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Synaptic Plasticity and Cognitive Function in RASopathies (SynCoRAS)

Primary Purpose

Impaired Synaptic Plasticity, Impaired Cognition

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Lovastatin
Lamotrigine
Sponsored by
Technical University of Munich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Impaired Synaptic Plasticity focused on measuring RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Group 1: NS, Group 2: NF1 (both genetically assured)
  • Age >18 years
  • Signed informed consent.
  • Persons 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.
  • 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:

  • Epilepsy
  • Medication with known CNS effects
  • Severe mental retardation
  • Side effects during previous medication with and contraindications to LTG and/or LOV and/or TMS
  • Psychiatric diseases
  • Previous history of allergic reactions with LTG and LOV medications
  • Potentially unreliable patients
  • Patients who are not suitable for the study in the opinion of the investigator
  • Pregnancy (incl. positive urine pregnancy test)
  • Persons who are incapable of giving consent or do not understand the aim or rationale of the study.

Sites / Locations

  • Technical University MunichRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Exp. I: Noonan Syndrome - Lovastatin

Exp. II: Noonan Syndrome - Lamotrigine

Exp. III: Neurofibromatosis Type 1 - Lamotrigine

Arm Description

200 mg Lovastatin daily for four days / Lovastatin-placebo (cross-over) prior to transcranial magnetic stimulation and test of attentional performance

300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance

300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance

Outcomes

Primary Outcome Measures

Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS)
Changes in peak-to-peak amplitudes of motor evoked potentials (MEP)

Secondary Outcome Measures

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
Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV)
Changes in SICI

Full Information

First Posted
April 11, 2018
Last Updated
May 17, 2022
Sponsor
Technical University of Munich
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1. Study Identification

Unique Protocol Identification Number
NCT03504501
Brief Title
Synaptic Plasticity and Cognitive Function in RASopathies
Acronym
SynCoRAS
Official Title
Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2019 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Technical University of Munich

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Impaired Synaptic Plasticity, Impaired Cognition
Keywords
RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
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
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Exp. I: Noonan Syndrome - Lovastatin
Arm Type
Experimental
Arm Description
200 mg Lovastatin daily for four days / Lovastatin-placebo (cross-over) prior to transcranial magnetic stimulation and test of attentional performance
Arm Title
Exp. II: Noonan Syndrome - Lamotrigine
Arm Type
Experimental
Arm Description
300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance
Arm Title
Exp. III: Neurofibromatosis Type 1 - Lamotrigine
Arm Type
Experimental
Arm Description
300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance
Intervention Type
Drug
Intervention Name(s)
Lovastatin
Intervention Description
oral application prior to transcranial magnetic stimulation intervention
Intervention Type
Drug
Intervention Name(s)
Lamotrigine
Intervention Description
oral application prior to transcranial magnetic stimulation intervention
Primary Outcome Measure Information:
Title
Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS)
Description
Changes in peak-to-peak amplitudes of motor evoked potentials (MEP)
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Difference between the neuropsychological testing of attention (Test of attentional performance) after placebo and after medication (LTG and LOV)
Description
Response time (seconds) for alertness, visual scanning, Go/no Go, Incompatibility
Time Frame
12 months
Title
Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV)
Description
Changes in SICI
Time Frame
12 months
Other Pre-specified Outcome Measures:
Title
Assessment of safety: EMG recording during TMS evaluation
Description
Safety
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Group 1: NS, Group 2: NF1 (both genetically assured) Age >18 years Signed informed consent. Persons 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. 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: Epilepsy Medication with known CNS effects Severe mental retardation Side effects during previous medication with and contraindications to LTG and/or LOV and/or TMS Psychiatric diseases Previous history of allergic reactions with LTG and LOV medications Potentially unreliable patients Patients who are not suitable for the study in the opinion of the investigator Pregnancy (incl. positive urine pregnancy test) Persons who are incapable of giving consent or do not understand the aim or rationale of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Volker Mall, Prof.
Phone
+49 (0)89 71009-233
Email
volker.mall@kbo.de
First Name & Middle Initial & Last Name or Official Title & Degree
Nikolai Jung, Dr.
Phone
+49 (0)89 71009-236
Email
nikolai.jung@tum.de
Facility Information:
Facility Name
Technical University Munich
City
Munich
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Volker Mall, Prof.
Phone
+49 (0)89 71009-233
Email
volker.mall@kbo.de
First Name & Middle Initial & Last Name & Degree
Nikolai Jung, Dr.
Phone
+49 (0)89 71009-236
Email
nikolai.jung@tum.de

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24088225
Citation
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.
Results Reference
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Synaptic Plasticity and Cognitive Function in RASopathies

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