Effect of Lamotrigine on Cognition in NF1

Study Purpose

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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	12 Years - 18 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02256124
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2/Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Erasmus Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Ype Elgersma, PhDHenriette A Moll, MD, PhD
Principal Investigator Affiliation	Erasmus Medical CenterErasmus Medical Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Belgium, Netherlands, Spain
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Neurofibromatosis Type 1

Additional Details

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.

Arms & Interventions

Arms

Experimental: Lamotrigine

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.

Placebo Comparator: Placebo

Placebo tablets during 28 consecutive weeks, with identical appearance to lamotrigine tablets, mimicking the lamotrigine dosing schedule.

Interventions

Drug: - Lamotrigine

Drug: - Placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

University Hospital Leuven, Leuven, Belgium

Status

Recruiting

Address

University Hospital Leuven

Leuven, , B-3000

Site Contact

Eric Legius, MD, PhD

[email protected]

+3216345903

Erasmus Medical Center, Rotterdam, South Holland, Netherlands

Status

Recruiting

Address

Erasmus Medical Center

Rotterdam, South Holland, 3015CN

Site Contact

[email protected]

+31107036956

Hospital Sant Joan de Deu, Barcelona, Spain

Status

Recruiting

Address

Hospital Sant Joan de Deu

Barcelona, ,

Site Contact

Hector Salvador Hernandez, Dr.

[email protected]

+31107036956

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