Synaptic Plasticity and Cognitive Function in RASopathies

Impaired Cognition Clinical Trial

— SynCoRAS  

Official title:

Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03504501
• Other study ID #: SYN-1748-MAL-0030-I
• Secondary ID: 2016-005022-10
• Status: Terminated
• Phase: Phase 2
• Start date: March 22, 2019
• Est. completion date: October 31, 2023

Study information

• Verified date: May 2023
• Source: Technical University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: October 31, 2023
• Est. primary completion date: February 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Impaired Cognition
• Impaired Synaptic Plasticity

Intervention

Drug:
• Lovastatin
oral application prior to transcranial magnetic stimulation intervention
• Lamotrigine
oral application prior to transcranial magnetic stimulation intervention

Locations

Country	Name	City	State
Germany	Technical University Munich	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Technical University of Munich

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Mainberger F, Jung NH, Zenker M, Wahllander U, Freudenberg L, Langer S, Berweck S, Winkler T, Straube A, Heinen F, Granstrom S, Mautner VF, Lidzba K, Mall V. Lovastatin improves impaired synaptic plasticity and phasic alertness in patients with neurofibromatosis type 1. BMC Neurol. 2013 Oct 2;13:131. doi: 10.1186/1471-2377-13-131. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of safety: EMG recording during TMS evaluation	Safety	12 months
Primary	Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS)	Changes in peak-to-peak amplitudes of motor evoked potentials (MEP)	12 months
Secondary	Difference between the neuropsychological testing of attention (Test of attentional performance) after placebo and after medication (LTG and LOV)	Response time (seconds) for alertness, visual scanning, Go/no Go, Incompatibility	12 months
Secondary	Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV)	Changes in SICI	12 months