Impaired Cognition, Impaired Synaptic Plasticity
Conditions
Keywords
RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation
Brief summary
The project is targeting cognitive impairment, one of the main health problems of patients with RAS pathway disorders. The aim of this study is to translate findings of animal studies to humans. This has been done by the applicants successfully for Lovastatin in Nf1. This result will be transferred to patients with Noonan Syndrome. lamotrigine is most likely a more effective and promising substance improving synaptic plasticity and consecutive cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness and changes in alertness may be a precondition for improvement of cognition.
Interventions
DRUGLovastatin
oral application prior to transcranial magnetic stimulation intervention
DRUGLamotrigine
oral application prior to transcranial magnetic stimulation intervention
Sponsors
Technical University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Monocenter, randomized, double-blind, parallel-group, placebo controlled, cross-over design with a series of three experiments (Noonan Syndrome: 2 experiments; Neurofibromatosis type 1 1 experiment) and n=14 participants per experiments
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Group 1: NS, Group 2: NF1 (both genetically assured) 2. Age ≥16 years 3. The adolescent (≥16) and legal guardian who are capable to give their consent and understand the aim and rationale of the study. In case of doubts, an independent medical practitioner will evaluate the capacity to consent. 4. Signed informed consent if ≥ 16 years and legal guardian. 5. Persons who are ≥ 18 years old and capable to give their consent and understand the aim and rationale of the study. In case of doubts, an independent medical practitioner will evaluate the capacity to consent. 6. Signed informed consent if ≥ 18 years. 7. Male participants and female participants who are not capable of bearing children or who use a method of contraception that is medically approved by the health authority of the respective country.
Exclusion criteria
1. Epilepsy 2. Medication with known CNS effects 3. Severe mental retardation 4. Side effects during previous medication with and contraindications for LTG and/or LOV and/or TMS 5. Psychiatric diseases 6. Previous history of allergic reactions with LTG and LOV medications 7. Potentially unreliable patients 8. Patients who are not suitable for the study in the opinion of the investigator 9. Pregnancy (incl. positive urine pregnancy test) 10. Persons who are incapable of giving consent or do not understand the aim or rationale of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS) | 12 months | Changes in peak-to-peak amplitudes of motor evoked potentials (MEP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference between the neuropsychological testing of attention (Test of attentional performance) after placebo and after medication (LTG and LOV) | 12 months | Response time (seconds) for alertness, visual scanning, Go/no Go, Incompatibility |
| Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV) | 12 months | Changes in SICI |
Other
| Measure | Time frame | Description |
|---|---|---|
| Assessment of safety: EMG recording during TMS evaluation | 12 months | Safety |
Countries
Germany
Outcome results
None listed