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Neurofibromatosis Type 1Phase 2/3NF1-EXCELNCT02256124

Effect of Lamotrigine on Cognition in NF1

A Phase 2/3 study testing Lamotrigine in people with Neurofibromatosis Type 1, run by Erasmus Medical Center at 3 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 12 to 18 years
Conditions the study is for
Neurofibromatosis Type 1
What is being tested?
Lamotrigine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
41 participants
Where
3 sitesin 3 countries
Study dates
Oct 2014to Apr 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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 locations and contacts

3 sites in 3 countries.

3 sites in 3 countries

Belgium1 site

  • University Hospital Leuven

    Leuven, B-3000

Other trials in Belgium

Netherlands1 site

  • Erasmus Medical Center

    Rotterdam, South Holland, 3015CN

Other trials in Netherlands

Spain1 site

  • Hospital Sant Joan de Deu

    Barcelona

Other trials in Spain

About this study

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

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

Read the 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.

Being tested
Lamotrigine, Placebo
Keywords
Neurofibromatosis type 1, NF1, Cognition, Learning problems, Lamotrigine, Transcranial magnetic stimulation, TMS
Medical subject headings
Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LamotrigineDrug

    Also called Lamictal

  • PlaceboDrug

Study groups in NCT02256124
Study groupRoleWhat they receive
LamotrigineExperimentalLamotrigine 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.
Receives: Drug: Lamotrigine
PlaceboPlacebo comparatorPlacebo tablets during 28 consecutive weeks, with identical appearance to lamotrigine tablets, mimicking the lamotrigine dosing schedule.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Performance intelligence quotient (change from baseline)

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

    Measured: Baseline and 26 weeks

Secondary outcomes (9)

  1. Visual-spatial working memory (change from baseline)

    Assessed by the Paired Associative Learning (PAL) task of the Cambridge Neuropsychological Test Automated Battery (CANTAB).

    Measured: Baseline and 26 weeks

  2. Visual perception (change from baseline)

    Assessed by the Motor Free Visual Perception Test - third edition (MVPT-3).

    Measured: Baseline and 26 weeks

  3. Sustained attention (change from baseline)

    Assessed by the Sustained Attention DOTS (SA-DOTS) of the Amsterdam Neuropsychological Tasks (ANT).

    Measured: Baseline and 26 weeks

  4. Visual-motor integration (change from baseline)

    Assessed by the Beery-Buktenica Developmental Task of Visual Motor Integration - sixth edition (Beery-VMI-6).

    Measured: Baseline and 26 weeks

  5. Fine motor coordination (change from baseline)

    Assessed by the Grooved Pegboard Test.

    Measured: Baseline and 26 weeks

  6. Attention problems (change from baseline)

    Assessed by a parent rated ADHD-questionnaire, the ADHD-vragenlijst (AVL).

    Measured: Baseline, 10 weeks, 26 weeks and 52 weeks

  7. Executive functioning (change from baseline)

    Assessed by the Behavior Rating Inventory for Executive Function parent questionnaire (BRIEF).

    Measured: Baseline, 26 weeks and 52 weeks

  8. Short intracortical inhibition (SICI) (change from baseline)

    Assessed by paired pulse transcranial magnetic stimulation (ppTMS).

    Measured: Baseline and 10 weeks

  9. Long-term potentiation-like plasticity (change from baseline)

    Assessed by paired associative stimulation (PAS) using transcranial magnetic stimulation (TMS).

    Measured: Baseline and 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2014 (estimated)
  2. Study startOct 2014
  3. Primary completionApr 2020
  4. Study completionApr 2020

Why it stopped: Due to our experience, the small number of new inclusions, and the uncertainty regarding the COVID-19 outbreak, we have decided to discontinue the study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02256124
Sponsor's protocol ID
MEC-2013-460
Other IDs
2013-003405-26, NL 44912.078.13, 113303003
Acronym
NF1-EXCEL
Status last verified
Apr 2020
First submitted
17 Sep 2014
Last updated
14 Apr 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Ottenhoff MJ, Heuvelmans A, Castricum J, Tulen JH, Rens G, Fujiyama H, Levin O, Swinnen SP, Moll HA, Wit MY, Elgersma Y. The effect of lamotrigine on cortical inhibition and plasticity in Neurofibromatosis type 1: Exploratory analysis of a randomized controlled trial (NF1-EXCEL). Clin Neurophysiol. 2025 May;173:150-162. doi: 10.1016/j.clinph.2025.02.270. Epub 2025 Mar 10.

    PubMed 40121838

  • Ottenhoff MJ, Mous SE, Castricum J, Rietman AB, Oostenbrink R, van der Vaart T, Tulen JHM, Parra A, Ramos FJ, Legius E, Moll HA, Elgersma Y, de Wit MY; ENCORE Expertise Center for NF1. Lamotrigine for cognitive deficits associated with neurofibromatosis type 1: A phase II randomized placebo-controlled trial. Dev Med Child Neurol. 2025 Apr;67(4):537-549. doi: 10.1111/dmcn.16094. Epub 2024 Sep 28.

    PubMed 39340758

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Lamotrigine in people with Neurofibromatosis Type 1, run by Erasmus Medical Center at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Belgium, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to our experience, the small number of new inclusions, and the uncertainty regarding the COVID-19 outbreak, we have decided to discontinue the study.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Performance intelligence quotient (change from baseline) (time frame: Baseline and 26 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02256124, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2020; AzTrials last refreshed its copy on 7 Nov 2026.

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