Linking Inhibition From Molecular to Systems and Cognitive Levels: a Preclinical and Clinical Approach in Autism Spectrum Disorders and Neurofibromatosis.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Neurochemical response changes to GABAergic stimulation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
ASD - control
干预措施: Placebos (Drug)
NF1 - experimental
干预措施: Lovastatin 60 MG (Drug)
NF1 - control
干预措施: Placebos (Drug)
ASD - experimental
干预措施: Lovastatin 60 MG (Drug)
结局指标
主要结局
Neurochemical response changes to GABAergic stimulation
时间窗: 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.
次要结局
- Cortical excitability changes under motor cortical stimulation(Through study completion, an average of 1 year)
- Motor evoked potentials 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)
研究者
Miguel Castelo-Branco
Research Director of CIBIT-ICNAS
University of Coimbra