Effect of Lamotrigine on Cognition in NF1

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Neurofibromatosis type 1
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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