Autism Spectrum DisorderASD/NF1inhibNCT03826940
From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1
A study testing Lovastatin 60 MG in people with Autism Spectrum Disorder and Neurofibromatosis 1, run by University of Coimbra at 1 site in Portugal.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Autism Spectrum Disorder, Neurofibromatosis 1
- What is being tested?
- Lovastatin 60 MG
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 sitePortugal
- Study dates
- 19 Feb 2019to 31 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Autism Spectrum Disorder, Neurofibromatosis 1
- Being tested
- Lovastatin 60 MG, Placebos
- Keywords
- Inhibition, GABA, molecular imaging, functional magnetic resonance imaging, Autism Spectrum Disorder, Neurofibromatosis 1
- Medical subject headings
- Autism Spectrum Disorder, Neurofibromatosis 1, Inhibition, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lovastatin 60 MGDrug
60 MG Lovastatin per day for 3 consecutive days
PlacebosDrug
60 MG Placebo per day for 3 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| NF1 - experimental | Experimental | Not described Receives: Drug: Lovastatin 60 MG |
| NF1 - control | Placebo comparator | Not described Receives: Drug: Placebos |
| ASD - experimental | Experimental | Not described Receives: Drug: Lovastatin 60 MG |
| ASD - control | Placebo comparator | Not described Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurochemical response changes to GABAergic stimulation
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.
Measured: Through study completion, an average of 1 year
Secondary outcomes (4)
Motor evoked potentials changes under motor cortical stimulation
Amplitudes (mV) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation
Measured: Through study completion, an average of 1 year
Cortical excitability changes under motor cortical stimulation
Periods (ms) will be measured during stimulation of the primary motor cortex using transcranial magnetic stimulation
Measured: Through study completion, an average of 1 year
Brain oscillations changes under sensory stimulation
Power (microV^2) will be recorded during sensory stimulation using high density electroencephalography.
Measured: Through study completion, an average of 1 year
Event-related potentials changes under sensory stimulation
Amplitude (microV) will be recorded during sensory stimulation using high density electroencephalography.
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start19 Feb 2019
- Primary completion31 Mar 2020
- Study completion31 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autism Spectrum DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Coimbra
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miguel Castelo-Branco, University of Coimbra
- Investigators
- Miguel S Castelo-Branco, MD, PhD, Principal investigator, ICNAS - Institute of Nuclear Sciences Applied to Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03826940
- Sponsor's protocol ID
- CRU2C-ICNAS-001
- Other IDs
- FLAD Life Science 2020
- Acronym
- ASD/NF1inhib
- Status last verified
- Nov 2020
- First submitted
- 23 Jan 2019
- Last updated
- 2 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Pizzarelli R, Cherubini E. Alterations of GABAergic signaling in autism spectrum disorders. Neural Plast. 2011;2011:297153. doi: 10.1155/2011/297153. Epub 2011 Jun 23.
PubMed 21766041Violante IR, Ribeiro MJ, Edden RA, Guimaraes P, Bernardino I, Rebola J, Cunha G, Silva E, Castelo-Branco M. GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact. Brain. 2013 Mar;136(Pt 3):918-25. doi: 10.1093/brain/aws368. Epub 2013 Feb 11.
PubMed 23404336Bernardino I, Dionisio A, Castelo-Branco M. Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial. Sci Rep. 2022 Aug 15;12(1):13814. doi: 10.1038/s41598-022-17873-x.
PubMed 35970940
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis.
- ClinicalTrials.gov ID
- NCT03826940
- Acronym / sponsor ID
- ASD/NF1inhib / CRU2C-ICNAS-001
- Conditions
- Autism Spectrum Disorder, Neurofibromatosis 1
- Keywords
- Inhibition, GABA, molecular imaging, functional magnetic resonance imaging, Autism Spectrum Disorder, Neurofibromatosis 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of CoimbraUniversity, hospital or other
- Study start
- 19 Feb 2019 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Aug 2020 (actual)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NF1 - experimental | Experimental | Drug: Lovastatin 60 MG |
| NF1 - control | Placebo comparator | Drug: Placebos |
| ASD - experimental | Experimental | Drug: Lovastatin 60 MG |
| ASD - control | Placebo comparator | Drug: Placebos |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lovastatin 60 MG60 MG Lovastatin per day for 3 consecutive days | Drug | ASD - experimental, NF1 - experimental |
| Placebos60 MG Placebo per day for 3 consecutive days | Drug | ASD - control, NF1 - control |
Primary outcome
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.
4 secondary outcomes
Motor evoked potentials changes under motor cortical stimulation
Time frame: 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
Brain oscillations changes under sensory stimulation
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
- Background: PubMed 21766041Pizzarelli R, Cherubini E. Alterations of GABAergic signaling in autism spectrum disorders. Neural Plast. 2011;2011:297153. doi: 10.1155/2011/297153. Epub 2011 Jun 23.
- Background: PubMed 23404336Violante IR, Ribeiro MJ, Edden RA, Guimaraes P, Bernardino I, Rebola J, Cunha G, Silva E, Castelo-Branco M. GABA deficit in the visual cortex of patients with neurofibromatosis type 1: genotype-phenotype correlations and functional impact. Brain. 2013 Mar;136(Pt 3):918-25. doi: 10.1093/brain/aws368. Epub 2013 Feb 11.
- Derived from this study: PubMed 35970940Bernardino I, Dionisio A, Castelo-Branco M. Cortical inhibition in neurofibromatosis type 1 is modulated by lovastatin, as demonstrated by a randomized, triple-blind, placebo-controlled clinical trial. Sci Rep. 2022 Aug 15;12(1):13814. doi: 10.1038/s41598-022-17873-x.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miguel S Castelo-Branco, MD, PhD principal investigator
ICNAS - Institute of Nuclear Sciences Applied to Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lovastatin 60 MG in people with Autism Spectrum Disorder and Neurofibromatosis 1, run by University of Coimbra at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurochemical response changes to GABAergic stimulation (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03826940, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2021.