From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

NCT ID: NCT03826940

Last Updated: 2021-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-19

Study Completion Date

2020-08-31

Brief Summary

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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.

Detailed Description

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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

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Autism Spectrum Disorder Neurofibromatosis 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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NF1 - experimental

Group Type EXPERIMENTAL

Lovastatin 60 MG

Intervention Type DRUG

60 MG Lovastatin per day for 3 consecutive days

NF1 - control

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

60 MG Placebo per day for 3 consecutive days

ASD - experimental

Group Type EXPERIMENTAL

Lovastatin 60 MG

Intervention Type DRUG

60 MG Lovastatin per day for 3 consecutive days

ASD - control

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

60 MG Placebo per day for 3 consecutive days

Interventions

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Lovastatin 60 MG

60 MG Lovastatin per day for 3 consecutive days

Intervention Type DRUG

Placebos

60 MG Placebo per day for 3 consecutive days

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Coimbra

OTHER

Sponsor Role lead

Responsible Party

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Miguel Castelo-Branco

Research Director of CIBIT-ICNAS

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Miguel S Castelo-Branco, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

ICNAS - Institute of Nuclear Sciences Applied to Health

Locations

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ICNAS

Coimbra, , Portugal

Site Status

Countries

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Portugal

References

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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.

Reference Type BACKGROUND
PMID: 21766041 (View on PubMed)

Violante 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.

Reference Type BACKGROUND
PMID: 23404336 (View on PubMed)

Bernardino 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.

Reference Type DERIVED
PMID: 35970940 (View on PubMed)

Other Identifiers

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FLAD Life Science 2020

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CRU2C-ICNAS-001

Identifier Type: -

Identifier Source: org_study_id

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