This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Spectroscopic Imaging at 4T: A Drug Challenge Study (NCT01577706), a randomized na study. The primary outcome is Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01577706 |
| Phase | NA |
| Condition | AOD Effects and Consequences |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Mclean Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers enrolled in a study of spectroscopic imaging. The registry record lists enrollment as 7; further eligibility details are not reported in the registry record.
Intervention
Acute drug challenges with alprazolam, described as a single-dose 1mg gel-capsule, or dextroamphetamine, described as a single-dose 20mg gel-capsule.
Comparator
A single-dose placebo gel-capsule. The study description identifies three conditions: depressant, stimulant, and placebo.
Primary question
Can 4T magnetic resonance proton spectroscopic imaging detect changes in brain GABA after an acute drug challenge, with the primary measure focused on percent change in left-thalamus GABA levels relative to creatinine?
The research question is principally about measurement: whether an advanced imaging protocol can detect brain-chemical changes after the challenge conditions. The registry describes a hypothesis that each condition would be associated with a distinctive spatial and directional metabolic response pattern. That is a stated hypothesis, not a result. The primary endpoint is narrower, specifying percent change in left-thalamus GABA levels relative to total creatinine over post-dose measurement times.
The listed conditions allow the investigators to examine measurements under alprazolam, dextroamphetamine, and placebo. The record does not report the order in which participants received these conditions, the washout arrangements, or the observed GABA values. It therefore cannot establish from the registered information whether the imaging protocol detected a condition-specific pattern or how the conditions compared.
3. Trial Design
The registry identifies this as a randomized, double-blind crossover study. Its official title describes healthy volunteers studied with spectroscopic imaging of GABA and glutamate/glutamine at 4T. The brief summary describes three challenge conditions: depressant, stimulant, and placebo. The listed interventions are alprazolam, dextroamphetamine, and placebo. The study status is terminated.
In a crossover design, the same participant may receive more than one study condition, so measurements can be compared within participants as well as across conditions. This general feature can help account for stable differences between participants. The registry does not report the sequence of conditions, how randomization was implemented, whether a washout period was used, or how period and sequence effects were handled. These details matter when interpreting repeated measurements after drug challenges.
Double masking means the record characterizes the study as blinded for two parties, but the identities of those parties and the procedures used to preserve masking are not reported in the registry record. The entry gives enrollment as 7. That figure should not be interpreted as the number of independent observations for every condition: the design is crossover, and the registry lists seven participants at risk in each intervention group for the adverse-event reporting. The record does not describe exclusions, completion, or the number of participants contributing data to the primary endpoint.
The registry gives a start of 2013-06 and primary completion of 2013-12. The phase is listed as NA. It does not report a detailed protocol, randomization schedule, or account of why the study was terminated. Those missing details limit assessment of implementation and the completeness of the planned comparisons.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
First Intervention (1 Day)
| Stage | Dextroamphetamine, Alprazolam, Placebo Sequence | Alprazolam, Dextroamphetamine, Placebo Sequence | Placebo, Dextroamphetamine, Alprazolam Sequence |
|---|---|---|---|
| STARTED | 3 | 1 | 3 |
| COMPLETED | 3 | 1 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
Washout (at Least 1 Week)
| Stage | Dextroamphetamine, Alprazolam, Placebo Sequence | Alprazolam, Dextroamphetamine, Placebo Sequence | Placebo, Dextroamphetamine, Alprazolam Sequence |
|---|---|---|---|
| STARTED | 3 | 1 | 3 |
| COMPLETED | 3 | 1 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
Second Intervention (1 Day)
| Stage | Dextroamphetamine, Alprazolam, Placebo Sequence | Alprazolam, Dextroamphetamine, Placebo Sequence | Placebo, Dextroamphetamine, Alprazolam Sequence |
|---|---|---|---|
| STARTED | 3 | 1 | 3 |
| COMPLETED | 3 | 1 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
Washout (at Least 1 Week)
| Stage | Dextroamphetamine, Alprazolam, Placebo Sequence | Alprazolam, Dextroamphetamine, Placebo Sequence | Placebo, Dextroamphetamine, Alprazolam Sequence |
|---|---|---|---|
| STARTED | 3 | 1 | 3 |
| COMPLETED | 3 | 1 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Healthy male volunteers receiving drug and undergoing 1H-MRSI scanning
| Characteristic | Unit | All Study Participants |
|---|---|---|
| Participants analysed | 7 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 28.9 (SD 7.6) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 7 |
| Region of Enrollment: United States | participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge, measured over 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).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percent change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled “Left Thalamus: Percent Change in GABA Levels After an Acute Drug Challenge.” It measures the change in GABA relative to total creatinine, rather than an absolute concentration. The record defines the percent-change calculation as 100 multiplied by the difference between a later and earlier timepoint, divided by the earlier timepoint. This expresses the change relative to the earlier measurement.
The endpoint covers measurements from 45 minutes post-dose to 102 minutes post-dose in 19-minute intervals, with measurements at t1: 45, t2: 64, t3: 83, and t4: 102 minutes post-dose. The registered summary statistic is the median, with inter-quartile range as the measure of dispersion. The median describes the middle of a set of observations, while the inter-quartile range describes the spread of the central portion of those observations. These summaries can be useful when measurements are skewed or influenced by extreme values.
The endpoint was selected to assess whether the imaging protocol could detect acute changes in brain GABA. A ratio to creatinine can provide a reference for interpreting signal changes, but it does not remove every source of measurement uncertainty. The registry record does not report the endpoint values, the inter-quartile ranges, or a condition-specific comparison. It also does not specify which pair or sequence of timepoints constituted the primary statistical contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a study intended to assess an imaging method, not a clinical treatment outcome. Its central question is whether 4T spectroscopic imaging can detect acute changes in brain GABA after drug challenge. The stated hypothesis concerns distinctive spatial and directional metabolic response patterns across the conditions. The record does not report results establishing whether those patterns were observed.
Although the primary endpoint is defined in detail, its numerical results are not reported in the registry record. There is no posted median percent change or inter-quartile range for the left thalamus, and no reported estimate of a difference between alprazolam, dextroamphetamine, and placebo. Without such estimates, the magnitude and direction of any change cannot be assessed. Precision also cannot be judged: no confidence interval or other uncertainty measure for a condition contrast is reported.
The endpoint involves repeated post-dose measurements, but the registry does not identify a single comparison that represents the primary result. The record notes that the primary outcome has several time points and was not reduced to one comparison. A trajectory across measurement times could be informative, but it is not interchangeable with a single change estimate. The time-specific values and the method for comparing them are not reported in the registry record.
Enrollment is listed as 7, and the study is marked terminated. Those details describe the registered study, but they do not indicate how many participants completed all conditions or contributed analyzable endpoint data. The record does not report reasons for termination, missing measurements, or analysis populations. As a result, the extent to which the registered enrollment corresponds to the results available for analysis is unclear.
The absence of reported endpoint results is not evidence that the imaging protocol failed, nor does it support a conclusion that any challenge changed GABA. It means the registry record does not provide the outcome information required to evaluate those questions. The stated hypothesis and endpoint definition describe what the study sought to assess; they should not be read as findings. The adverse-event entries are also limited to recorded event counts and should not be treated as a full account of safety or tolerability.
9. Statistical Methods Explained
The study combines a crossover drug challenge with repeated imaging measurements. Interpreting such a design requires attention to both the within-participant structure and the time course of the endpoint. The registry identifies randomization, double masking, and crossover allocation, but it does not report the detailed statistical analysis plan. The distinctions below explain general statistical concepts; they do not establish which methods the investigators used.
What does crossover allocation change?
In a crossover study, participants can receive multiple conditions, with measurements collected under each. A within-participant comparison can reduce the influence of stable characteristics that differ between people. However, observations from the same participant are related, not independent. Analyses generally need to account for this dependence. The order of conditions can also matter if responses carry over, if measurements change over time for reasons unrelated to treatment, or if the challenge in an earlier period affects a later period. The registry record does not report condition sequence, washout procedures, or an analysis of period, sequence, or carryover effects.
Randomization may help prevent systematic allocation patterns, but the label alone does not reveal how the sequence was generated or concealed. Those implementation details are not reported in the registry record. Double masking is also identified, but the masked parties and the assessment of masking are not reported. These omissions prevent a detailed review of how potential sources of bias were addressed.
Why report a median and inter-quartile range?
The registered endpoint uses the median and inter-quartile range. In general, the median is less affected by unusually high or low observations than the mean. The inter-quartile range describes dispersion among the central observations, rather than the precision of an estimated treatment contrast. These descriptive summaries can characterize a distribution, but they do not by themselves show whether conditions differ reliably. A confidence interval for a contrast would communicate uncertainty around that contrast; such an interval is not reported in the registry record.
The endpoint is a percent change in GABA/Cr, with later and earlier timepoints used in the stated calculation. Relative changes can be difficult to interpret without the underlying measurements and a clearly defined comparison. If an earlier value is noisy or unusually small, a relative change can be unstable. This is a general property of ratio-based change measures, not a claim about the measurements in this study. The record does not report underlying GABA/Cr values or explain how any measurement-quality concerns were handled.
Why do the repeated timepoints matter?
Measurements at t1: 45, t2: 64, t3: 83, and t4: 102 minutes post-dose create a time-course question, not merely a single endpoint contrast. An analysis might examine changes at each timepoint, an overall trajectory, or a prespecified contrast between selected times. Those approaches answer different questions. Repeated testing across timepoints can also increase the chance of a notable result arising by chance if multiplicity is not addressed. The registry record does not report a model for repeated measurements, a chosen summary contrast, or a multiplicity adjustment.
For repeated measures, methods commonly account for correlation between observations from the same participant. The correlation structure and modeling choices can affect standard errors and confidence intervals. If participants have incomplete measurements, the method for using available data may also affect results. Neither the correlation model nor the handling of incomplete observations is reported in the registry record.
What can be inferred from the analysis information?
The registry lists 7 outcome measures and records 0 analyses. Those entries do not provide a statistical model, an analysis population, or a treatment-effect estimate. A lack of analyses recorded in the registry is not a description of every analysis that may have been conducted; it means that analysis details and results are not reported in the registry record. The record also does not report a sample-size justification or a protocol-based power calculation.
The planning framework described in the registry uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. Such calculations, when available, are planning illustrations rather than observed power. In this study, the primary endpoint has multiple timepoints and has not been reduced to one comparison, so no single comparison-based planning estimate is reported. The record does not support an inference about the study’s power or the probability that it would detect a particular effect.
Finally, a statistical result would need to be interpreted alongside the measurement protocol and the study’s small enrollment. Statistical significance, if reported, would not by itself establish that a signal is reproducible or that it has clinical importance. For a technical imaging question, the estimated size, uncertainty, consistency across timepoints and conditions, and completeness of the data would all be relevant. The registry record does not report those results.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity is relevant because the primary endpoint includes repeated post-dose measurements, and the registry lists 7 outcome measures. Examining multiple outcomes, conditions, or timepoints can create multiple opportunities to find an apparently notable result by chance. In general, a prespecified analysis plan can identify which comparisons are primary and whether adjustment or a hierarchical testing strategy is appropriate. The registry record does not report such a plan or a multiplicity adjustment.
The primary outcome is not reduced to one comparison in the registry record. It does not specify whether the intended primary inference was a comparison at a selected time, a pattern across time, or another summary. Without that definition, the analysis target and the role of any secondary outcomes are unclear. The registry records 0 analyses, so no analysis-specific multiplicity procedure is reported.
Missing-data methods and analysis populations are not reported in the registry record. It does not state how many participants completed all challenge conditions, whether all scheduled imaging measurements were obtained, why any data might be missing, or how incomplete records were handled. In a crossover study, missing observations can affect within-participant comparisons and can leave different amounts of information for different conditions. The record does not describe imputation, exclusion rules, or sensitivity analyses.
The registry also does not identify an intention-to-treat or other analysis population for the primary endpoint. Therefore, the enrollment figure should not be assumed to equal the number included in any particular endpoint analysis. These omissions restrict evaluation of selective reporting, robustness to missing data, and the interpretation of any unreported comparisons.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Alprazolam | 0 | 7 | 0.0% |
| Dextroamphetamine | 0 | 7 | 0.0% |
| Placebo | 0 | 7 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Alprazolam | 0 of 7 |
| Dextroamphetamine | 0 of 7 |
| Placebo | 0 of 7 |
The adverse-event record lists alprazolam, dextroamphetamine, and placebo groups. For each listed group, 7 participants are recorded as at risk, with 0 serious adverse events and 0 other adverse events recorded as affecting participants. No serious adverse-event terms are listed. These are the registry’s recorded counts, not proof that no symptoms or events occurred outside the information submitted to the registry.
The study is crossover, so the same participants may have contributed to more than one condition. The at-risk entries should not be added to infer a count of distinct participants or treated as independent parallel groups. The registry does not report the collection procedures, observation period for adverse events, event definitions, or whether events were assessed after each condition.
Deaths are listed as null, which means they are not reported in the registry record; it should not be interpreted as a reported zero. The absence of recorded adverse events does not establish safety, especially when enrollment is limited and the record does not describe event ascertainment or follow-up. These entries allow only a narrow reading of what was recorded for the listed groups.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, double-blind crossover drug-challenge study designed to assess spectroscopic imaging of brain chemicals in healthy volunteers. Its primary endpoint is a time-specific measure of percent change in left-thalamus GABA relative to creatinine after an acute challenge. The record supplies an endpoint definition and measurement schedule, but not the endpoint results needed to evaluate the study’s stated measurement question.
Accordingly, the record does not establish whether alprazolam, dextroamphetamine, or placebo was associated with a particular direction or size of GABA change. It does not establish that the imaging method detected a reproducible response, or that response patterns differed by condition. The study’s hypothesis about unique spatial and directional metabolic patterns remains a hypothesis in the registry record.
This absence of posted results should be distinguished from a finding of no effect. Without estimates, uncertainty intervals, or a specified primary comparison, there is no basis in the record for concluding either that a difference exists or that the conditions are similar. The fact that the study is marked terminated also does not explain whether data were collected as planned or why the study ended.
Even if numerical results were available, a technical signal change would not automatically establish clinical benefit or harm. The study concerns acute measurements in healthy volunteers, and the record does not report patient outcomes or longer-term follow-up. Generalizing beyond the population and measurement context described would require evidence not reported in the registry record.
The most defensible interpretation is therefore limited: the registry describes the design, interventions, endpoint, and some adverse-event counts, but does not report the principal outcome findings. The study’s purpose and planned measures can be understood; its primary statistical result cannot be assessed from the registry information.
13. Why This Trial Matters Statistically
This study raises a useful statistical question about how to evaluate an imaging protocol when the intended signal is measured repeatedly after a challenge. A measurement method may produce values at several post-dose times, but a clear inferential target is needed to distinguish a time-course description from a single condition comparison. The record gives the measurement schedule and a primary endpoint definition, yet does not identify one comparison that summarizes the primary question.
The crossover design also illustrates why the unit of analysis matters. Participants can contribute measurements under more than one condition, so the observations are not automatically independent. Within-participant comparisons can be informative, but interpretation depends on condition order, carryover, period effects, and appropriate handling of repeated observations. These design and analysis details are not reported in the registry record.
The endpoint uses a relative change in GABA/Cr and reports a median with an inter-quartile range. That pairing emphasizes the distribution of measured changes, while leaving unanswered how uncertainty around a condition contrast would be quantified. Descriptive summaries and inferential estimates answer related but different questions. A readable statistical report would need to make both the target comparison and its uncertainty clear.
Finally, the study highlights that a registered hypothesis and detailed endpoint are not substitutes for posted results. Without the estimates, uncertainty, analysis population, and missing-data account, neither the performance of the imaging protocol nor the condition-specific response patterns can be judged. The record is informative about what was intended, while its statistical conclusions remain unreported.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record gives limited information for evaluating the study’s conduct and results. It lists enrollment as 7 and marks the study terminated, but does not report how many participants completed the crossover conditions or contributed to the primary endpoint. Reasons for termination are not reported in the registry record, so the status alone cannot explain the availability or completeness of results.
Important crossover details are absent, including the randomized condition sequence, washout arrangements, period effects, and carryover assessment. The record also does not describe who was masked, how masking was maintained, or whether it was assessed. These details matter for interpreting acute drug challenges and repeated measurements.
The primary endpoint is defined across multiple timepoints, but the registry does not identify a single primary contrast or report endpoint estimates. It does not describe the statistical model, adjustment for repeated measures, treatment of outlying or technically unusable spectra, or any multiplicity procedure. The sample-size justification and analysis population are not reported in the registry record.
Missing-data details are unavailable, including the amount and reasons for missing measurements and how incomplete crossover data were handled. The registry records no analysis details and gives no confidence interval or other measure of precision for the primary comparison. Without these elements, the robustness of any potential findings cannot be evaluated.
The study concerns healthy volunteers and acute imaging responses. The registry does not report clinical outcomes or longer-term observations, limiting the scope of any interpretation beyond the measurement question. These are limitations of the information reported in the registry; they do not establish what was or was not done outside that record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Spectroscopic Imaging at 4T: A Drug Challenge Study — NCT01577706.
- Registry record last updated 2017-04-04; status last verified 2017-03.
- Results first posted 2017-04-04.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01577706 is titled “Spectroscopic Imaging at 4T: A Drug Challenge Study.” The registry describes a randomized, double-blind crossover study in healthy volunteers, with alprazolam, dextroamphetamine, and placebo challenge conditions. Enrollment is listed as 7, the status is terminated, and the study phase is NA.
The primary endpoint concerns percent change in left-thalamus GABA relative to creatinine across post-dose measurement times. The record specifies the median and inter-quartile range but does not report primary endpoint values or a single condition comparison. It lists 7 outcome measures and 0 analyses.
For each intervention group, the adverse-event entry lists 7 at risk and 0 serious and 0 other adverse events affecting participants. Deaths are not reported. The registry does not report the analysis population, missing-data methods, detailed statistical plan, or reason for termination. Consequently, the record describes the study’s aims and design but does not permit assessment of its primary statistical findings.