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

April 1, 2021 updated by: Miguel Castelo-Branco, University of Coimbra

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
      • Coimbra, Portugal, 3000-043
        • ICNAS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: NF1 - experimental
Drug: Lovastatin 60 MG
60 MG Lovastatin per day for 3 consecutive days
PLACEBO_COMPARATOR: NF1 - control
Drug: Placebos
60 MG Placebo per day for 3 consecutive days
EXPERIMENTAL: ASD - experimental
Drug: Lovastatin 60 MG
60 MG Lovastatin per day for 3 consecutive days
PLACEBO_COMPARATOR: ASD - control
Drug: Placebos
60 MG Placebo per day for 3 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurochemical response changes to GABAergic stimulation
Time Frame: 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.
Through study completion, an average of 1 year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Coimbra

Investigators

  • Principal Investigator: Miguel S Castelo-Branco, MD, PhD, ICNAS - Institute of Nuclear Sciences Applied to Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 19, 2019

Primary Completion (ACTUAL)

March 31, 2020

Study Completion (ACTUAL)

August 31, 2020

Study Registration Dates

First Submitted

January 23, 2019

First Submitted That Met QC Criteria

January 31, 2019

First Posted (ACTUAL)

February 1, 2019

Study Record Updates

Last Update Posted (ACTUAL)

April 2, 2021

Last Update Submitted That Met QC Criteria

April 1, 2021

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRU2C-ICNAS-001
  • FLAD Life Science 2020 (Other Grant/Funding Number: Luso-American Development Foundation)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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