From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1 (ASD/NF1inhib)

University of Coimbra

Status: Completed

Conditions: Autism Spectrum Disorder; Neurofibromatosis 1

Treatments: Drug: Lovastatin 60 MG; Drug: Placebos

Study type: Interventional

Funder types: Other

Identifiers

NCT03826940

FLAD Life Science 2020 (Other Grant/Funding Number)

CRU2C-ICNAS-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 16 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Positive diagnostic results for ASD in:

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.

• Positive diagnostic results for NF1:

Clinical diagnosis based on the well-established clinical criteria

Exclusion criteria

• Global Intelligence Quotient < 80
• Associated medical condition such as epilepsy, neurologic conditions, genetic syndromes, or other usual comorbidity in ASD and NF1 populations
• Medication capable of interfering with the intervention and/or study results
• Pregnancy
• Drug use and/or alcohol abuse
• Contra-indications to MR and TMS

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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16 participants in 4 patient groups, including a placebo group

NF1 - experimental

Experimental group

Treatment:

Drug: Lovastatin 60 MG

NF1 - control

Placebo Comparator group

Treatment:

Drug: Placebos

ASD - experimental

Experimental group

Treatment:

Drug: Lovastatin 60 MG

ASD - control

Placebo Comparator group

Treatment:

Drug: Placebos