- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01577706
Spectroscopic Imaging at 4T: A Drug Challenge Study (CEBRA2)
Spectroscopic Imaging of GABA and Glutamate/Glutamine in Healthy Volunteers at 4T: A Double Blind, Crossover Drug Challenge Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Massachusetts
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Belmont, Massachusetts, United States, 02478-9106
- McLean Imaging Center, McLean Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Alprazolam (A)
Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day
|
Alprazolam, gel-capsule, 1mg, single-dose, 1-day
Other Names:
|
Active Comparator: Dextroamphetamine (D)
Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day
|
Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day
Other Names:
|
Placebo Comparator: Placebo (P)
Placebo gel-capsule, single-dose, 1-day
|
Placebo, gel-capsule, single-dose, 1-day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Left Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Left Temporal: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Right Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Right Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Right Temporal: Percent Change in GABA Levels After an Acute Drug Challenge
Time Frame: from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
The primary goal of this study is to assess the efficacy of an advanced spectroscopic imaging protocol in detecting changes in the levels of brain GABA in response to an acute drug challenge. GABA levels are expressed as a ratio to total creatinine: GABA/Cr percent change = 100*(later timepoint - earlier timepoint) / earlier timepoint |
from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals (4 time points at t1: 45, t2: 64, t3: 83, t4: 102 minutes post-dose)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John E Jensen, Ph.D., McLean Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Hypnotics and Sedatives
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Dopamine Uptake Inhibitors
- Central Nervous System Stimulants
- Dextroamphetamine
- Alprazolam
Other Study ID Numbers
- 2012P000197
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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