Treating learning disabilities in Neurofibromatosis 1 using lamotrigine

• Register: EUCTR
• Last refreshed on: 12 July 2021
• Main ID: EUCTR2013-003405-26-DK
• Date of registration: 24/04/2017
• Prospective Registration: Yes
• Primary sponsor: Erasmus MC
• Public title: Treating learning disabilities in Neurofibromatosis 1 using lamotrigine
• Scientific title: The effect of Lamotrigine on cognitive deficits associated with Neurofibromatosis type 1: a phase II randomized controlled multi-centre trial (NF1-EXCEL) - Treating learning disabilities in Neurofibromatosis 1 using lamotrigine
• Date of first enrolment: 22/02/2018
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003405-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Denmark, Netherlands, Spain

Contacts

• Name: ENCORE - NF1 Expertise centre
• Affiliation: Erasmus MC

• Name: ENCORE - NF1 Expertise centre
• Affiliation: Erasmus MC

Key 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

Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Segmental NF1
• Hearing problems or deafness
• Use of the following medication: fenytoïn, carbamazepine, fenobarbital, primidon, rifampicine, atazanavir/ritonavir, lopinavir/ritonavir, oxcarbazepine, topiramate, oral contraceptive pill (oestrogen and progestagen) and valproic acid during the last 3 months.
• Previous use of lamotrigine
• 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neurofibromatosis type 1
MedDRA version: 20.0 Level: LLT Classification code 10029270 Term: Neurofibromatosis, type 1 (von Recklinghausen's disease) System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: Lamotrigine dispers
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: Lamotrigine
Other descriptive name: LAMOTRIGINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: lamotrigine
Other descriptive name: LAMOTRIGINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Dispersible tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The objective of this proposal is to find proof-of-principle for an effect of Lamotrigine on cognitive functioning in adolescents with Neurofibromatosis type 1.

Primary end point(s): Performal IQ (WISC-III)

Timepoint(s) of evaluation of this end point: Baseline and after 26 weeks of treatment.

Secondary Objective: Secondary objectives are the evaluation of the safety and the effect of lamotrigine on subdomains of cognitive function, intra-cortical inhibition and LTP-like plasticity.

Secondary Outcome(s)

Secondary end point(s): Visual spatial learning efficacy
- Paired Associate Learning (from the CANTAB, Cambridge Neuropsychological Test Automated Battery)
Auditory attention
- Score! (from the TEACH, Test of Everyday Attention in Children)
Fine motor coordination
- Grooved Pegboard Test
Attention problems
- Parent reported ADHD-questionnaire (AVL, ADHD Vragenlijst)
Intracortical inhibition
- Short-interval Intracortical Inhibition (SICI), measured by paired pulse stimulation
Cortical plasticity
- LTP-like plasticity, measured by paired associative stimulation (PAS)

Timepoint(s) of evaluation of this end point: Baseline and 26 weeks of treatment.

Secondary ID(s)

2013-003405-26-NL

NF1-EXCEL

Source(s) of Monetary Support

ZonMW (Governmental)

Ethics review

Status: Approved
Approval date: 22/02/2018
Contact: