Effect of Lamotrigine on Cognition in NF1

NCT02256124 | Terminated Phase 2 DMC

• 4 other identifiers: MEC-2013-4602013-003405-26NL 44912.078.13113303003
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 3

Brief Summary

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

Conditions

Neurofibromatosis Type 1

Keywords

Neurofibromatosis type 1; NF1; Cognition; Learning problems; Lamotrigine; Transcranial magnetic stimulation; TMS

Outcome Measures

Primary Outcomes (1)

• Performance intelligence quotient (change from baseline)

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

  Baseline and 26 weeks

Secondary Outcomes (9)

• Visual-spatial working memory (change from baseline)

  Baseline and 26 weeks

• Visual perception (change from baseline)

  Baseline and 26 weeks

• Sustained attention (change from baseline)

  Baseline and 26 weeks

• Visual-motor integration (change from baseline)

  Baseline and 26 weeks

• Fine motor coordination (change from baseline)

  Baseline and 26 weeks

Other Outcomes (11)

• Full IQ (Intelligence Quotient)

  Baseline

• Adverse event registration

  Baseline, 4 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, 26 weeks, 28 weeks and additionally on indication

• NF1 disease severity

  Baseline

Study Arms (2)

Lamotrigine

EXPERIMENTAL

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.

Drug: Lamotrigine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Lamotrigine DRUG

Also known as: Lamictal

Lamotrigine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• NF1 patients with a genetically confirmed diagnosis
• Oral and written informed consent by parents and assent from participants

You may not qualify if:

• Segmental NF1
• Severe hearing problems or deafness
• Severe visual problems or blindness
• 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

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator
• Hospital Sant Joan de Deu: collaborator

Study Sites (3)

University Hospital Leuven

Leuven, B-3000, Belgium

Location

Erasmus Medical Center

Rotterdam, South Holland, 3015CN, Netherlands

Location

Hospital Sant Joan de Deu

Barcelona, Spain

Location

Related Publications (2)

• 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.

  PMID: 40121838 DERIVED

• 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.

  PMID: 39340758 DERIVED

Related Links

• ENCORE expertise center

MeSH Terms

Conditions

Neurofibromatosis 1

Interventions

Lamotrigine

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Triazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ype Elgersma, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Henriette A Moll, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSc

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: October 3, 2014
• Study Start: October 1, 2014
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: April 14, 2020

Record last verified: 2020-04

Locations

NL (1); BE (1); ES (1)