosis type 1 (NF1) typically consist of a lower than average IQ, impaired visual-spatial learning, attention problems and impaired executive functioning. These deficits have a substantial influence on the daily life of pediatric and adolescent individuals with NF1. One of the key underlying mechanisms of these deficits is an increased gamma-aminobutyric acid (GABA)-ergic inhibition and a subsequent decrease in synaptic plasticity. The ENCORE laboratory has recently shown that loss of the NF1-gene is associated with attenuated function of the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1). These channels, enriched in membranes of inhibitory interneurons, play an important role in the pathophysiology underlying the cognitive deficits in NF1. Lamotrigine, an HCN-agonist, restored function of HCN1, together with the electrophysiological and visual-spatial learning deficits in Nf1-mice. Thus, lamotrigine is a novel candidate drug for treating cognitive deficits associated with NF1.

Conditions

• Neurofibromatosis Type 1

Interventions

Type	Name	Description
DRUG	Lamotrigine
DRUG	Placebo

Timeline

• Start date: 2014-10-01
• Primary completion: 2020-04-01
• Completion: 2020-04-01
• First posted: 2014-10-03
• Last updated: 2020-04-14

Locations

3 sites across 3 countries: Belgium, Netherlands, Spain