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Synaptic Plasticity and Cognitive Function in RASopathies (SynCoRAS)

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ClinicalTrials.gov Identifier: NCT03504501
Recruitment Status : Recruiting
First Posted : April 20, 2018
Last Update Posted : April 18, 2019
Sponsor:
Information provided by (Responsible Party):
Technische Universität München

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.

Condition or disease Intervention/treatment Phase
Impaired Synaptic Plasticity Impaired Cognition Drug: Lovastatin Drug: Lamotrigine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders
Actual Study Start Date : March 22, 2019
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Exp. I: Noonan Syndrome - Lovastatin
200 mg Lovastatin daily for four days / Lovastatin-placebo (cross-over) prior to transcranial magnetic stimulation and test of attentional performance
Drug: Lovastatin
oral application prior to transcranial magnetic stimulation intervention

Experimental: Exp. II: Noonan Syndrome - Lamotrigine
300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance
Drug: Lamotrigine
oral application prior to transcranial magnetic stimulation intervention

Experimental: Exp. III: Neurofibromatosis Type 1 - Lamotrigine
300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance
Drug: Lamotrigine
oral application prior to transcranial magnetic stimulation intervention




Primary Outcome Measures :
  1. Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS) [ Time Frame: 12 months ]
    Changes in peak-to-peak amplitudes of motor evoked potentials (MEP)


Secondary Outcome Measures :
  1. Difference between the neuropsychological testing of attention (Test of attentional performance) after placebo and after medication (LTG and LOV) [ Time Frame: 12 months ]
    Response time (seconds) for alertness, visual scanning, Go/no Go, Incompatibility

  2. Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV) [ Time Frame: 12 months ]
    Changes in SICI


Other Outcome Measures:
  1. Assessment of safety: EMG recording during TMS evaluation [ Time Frame: 12 months ]
    Safety



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03504501


Contacts
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Contact: Volker Mall, Prof. +49 (0)89 71009-233 volker.mall@kbo.de
Contact: Nikolai Jung, Dr. +49 (0)89 71009-236 nikolai.jung@tum.de

Locations
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Germany
Technical University Munich Recruiting
Munich, Germany, 81377
Contact: Volker Mall, Prof.    +49 (0)89 71009-233    volker.mall@kbo.de   
Contact: Nikolai Jung, Dr.    +49 (0)89 71009-236    nikolai.jung@tum.de   
Sponsors and Collaborators
Technische Universität München

Publications:
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Responsible Party: Technische Universität München
ClinicalTrials.gov Identifier: NCT03504501     History of Changes
Other Study ID Numbers: SYN-1748-MAL-0030-I
2016-005022-10 ( EudraCT Number )
First Posted: April 20, 2018    Key Record Dates
Last Update Posted: April 18, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Technische Universität München:
RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation

Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Lamotrigine
Anticonvulsants
Lovastatin
L 647318
Dihydromevinolin
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Sodium Channel Blockers
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors