From Molecules to Cognition: Inhibitory Mechanisms in ASD and NF1

NCT03826940 | Completed

• 2 other identifiers: CRU2C-ICNAS-001FLAD Life Science 2020
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Autism Spectrum Disorder; Neurofibromatosis 1

Keywords

Inhibition; GABA; molecular imaging; functional magnetic resonance imaging; Autism Spectrum Disorder; Neurofibromatosis 1

Outcome Measures

Primary Outcomes (1)

• 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.

  Through study completion, an average of 1 year

Secondary Outcomes (4)

• Motor evoked potentials changes under motor cortical stimulation

  Through study completion, an average of 1 year

• Cortical excitability changes under motor cortical stimulation

  Through study completion, an average of 1 year

• Brain oscillations changes under sensory stimulation

  Through study completion, an average of 1 year

• Event-related potentials changes under sensory stimulation

  Through study completion, an average of 1 year

Study Arms (4)

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

Interventions

Lovastatin 60 MG DRUG

60 MG Lovastatin per day for 3 consecutive days

ASD - experimental; NF1 - experimental

Placebos DRUG

60 MG Placebo per day for 3 consecutive days

ASD - control; NF1 - control

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Coimbra: lead

Study Sites (1)

ICNAS

Coimbra, 3000-043, Portugal

Location

Related Publications (3)

• 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.

  PMID: 21766041 BACKGROUND

• 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.

  PMID: 23404336 BACKGROUND

• 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.

  PMID: 35970940 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder; Neurofibromatosis 1; Inhibition, Psychological

Interventions

Lovastatin

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurofibromatoses; Neurofibroma; 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; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Miguel S Castelo-Branco, MD, PhD

  ICNAS - Institute of Nuclear Sciences Applied to Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Director of CIBIT-ICNAS

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: February 1, 2019
• Study Start: February 19, 2019
• Primary Completion: March 31, 2020
• Study Completion: August 31, 2020
• Last Updated: April 2, 2021

Record last verified: 2020-11

Locations

PT (1)