Impaired Synaptic PlasticityPhase 2SynCoRASNCT03504501
Synaptic Plasticity and Cognitive Function in RASopathies
A Phase 2 study testing Lovastatin and Lamotrigine in people with Impaired Synaptic Plasticity and Impaired Cognition, run by Technical University of Munich at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Impaired Synaptic Plasticity, Impaired Cognition
- What is being tested?
- Lovastatin and Lamotrigine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- 22 Mar 2019to 31 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Group 1: NS, Group 2: NF1 (both genetically assured)
- Age ≥16 years
- 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.
- Signed informed consent if ≥ 16 years and legal guardian.
- 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.
- Signed informed consent if ≥ 18 years.
- 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.
Who cannot join
- Epilepsy
- Medication with known CNS effects
- Severe mental retardation
- Side effects during previous medication with and contraindications for LTG and/or LOV and/or TMS
- Psychiatric diseases
- Previous history of allergic reactions with LTG and LOV medications
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders
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.
- Conditions
- Impaired Synaptic Plasticity, Impaired Cognition
- Being tested
- Lovastatin, Lamotrigine
- Keywords
- RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation
- Medical subject headings
- Cognition Disorders, Neurofibromatosis 1, Noonan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LovastatinDrug
oral application prior to transcranial magnetic stimulation intervention
LamotrigineDrug
oral application prior to transcranial magnetic stimulation intervention
| Study group | Role | What they receive |
|---|---|---|
| Exp. I: Noonan Syndrome - Lovastatin | Experimental | 200 mg Lovastatin daily for four days / Lovastatin-placebo (cross-over) prior to transcranial magnetic stimulation and test of attentional performance Receives: Drug: Lovastatin |
| Exp. II: Noonan Syndrome - Lamotrigine | Experimental | 300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance Receives: Drug: Lamotrigine |
| Exp. III: Neurofibromatosis Type 1 - Lamotrigine | Experimental | 300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance Receives: Drug: Lamotrigine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS)
Changes in peak-to-peak amplitudes of motor evoked potentials (MEP)
Measured: 12 months
Secondary outcomes (2)
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
Measured: 12 months
Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV)
Changes in SICI
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start22 Mar 2019
- Primary completion9 Feb 2023
- Study completion31 Oct 2023
Why it stopped: The study has been terminated prematurely due to recruitment difficulties. Current status: recruitment stopped and cleaning of the database is ongoing.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Impaired Synaptic PlasticityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504501
- Sponsor's protocol ID
- SYN-1748-MAL-0030-I
- Other IDs
- 2016-005022-10, 2016
- Acronym
- SynCoRAS
- Status last verified
- May 2023
- First submitted
- 11 Apr 2018
- Last updated
- 30 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 24088225Jung NH, Egert-Schwender S, Schossow B, Kehl V, Wahllander U, Brich L, Janke V, Blankenstein C, Zenker M, Mall V. Improvement of synaptic plasticity and cognitive function in RASopathies-a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS). Trials. 2023 Jun 6;24(1):383. doi: 10.1186/s13063-023-07392-z.
PubMed 37280688
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improvement of Synaptic Plasticity and Cognitive Function in RAS Pathway Disorders
- ClinicalTrials.gov ID
- NCT03504501
- Acronym / sponsor ID
- SynCoRAS / SYN-1748-MAL-0030-I
- Conditions
- Impaired Synaptic Plasticity, Impaired Cognition
- Keywords
- RASopathies, neurofibromatosis type 1, noonan syndrome, synaptic plasticity, transcranial magnetic stimulation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study has been terminated prematurely due to recruitment difficulties. Current status: recruitment stopped and cleaning of the database is ongoing.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Study start
- 22 Mar 2019 (actual)
- Primary completion
- 9 Feb 2023 (actual)
- Study completion
- 31 Oct 2023 (actual)
- First posted
- 20 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- 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
| Arm | Type | Receives |
|---|---|---|
| Exp. I: Noonan Syndrome - Lovastatin | Experimental | Drug: Lovastatin200 mg Lovastatin daily for four days / Lovastatin-placebo (cross-over) prior to transcranial magnetic stimulation and test of attentional performance |
| Exp. II: Noonan Syndrome - Lamotrigine | Experimental | Drug: Lamotrigine300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance |
| Exp. III: Neurofibromatosis Type 1 - Lamotrigine | Experimental | Drug: Lamotrigine300 mg Lamotrigine single dose / Lamotrigine-placebo prior to transcranial magnetic stimulation and test of attentional performance |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Group 1: NS, Group 2: NF1 (both genetically assured)
- Age ≥16 years
- 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.
- Signed informed consent if ≥ 16 years and legal guardian.
- 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.
Key exclusion criteria (10 listed)
- Epilepsy
- Medication with known CNS effects
- Severe mental retardation
- Side effects during previous medication with and contraindications for LTG and/or LOV and/or TMS
- Psychiatric diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lovastatinoral application prior to transcranial magnetic stimulation intervention | Drug | Exp. I: Noonan Syndrome - Lovastatin |
| Lamotrigineoral application prior to transcranial magnetic stimulation intervention | Drug | Exp. II: Noonan Syndrome - Lamotrigine, Exp. III: Neurofibromatosis Type 1 - Lamotrigine |
Primary outcome
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)
2 secondary outcomes
Difference between the neuropsychological testing of attention (Test of attentional performance) after placebo and after medication (LTG and LOV)
Time frame: 12 months
Differences in short interval cortical inhibition (SICI) after placebo and after medication (LTG and LOV)
Time frame: 12 months
Results and safety
The study was stopped early (reason given: The study has been terminated prematurely due to recruitment difficulties. Current status: recruitment stopped and cleaning of the database is ongoing.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2023.
- Background: PubMed 24088225Mainberger 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.
- Derived from this study: PubMed 37280688Jung NH, Egert-Schwender S, Schossow B, Kehl V, Wahllander U, Brich L, Janke V, Blankenstein C, Zenker M, Mall V. Improvement of synaptic plasticity and cognitive function in RASopathies-a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS). Trials. 2023 Jun 6;24(1):383. doi: 10.1186/s13063-023-07392-z.
- Individual participant dataSharing planned: No
Related trials for Impaired Synaptic Plasticity
Recruiting
Epigenetic Enhancement of Cognitive Training in Aging Mood and Schizophrenia Spectrum Disorder Populations
Bipolar Disorder (BD), Depression - Major Depressive Disorder
Recruiting
Improving Neurological Health With Acetylcholine Via Neuroplasticity-based Computerized Exercise in Mild Cognitive Impairment
Mild Cognitive Impairment
Recruiting
Accelerated Age-related Cognitive Decline: Impact of Exercise on Executive Function and Neuroplasticity
Mild Cognitive Impairment, Chronic Kidney Diseases
Recruiting
Effects of High-Frequency rTMS on Cortical Motor Mapping in Stroke Patients With Severe Upper Limb Impairment (MAP2024SJD)
Stroke, Upper Limb Paresis
Recruiting
Interventions in Mathematics and Cognitive Skills
Math Learning Disability, Child Development
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lovastatin and Lamotrigine in people with Impaired Synaptic Plasticity and Impaired Cognition, run by Technical University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study has been terminated prematurely due to recruitment difficulties. Current status: recruitment stopped and cleaning of the database is ongoing.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Long-term potentiation (LTP)-like plasticity measured with transcranial magnetic stimulation (TMS) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03504501, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2023.