From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

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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