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Lovastatin

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60 MG Lovastatin per day for 3 consecutive days

Lovastatin 60 MG

60 MG Placebo per day for 3 consecutive days

Placebos

Miguel S Castelo-Branco, MD, PhD

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.

From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis.

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.

Amplitudes (mV) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation

Periods (ms) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation

Power (microV\^2) will be recorded during sensory stimulation using high density electroencephalography.

Amplitude (microV) will be recorded during sensory stimulation using high density electroencephalography.

University of Coimbra

Research Director of CIBIT-ICNAS

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1	NCT03826940	Autism Spectrum... Neurofibromatos...	Lovastatin 60 M... Placebos	16 Years - 65 Years	University of Coimbra

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