Brief Title
Effect of Lamotrigine on Cognition in NF1
Official Title
The Effect of Lamotrigine on Cognitive Deficits Associated With Neurofibromatosis Type 1: a Phase II Randomized Controlled Multi-centre Trial (NF1-EXCEL)
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 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.
Study Phase
Phase 2/Phase 3
Study Type
Interventional
Primary Outcome
Performance intelligence quotient (change from baseline)
Secondary Outcome
Visual-spatial working memory (change from baseline)
Condition
Neurofibromatosis Type 1
Intervention
Lamotrigine
Study Arms / Comparison Groups
Lamotrigine
Description: Lamotrigine during 28 consecutive weeks: 8 weeks dose-increase phase: from 25mg once daily to 100mg twice daily 18 weeks target-dose phase: 100mg twice daily 2 weeks decline-phase: 100mg once daily.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
41
Start Date
October 2014
Completion Date
April 2020
Primary Completion Date
April 2020
Eligibility Criteria
Inclusion Criteria: - NF1 patients with a genetically confirmed diagnosis - Age 12-17.5 years at inclusion - Oral and written informed consent by parents and assent from participants Exclusion Criteria: - Segmental NF1 - Severe hearing problems or deafness - Severe visual problems or blindness - Use of the following medication, as of interaction with lamotrigine: phenytoin, carbamazepine, phenobarbital, primidon, rifampicin, atazanavir/ritonavir, lopinavir/ritonavir, oxcarbazepine, topiramate, oral contraceptive pill including stop-week (estrogen and progesterone) and valproic acid during 3 months before inclusion. - Use of psycho-active medication other than methylphenidate - Previous allergic reactions to anti-epileptic drugs - Epilepsy or epilepsy in the past - Suicidal thoughts or behaviour - Renal insufficiency - Liver insufficiency - Pregnancy - Brain tumour or other brain pathology potentially influencing the outcome measures
Gender
All
Ages
12 Years - 18 Years
Accepts Healthy Volunteers
No
Contacts
Ype Elgersma, PhD, ,
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT02256124
Organization ID
MEC-2013-460
Secondary IDs
2013-003405-26
Responsible Party
Principal Investigator
Study Sponsor
Erasmus Medical Center
Collaborators
Universitaire Ziekenhuizen Leuven
Study Sponsor
Ype Elgersma, PhD, Principal Investigator, Erasmus Medical Center
Verification Date
April 2020