From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1 (ASD/NF1inhib)
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| ClinicalTrials.gov Identifier: NCT03826940 |
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Recruitment Status :
Completed
First Posted : February 1, 2019
Last Update Posted : April 2, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autism Spectrum Disorder Neurofibromatosis 1 | Drug: Lovastatin 60 MG Drug: Placebos | Not Applicable |
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 (Clinical Trial) |
| Actual Enrollment : | 16 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Basic Science |
| Official Title: | Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis. |
| Actual Study Start Date : | February 19, 2019 |
| Actual Primary Completion Date : | March 31, 2020 |
| Actual Study Completion Date : | August 31, 2020 |
| 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 |
- 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.
- 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
- 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
- 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.
- 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.
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| Ages Eligible for Study: | 16 Years to 65 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03826940
| Portugal | |
| ICNAS | |
| Coimbra, Portugal, 3000-043 | |
| Principal Investigator: | Miguel S Castelo-Branco, MD, PhD | ICNAS - Institute of Nuclear Sciences Applied to Health |
| Responsible Party: | Miguel Castelo-Branco, Research Director of CIBIT-ICNAS, University of Coimbra |
| ClinicalTrials.gov Identifier: | NCT03826940 |
| Other Study ID Numbers: |
CRU2C-ICNAS-001 FLAD Life Science 2020 ( Other Grant/Funding Number: Luso-American Development Foundation ) |
| First Posted: | February 1, 2019 Key Record Dates |
| Last Update Posted: | April 2, 2021 |
| Last Verified: | November 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| 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 |
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Inhibition GABA molecular imaging |
functional magnetic resonance imaging Autism Spectrum Disorder Neurofibromatosis 1 |
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Neurofibromatoses Neurofibromatosis 1 Neurofibroma Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders Nerve Sheath Neoplasms Neoplasms, Nerve Tissue Neoplasms by Histologic Type Neoplasms Neoplastic Syndromes, Hereditary Neurocutaneous Syndromes Nervous System Diseases |
Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Peripheral Nervous System Diseases Neuromuscular Diseases Peripheral Nervous System Neoplasms Nervous System Neoplasms Lovastatin L 647318 Dihydromevinolin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents |