Brief Title
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1
Official Title
Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis.
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 Type
Interventional
Primary Outcome
Neurochemical response changes to GABAergic stimulation
Secondary Outcome
Motor evoked potentials changes under motor cortical stimulation
Condition
Autism Spectrum Disorder
Intervention
Lovastatin 60 MG
Study Arms / Comparison Groups
NF1 - experimental
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
16
Start Date
February 19, 2019
Completion Date
August 31, 2020
Primary Completion Date
March 31, 2020
Eligibility Criteria
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
Gender
All
Ages
16 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Miguel S Castelo-Branco, MD, PhD, ,
Location Countries
Portugal
Location Countries
Portugal
Administrative Informations
NCT ID
NCT03826940
Organization ID
CRU2C-ICNAS-001
Secondary IDs
FLAD Life Science 2020
Responsible Party
Principal Investigator
Study Sponsor
University of Coimbra
Study Sponsor
Miguel S Castelo-Branco, MD, PhD, Principal Investigator, ICNAS - Institute of Nuclear Sciences Applied to Health
Verification Date
November 2020