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| ID | Type | Description | Link |
|---|---|---|---|
| FLAD Life Science 2020 | Other Grant/Funding Number | Luso-American Development Foundation |
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This study aims to investigate synaptic physiology and behavioral inhibition in patients with NF1 and ASD and to answer whether inhibitory deficits at these levels are modulated by lovastatin.
Structure: (1) Visit 1: Baseline assessment- participant's characterization, baseline outcome measures and additional evaluations, (2) 3 consecutive days of physiologically probing drug/placebo intake, (3) Visit 2: Outcome measures and additional evaluations in the day after the last drug/placebo intake, (4) Washout period of 4 to 6 weeks, (5) 3 consecutive days of drug/placebo intake, (6) Visit 3: Outcome measures and additional evaluations in the day after the last placebo/drug intake.
The literature has shown synaptic inhibitory dysfunction in both ASD and NF1. Here the investigators aim to test whether a mechanistic link can be established between that synaptic inhibitory dysfunction, systems levels changes in oscillatory synchrony and regulation of inhibition and treatment with Lovastatin in these two neurodevelopmental disorders. The investigators will explore this link through the application of complementary quantitative measures (putative biomarkers), such as magnetic resonance spectroscopy (MRS) transcranial magnetic stimulation (TMS) and electroencephalogram (EEG) applied to the same group of adult patients before and after the lovastatin or placebo intake during three days.
The intervention comprehends three sessions: the first two visits will occur in the same week and the third visit will take place 4 to 6 weeks later. In the first visit (baseline assessment), participants will perform neuropsychological, EEG, MRS and TMS assessment. In the other two visits participants will repeat EEG, MRS and TMS assessments to study possible post- intervention effects. Participants will intake 60mg of Lovastatin or Placebo during three consecutive days before the second and the third visits.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NF1 - experimental | Experimental |
| |
| NF1 - control | Placebo Comparator |
| |
| ASD - experimental | Experimental |
| |
| ASD - control | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lovastatin 60 MG | Drug | 60 MG Lovastatin per day for 3 consecutive days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Neurochemical response changes to GABAergic stimulation | Comparing changes in brain excitation-inhibition measures (i.e., glutamate and GABA) when the GABAergic system is activated by oral dose of the Lovastatin 60mg during 3 days versus the placebo condition. | Through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Motor evoked potentials changes under motor cortical stimulation | Amplitudes (mV) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation | Through study completion, an average of 1 year |
| Cortical excitability changes under motor cortical stimulation |
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Inclusion Criteria:
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
Clinical diagnosis based on the well-established clinical criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Miguel S Castelo-Branco, MD, PhD | ICNAS - Institute of Nuclear Sciences Applied to Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ICNAS | Coimbra | 3000-043 | Portugal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21766041 | Background | Pizzarelli R, Cherubini E. Alterations of GABAergic signaling in autism spectrum disorders. Neural Plast. 2011;2011:297153. doi: 10.1155/2011/297153. Epub 2011 Jun 23. | |
| 23404336 | Background | Violante IR, Ribeiro MJ, Edden RA, Guimaraes P, Bernardino I, Rebola J, Cunha G, Silva E, Castelo-Branco M. GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact. Brain. 2013 Mar;136(Pt 3):918-25. doi: 10.1093/brain/aws368. Epub 2013 Feb 11. |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| D009456 | Neurofibromatosis 1 |
| D007266 | Inhibition, Psychological |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D017253 | Neurofibromatoses |
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| ID | Term |
|---|---|
| D008148 | Lovastatin |
| ID | Term |
|---|---|
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebos | Drug | 60 MG Placebo per day for 3 consecutive days |
|
Periods (ms) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation |
| Through study completion, an average of 1 year |
| Brain oscillations changes under sensory stimulation | Power (microV^2) will be recorded during sensory stimulation using high density electroencephalography. | Through study completion, an average of 1 year |
| Event-related potentials changes under sensory stimulation | Amplitude (microV) will be recorded during sensory stimulation using high density electroencephalography. | Through study completion, an average of 1 year |
| 35970940 | Derived | Bernardino I, Dionisio A, Castelo-Branco M. Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial. Sci Rep. 2022 Aug 15;12(1):13814. doi: 10.1038/s41598-022-17873-x. |
| D009455 | Neurofibroma |
| D018317 | Nerve Sheath Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009386 | Neoplastic Syndromes, Hereditary |
| D020752 | Neurocutaneous Syndromes |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001519 | Behavior |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |