From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

Not Applicable

Completed

• Conditions: Autism Spectrum Disorder; Neurofibromatosis 1
• Interventions: Drug: Placebos; Drug: Lovastatin 60 MG

• Registration Number: NCT03826940
• Lead Sponsor: University of Coimbra

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-01-23
• Study First Submitted QC: 2019-01-31
• Study First Posted: 2019-02-01
• Study Start: 2019-02-19
• Primary Completion: 2020-03-31
• Study Completion: 2020-08-31
• Status Verified: 2020-11
• Last Update Submitted: 2021-04-01
• Last Update Posted: 2021-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
NF1 - control	Placebos	-
ASD - experimental	Lovastatin 60 MG	-
NF1 - experimental	Lovastatin 60 MG	-
ASD - control	Placebos	-

Primary Outcome Measures

Name	Time	Method
Neurochemical response changes to GABAergic stimulation	Through study completion, an average of 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Cortical excitability changes under motor cortical stimulation	Through study completion, an average of 1 year	Periods (ms) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation
Motor evoked potentials changes under motor cortical stimulation	Through study completion, an average of 1 year	Amplitudes (mV) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation
Brain oscillations changes under sensory stimulation	Through study completion, an average of 1 year	Power (microV\^2) will be recorded during sensory stimulation using high density electroencephalography.
Event-related potentials changes under sensory stimulation	Through study completion, an average of 1 year	Amplitude (microV) will be recorded during sensory stimulation using high density electroencephalography.

Trial Locations

Locations (1)

ICNAS; 🇵🇹 Coimbra, Portugal