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Completed

NCT Number: NCT03826940

From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

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.

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Key information

Conditions

Autism Spectrum Disorder Behavior Child Development Disorders, Pervasive Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Inhibition, Psychological Mental Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Nerve Tissue Neoplastic Syndromes, Hereditary Nerve Sheath Neoplasms Nervous System Diseases Neurocutaneous Syndromes Neurodegenerative Diseases Neurodevelopmental Disorders Neurofibroma Neurofibromatoses Neurofibromatosis 1 Neuromuscular Diseases Peripheral Nervous System Diseases

Age range

16 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

ICNAS

Coimbra, 3000-043, Portugal

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Lovastatin 60 MG

Drug

60 MG Lovastatin per day for 3 consecutive days

Placebos

Drug

60 MG Placebo per day for 3 consecutive days

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

University of Coimbra

Other

Registry information

Official study title

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

Acronym: ASD/NF1inhib

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Feb 1, 2019
Registry last updated
Apr 2, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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