Cross-Species Multi-Modal Neuroimaging to Investigate GABA Physiology in Fragile X Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Non-displaceable binding potential of [18F]flumazenil (F18 FMZ)
研究概览
简要总结
The investigators wish to compare the brain distribution of GABA(A) receptors and GABA levels in young adult males with Fragile X Syndrome compared to idiopathic intellectual developmental disorder. The radiopharmaceutical [18F]flumazenil has been used to study GABA(A) receptor distribution in other genetic syndromes with autistic features; however, despite overwhelming evidence supporting the importance of the GABAergic system in FXS, no clinical investigation of this system in human FXS has been reported in the literature. Therefore, this study will provide the first in vivo comprehensive examination of the GABAergic system in FXS using hybrid positron emission tomography/ magnetic resonance imaging (PET/MRI).
详细描述
Fragile X syndrome (FXS) is the most common genetic cause of autism spectrum disorder (ASD). Converging evidence suggests that GABAergic dysfunction occurs in FXS. The investigators wish to examine brain distribution of GABA (A) receptors in young adult males with FXS using hybrid PET/MRI with [18F]flumazenil. This project will study the distribution of GABA(A) receptors in 15 young male adults with FXS (18-30 years old) compared to 15 age-matched male subjects with idiopathic intellectual developmental disorder (IDD) as controls. Simultaneous PET/MRI acquisition is an optimal technique to study in vivo GABAergic dysfunction and GABAa receptor distribution.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Fragile X Syndrome
Adult males aged 18-30 years diagnosed with FXS will undergo a non-invasive F18 FMZ PET/MRI scan to determine GABA(A) receptor density; developmental dynamics of GABA(A) receptor distribution, and structural neuroanatomy and connectional anatomy.
干预措施: [18F]flumazenil (Drug)
Idiopathic Intellectual Developmental Disorder
Adult males aged 18-30 years diagnosed with idiopathic intellectual developmental disorder will undergo a non-invasive F18 FMZ PET/MRI scan to determine GABA(A) receptor density; developmental dynamics of GABA(A) receptor distribution, and structural neuroanatomy and connectional anatomy.
干预措施: [18F]flumazenil (Drug)
结局指标
主要结局
Non-displaceable binding potential of [18F]flumazenil (F18 FMZ)
时间窗: Up to 2 hours per scan on a single study day
Binding potential provides an estimate of the GABA (A) receptor distribution and affinity of \[18F\]flumazenil-PET to the GABA receptors. Binding potential will be measured in patients with fragile X syndrome and control group comprising individuals with idiopathic intellectual developmental disorder. Using imaging data obtained from PET that was corrected for attenuation and partial volume effects by MRI, nuclear medicine physicians will draw regions of interest (ROI's) around the areas of the brain listed below to estimate the F18 FMZ non-displaceable binding potential (BPnd) of F18 FMZ to GABA (A) receptors in FXS.
GABA (A) receptor density in fragile X syndrome (FXS) patients relative to control group comprising individuals with idiopathic Intellectual Developmental Disorder (IDD)
时间窗: Up to 2 hours per scan on a single study day
Binding potential measurements will be compared between participants with fragile X syndrome and control group with idiopathic intellectual developmental disorder(IDD) using the PET radiotracer \[18F\]flumazenil-PET. Binding Potential (BPnd) is estimated as the distribution volume ratio (DVR) -1. DVR's of tracers are used in PET receptor studies where the radiopharmaceutical can be specifically bound to receptors; nonspecifically bound to other macromolecular components, or free in tissue (FT). DVR is calculated using a Logan Plot, which uses the dynamic PET images obtained during imaging and compartment modeling to graphically analyze by linear regression pharmacokinetic data for radiopharmaceuticals that undergo 'reversible' uptake. PET scans of FXS patients will be compared to the PET scans of control group.
次要结局
未报告次要终点
研究者
Frederick Chin, PhD
Assistant Professor (Research) of Radiology (General Radiology)
Stanford University