Spectroscopic Imaging of GABA and Glutamate/Glutamine in Healthy Volunteers at 4T: A Double Blind, Crossover Drug Challenge Study

Mclean Hospital1 个研究点分布在 1 个国家目标入组 7 人开始时间: 2013年6月最近更新: 2017年4月4日

适应症

干预措施

试验速览

阶段: 不适用
状态: 终止
发起方: Mclean Hospital
入组人数: 7
试验地点: 1
主要终点: Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

An advanced technique for rapid magnetic resonance proton spectroscopic imaging (1H-MRSI) will be employed in a drug challenge study in healthy volunteers to spatially map and measure acute changes in the brain chemicals GABA, glutamate and glutamine after administration of a drug. Three condition will be tested in a double-blind fashion, i)depressant, ii)stimulant, iii)placebo. It is hypothesized that unique and reproducible spatial and directional metabolic response patterns will be observed, unique to each condition within the brain.

详细描述

Proton magnetic resonance spectroscopy (1H MRS) is a powerful tool for assessing neurochemistry non-invasively in vivo. However, the primary shortcoming in most studies is the lack of spatial coverage afforded by the typical single-voxel design. Limits on participant tolerance and financial resources restrict single-voxel studies to an examination of one or two carefully chosen voxels per scan, thus inadequately addressing the question of focal vs. global pathophysiology. A secondary shortcoming is that most studies report on either GABA or glutamate-glutamine (Glu-Gln) due to the technically demanding spectral-editing techniques that must be implemented in order to resolve and quantify those metabolites with any accuracy.

1H MRS imaging (MRSI) can partially overcome these limitations by providing a global picture of brain chemistry rather than just the focal snapshot afforded by the single-voxel design. However, the scan time necessary for collecting enough data for adequate spatial resolution and signal-to-noise, particularly if also using specialized spectral-editing techniques, is still too lengthy. We recently developed a method that combines Spectroscopic Imaging with the MEGAPRESS-based difference-editing acquisition for optimal GABA detection as well as for optimal detection of Glu and Gln. This MEGACSI sequence will permit us to obtain the maximum amount of neurochemical information in a clinically sound scan time, while using the current state-of-the-art MRS editing methods for optimal detection of GABA, Glu, and Gln.

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: Double (Participant, Investigator)

入排标准

年龄范围: 21 Years 至 45 Years（Adult）
性别: Male
接受健康志愿者: 是

入选标准

•Participants will be male volunteers between the ages of 21-45
•Non-smoking participants are preferred, but will admit those who smoke less than 5 cigarettes per day
•Participants must be able to read screening materials including consent form and give informed consent

排除标准

•Participants cannot meet DSM-IV criteria for lifetime and/or current mood, anxiety, psychotic, and alcohol/drug use disorders as identified by the SCID
•Participants cannot be taking any prescription medication (except oral contraceptives, certain short-term anti-fungal agents, and some topical creams for dermal conditions) or nutritional supplements
•Participants cannot be taking any psychotropic medications
•Participants cannot have a history of major head trauma resulting in cognitive impairment, seizure, or other neurological disorders.
•Participants cannot have any conditions that are contraindicated for MRI
•Participants cannot have a family history of alcoholism
•Participants cannot have any abnormal blood chemistries/urinalysis results or any other medical condition that may affect drug disposition (e.g., Hepatitis C)
•Participants cannot have current or past cardiac problems, and they also cannot have a family history of sudden death or ventricular arrhythmia
•Participants who, in the investigators' judgment, will not likely be able to comply with the study protocol.
•Participants cannot have any clinically significant findings in the structural anatomic brain scans (per the MRI report read by a board-certified radiologist).

研究组 & 干预措施

Alprazolam (A)

Active Comparator

Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day

干预措施: Alprazolam (Drug)

Dextroamphetamine (D)

Active Comparator

Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day

干预措施: Dextroamphetamine (Drug)

Placebo (P)

Placebo Comparator

Placebo gel-capsule, single-dose, 1-day

干预措施: Placebo (Other)