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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 3 November 2020
Main ID:  EUCTR2016-005022-10-DE
Date of registration: 09/11/2017
Prospective Registration: Yes
Primary sponsor: Technische Universität München, Fakultät für Medizin
Public title: Improvement of synaptic plasticity and cognitive function in RAS pathway disorders
Scientific title: Improvement of synaptic plasticity and cognitive function in RAS pathway disorders
Date of first enrolment: 13/02/2018
Target sample size: 30
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-005022-10
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes
Randomised: yes
Open: no
Single blind: no
Double blind: yes
Parallel group: yes
Cross over: yes
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: yes
Other: no
Number of treatment arms in the trial: 2
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Germany
Contacts
Name: Lehrstuhl für Sozialpädiatrie   
Address:  Heiglhofstraße 65 81377 München Germany
Telephone: 00498971009236
Email: nikolai.jung@tum.de
Affiliation:  Technische Universität München
Name: Lehrstuhl für Sozialpädiatrie   
Address:  Heiglhofstraße 65 81377 München Germany
Telephone: 00498971009236
Email: nikolai.jung@tum.de
Affiliation:  Technische Universität München
Key inclusion & exclusion criteria
Inclusion criteria:
1. 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.
This includes:
- A woman who is not capable of bearing a child is defined as follows: post-menopausal (12 months natural (spontaneous) amenorrhea or 6 months spontaneous amenorrhea with serum-FSH-values (follicle-stimulating hormone) of >40 mIU/mL); 6 weeks after a bilateral ovariectomy with or without hysterectomy or sterilization by means of tubal ligation
- A woman capable of bearing child is defined as follows: a woman who is physiologically capable of becoming pregnant, including women whose occupation, lifestyle or sexual orientation exclude sexual intercourse with a male partner and women whose partners have been sterilized by vasectomy or other measures.
- Medically-approved methods of contraception can include the following: hormonal contraceptives, intrauterine device and double barrier method. Acceptable preventive measures can include total abstinence at the discretion of the investigator, in cases where compliance is ensured because of the study participant’s age, occupation, lifestyle or sexual orientation. Periodical abstinence (e.g. calendar, ovulation, symptothermal methods or abstinence until the 4th day after the ovulation) as well as coitus interruptus are not acceptable methods of contraception.
- A reliable method of contraception must be used for the entire duration of the study.
The dosage of oral contraceptives has to be doubled during the study period or two different methods of contraception should be combined.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. Epilepsy
2. Medication with known CNS effects
3. Severe mental retardation
4. Side effects during previous medication with and contraindications to 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Noonan Syndrom and Neurofibromatosis Type 1
MedDRA version: 20.0 Level: PT Classification code 10029748 Term: Noonan syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10029268 Term: Neurofibromatosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Not possible to specify
Intervention(s)

Product Name: Lovastatin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lovastatin
CAS Number: 75330-75-5
Other descriptive name: LOVASTATIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Lamotrigin beta
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Lamotrigin
CAS Number: 84057-84-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: Primary Objective:
Does the pharmacological intervention with (a) Lovastatin and (b) Lamotrigine improve synaptic plasticity in patients with Noonan syndrome and neurofibromatosis type 1.

Primary end point(s): Primary endpoint:
The primary efficacy endpoint analyses will be performed in three separate testing procedures:
I: Lovastatin vs. placebo on group 1
II: Lamotrigine vs. placebo on group 1
III: Lamotrigine vs. placebo on group 2
The global significance level will be 5%. Since experiments I and II are done on the same set of patients, the significance level for those two experiments will each be 2.5%. The significance level of experiment III will be 5%. The primary endpoint analysis will consist of three series of three paired samples two-sided t-tests, comparing MEP under Verum vs. placebo at the three measurement time points. The local significance level will be adjusted using the Bonferroni-Holm procedure.
All analyses will be performed on the full analysis set (FAS-I, FAS-II, FAS-III), consisting of all patients who delivered a full set of MEP measurements after interventional TMS within the corresponding experiment.
Secondary Objective: Secondary Objective:
Does the pharmacological intervention with (a) Lovastatin and (b) Lamotrigine improve attentional performance measured by the Test for Attentional Performance (TAP) in patients with Noonan syndrome and neurofibromatosis type 1.
Timepoint(s) of evaluation of this end point: Lovastatin and Lamotrigin have 2 timepoints
Secondary Outcome(s)
Secondary end point(s): Analyses of baseline data, secondary endpoints, and safety data will be done using appropriate descriptive statistics and paired samples tests for difference between the two study groups. All tests will be two-sided with an exploratory significance level of 5%. No adjustment for multiple comparisons will be done.
Another endpoint is the comparison of LTG and LOV effects on synaptic plasticity and attentional performance in the NS group.
Timepoint(s) of evaluation of this end point: Lovastatin and Lamotrigin have 2 timepoints
Secondary ID(s)
SYN-1748-MAL-0030-I
Source(s) of Monetary Support
BMBF DLR Projektträger Grant Number: 01 GM1519C
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 13/02/2018
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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