Clinical Trial: Effect of Lamotrigine on Cognition in NF1

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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

Detailed Summary: 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.
Sponsor: Erasmus Medical Center

Current Primary Outcome: Performance intelligence quotient (change from baseline) [ Time Frame: Baseline and 26 weeks ]

Assessed by the Wechsler Intelligence Scales for Children - third edition (WISC-III).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Visual-spatial working memory (change from baseline) [ Time Frame: Baseline and 26 weeks ]
    Assessed by the Paired Associative Learning (PAL) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB).
  • Visual perception (change from baseline) [ Time Frame: Baseline and 26 weeks ]
    Assessed by the Motor Free Visual Perception Test - third edition (MVPT-3).
  • Sustained attention (change from baseline) [ Time Frame: Baseline and 26 weeks ]
    Assessed by the Sustained Attention DOTS (SA-DOTS) of the Amsterdam Neuropsychological Tasks (ANT).
  • Visual-motor integration (change from baseline) [ Time Frame: Baseline and 26 weeks ]
    Assessed by the Beery-Buktenica Developmental Task of Visual Motor Integration - sixth edition (Beery-VMI-6).
  • Fine motor coordination (change from baseline) [ Time Frame: Baseline and 26 weeks ]
    Assessed by the Grooved Pegboard Test.
  • Attention problems (change from baseline) [ Time Frame: Baseline, 10 weeks, 26 weeks and 52 weeks ]
    Assessed by a parent rated ADHD-questionnaire, the ADHD-vragenlijst (AVL).
  • Executive functioning (change from baseline) [ Time Frame: Baseline, 26 weeks and 52 weeks ]
    Assessed by the Behavior Rating Inventory for Executive Function parent questionnaire (BRIEF).
  • Short intracortical inhibition (SICI) (change from baseline) [ Time Frame: Baseline and 10 weeks ]
    Assessed by paired pulse transcranial magnetic stimulation (ppTMS).
  • Long-term potentiation-like plasticity (change from baseline) [ Time Frame: Baseline and 10 weeks ]
    Assessed by paired associative stimulation (PAS) using transcranial magnetic stimulation (TMS).


Original Secondary Outcome: Same as current

Information By: Erasmus Medical Center

Dates:
Date Received: September 17, 2014
Date Started: October 2014
Date Completion: September 2016
Last Updated: December 8, 2015
Last Verified: December 2015