The purpose of this study is to determine whether lamotrigine can improve cognitive and neurophysiological deficits in adolescents with Neurofibromatosis type 1.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
41
University Hospital Leuven
Leuven, Belgium
Erasmus Medical Center
Rotterdam, South Holland, Netherlands
Hospital Sant Joan de Deu
Barcelona, Spain
Performance intelligence quotient (change from baseline)
Assessed by the Wechsler Intelligence Scales for Children - third edition (WISC-III).
Time frame: Baseline and 26 weeks
Visual-spatial working memory (change from baseline)
Assessed by the Paired Associative Learning (PAL) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Time frame: Baseline and 26 weeks
Visual perception (change from baseline)
Assessed by the Motor Free Visual Perception Test - third edition (MVPT-3).
Time frame: Baseline and 26 weeks
Sustained attention (change from baseline)
Assessed by the Sustained Attention DOTS (SA-DOTS) of the Amsterdam Neuropsychological Tasks (ANT).
Time frame: Baseline and 26 weeks
Visual-motor integration (change from baseline)
Assessed by the Beery-Buktenica Developmental Task of Visual Motor Integration - sixth edition (Beery-VMI-6).
Time frame: Baseline and 26 weeks
Fine motor coordination (change from baseline)
Assessed by the Grooved Pegboard Test.
Time frame: Baseline and 26 weeks
Attention problems (change from baseline)
Assessed by a parent rated ADHD-questionnaire, the ADHD-vragenlijst (AVL).
Time frame: Baseline, 10 weeks, 26 weeks and 52 weeks
Executive functioning (change from baseline)
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Assessed by the Behavior Rating Inventory for Executive Function parent questionnaire (BRIEF).
Time frame: Baseline, 26 weeks and 52 weeks
Short intracortical inhibition (SICI) (change from baseline)
Assessed by paired pulse transcranial magnetic stimulation (ppTMS).
Time frame: Baseline and 10 weeks
Long-term potentiation-like plasticity (change from baseline)
Assessed by paired associative stimulation (PAS) using transcranial magnetic stimulation (TMS).
Time frame: Baseline and 10 weeks