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lack of enrollment
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alprazolam (A) | Active Comparator | Alprazolam (Xanax), gel-capsule, 1mg, single-dose, 1-day |
|
| Dextroamphetamine (D) | Active Comparator | Dextroamphetamine (Dexedrine), gel-capsule, 20mg, single-dose, 1-day |
|
| Placebo (P) | Placebo Comparator | Placebo gel-capsule, single-dose, 1-day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alprazolam | Drug | Alprazolam, gel-capsule, 1mg, single-dose, 1-day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | 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 | 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 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John E Jensen, Ph.D. | Mclean Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McLean Imaging Center, McLean Hospital | Belmont | Massachusetts | 02478-9106 | United States |
At present, there is no plan to share IPD data.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dextroamphetamine, Alprazolam, Placebo Sequence | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day Placebo: single-dose, 1-day |
| FG001 | Alprazolam, Dextroamphetamine, Placebo Sequence | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day Placebo: single-dose, 1-day |
| FG002 | Placebo, Dextroamphetamine, Alprazolam Sequence | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day Placebo: single-dose, 1-day |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (1 Day) |
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| Washout (at Least 1 Week) |
| |||||||||||||
| Second Intervention (1 Day) |
| |||||||||||||
| Washout (at Least 1 Week) |
| |||||||||||||
| Third Intervention (1 Day) |
|
Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
Adverse events were monitored throughout the entire clinical study which (including a no-cost extension) was of 1 year, 6 month duration, until the study closed to recruitment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Alprazolam | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. J. Eric Jensen | McLean Hospital | 617-855-3366 | ejensen@mclean.harvard.edu |
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| ID | Term |
|---|---|
| D000525 | Alprazolam |
| D003913 | Dextroamphetamine |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Dextroamphetamine | Drug | Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day |
|
|
| Placebo | Other | Placebo, gel-capsule, single-dose, 1-day |
|
| 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 | 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 | 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 | 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) |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Alprazolam: Alprazolam, gel-capsule, 1mg, single-dose, 1-day |
| OG002 | Dextroamphetamine | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day |
|
|
| Primary | Left Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| Primary | Left Temporal: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | One participant is missing GABA level at t4 while on Placebo, and one participant is missing GABA level at t2 while on Alprazolam. | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| Primary | Parieto-Occipital: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| Primary | Right Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | One participant ismissing GABA level at t4 while on Dextroamphetamine | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| Primary | Right Basal-Ganglia: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | One participant is missing GABA level at t4 while on Dextroamphetamine. | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| Primary | Right Temporal: Percent Change in GABA Levels After an Acute Drug Challenge | 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 | One participant is missing GABA level at t4 while on Dextroamphetamine. Another participant is missing GABA levels both at t2 and t4 while on Dextroamphetamine. Another participant is missing GABA levels at both t2 and t4 while on Alprazolam. | Posted | Median | Inter-Quartile Range | percent change | 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) |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| EG001 | Dextroamphetamine | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Dextroamphetamine: Dextroamphetamine, gel-capsule, 20mg, single-dose, 1-day | 0 | 7 | 0 | 7 |
| EG002 | Placebo | Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning Placebo, single-dose, 1-day | 0 | 7 | 0 | 7 |
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| D006571 | Heterocyclic Compounds |
| D000661 | Amphetamine |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
|
| t1 to t4: 45min-102min |
|
| t2 to t3: 64min-83min |
|
| t3 to t4: 83min-102min |
|
| t2 to t4: 64min-102min |
|
| t1 to t3: 45min-83min |
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| t1 to t4: 45min-102min |
|
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| t2 to t3: 64min-83min |
|
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| t3 to t4: 83min-102min |
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| t2 to t4: 64min-102min |
|
|
| t1 to t3: 45min-83min |
|
| t1 to t4: 45min-102min |
|
| t2 to t3: 64min-83min |
|
| t3 to t4: 83min-102min |
|
| t2 to t4: 64min-102min |
|
| t1 to t3: 45min-83min |
|
|
| t1 to t4: 45min-102min |
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|
| t2 to t3: 64min-83min |
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| t3 to t4: 83min-102min |
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| t2 to t4: 64min-102min |
|
|
| t1 to t3: 45min-83min |
|
|
| t1 to t4: 45min-102min |
|
|
| t2 to t3: 64min-83min |
|
|
| t3 to t4: 83min-102min |
|
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| t2 to t4: 64min-102min |
|
|
| t1 to t3: 45min-83min |
|
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| t1 to t4: 45min-102min |
|
|
| t2 to t3: 64min-83min |
|
|
| t3 to t4: 83min-102min |
|
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| t2 to t4: 64min-102min |
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