Repurposing alpha1 Noradrenergic Antagonists for Alcoholism Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Repurposing alpha1 Noradrenergic Antagonists for Alcoholism Treatment (NCT02966340), a randomized phase 1, phase 2 study. The primary outcome is Startle Potentiation During Stress Reactivity Task..

2. Clinical Question

This is a laboratory stress-reactivity question, not a direct measure of alcohol consumption or a clinical treatment outcome. The primary endpoint is titled “Startle Potentiation During Stress Reactivity Task.” Its description says the reported measure is the point estimate of an effect from an unadjusted general linear model, with a 95% confidence interval. Numerical estimates and interval limits are not reported in the registry record.

The study also lists self-reported anxiety potentiation during the task as a secondary outcome. Numerical results for that outcome are not reported in the registry record. The listed timeframe for the primary endpoint is 7 days; further details about how that timeframe relates to visits, task measurements, or outcome aggregation are not reported in the registry record.

The relevant statistical question is therefore whether the registered task response differs across the prazosin and placebo conditions, and how precisely any such contrast is estimated. Because the numerical outcome results are not reported, the direction, magnitude, and uncertainty of the primary contrast cannot be described. The record also does not establish whether any observed task response would correspond to a change in drinking or other outcomes outside the laboratory.

3. Trial Design

The registry describes a randomized, triple-masked, crossover study in Phase 1 and Phase 2. Its brief summary calls the design double-blind and placebo-controlled, while the masking field labels it triple. The roles covered by the masking label are not reported in the registry record, so the two descriptions cannot be reconciled from the record alone.

The treatment conditions are prazosin and placebo. The arm descriptions state that all participants receive 2mg prazosin and placebo in a crossover, with the order counterbalanced between participants: one sequence starts with prazosin and the other starts with placebo. This describes treatment order, not separate parallel groups receiving only one condition. The registry does not report further details about the interval between visits, any washout period, or how period and sequence effects were handled analytically.

Enrollment is 70. The record lists the study as completed, with a start date of 2016-11-01 and a primary completion date of 2018-03-12. These registry entries do not establish how many participants completed both conditions or contributed to each outcome; those analysis-population counts are not reported in the registry record.

The primary endpoint concerns startle potentiation during an NPU stressor task. The description compares startle responses in unpredictable-shock and predictable-shock conditions with responses in a no-shock condition. The primary timeframe is listed as 7 days. The registry also lists self-reported anxiety potentiation during the task as a secondary outcome.

The endpoint description says that point estimates came from unadjusted general linear model analyses with 95% confidence intervals. Specific model terms, treatment of the crossover structure, and handling of visit order are not reported in the registry record. Numerical estimates for the primary and secondary outcomes are also not reported. Consequently, the design features can be described, but their relationship to the observed endpoint estimates cannot be evaluated from the posted results.

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.

Before assignment: In order to enroll 64 participants with valid data, 70 participants were randomized to account for 4 lost early in study flow (one data collection error, two startle non-responders, and one withdrawn after visit 1).

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Startle Potentiation During Stress Reactivity Task., measured over 7 days.

The primary endpoint is startle potentiation during a stress-reactivity task, measured in μV. The description defines the task contrast through startle responses during unpredictable-shock and predictable-shock conditions, compared with the no-shock condition. This measures a physiological response in a controlled laboratory context, rather than a direct measure of drinking behavior or longer-term clinical status.

Startle response is used in this setting as an outcome related to reactivity during a stressor task. In general, comparing responses across task conditions can help describe whether the measured response varies with the type of anticipated or absent shock condition. A treatment-condition contrast can then address whether the task measure differs between the prazosin and placebo conditions, subject to the analysis used.

The registry describes the endpoint as a mean of a continuous measure and says that the reported point estimate is from an unadjusted general linear model analysis, with a 95% confidence interval. General linear models can express a contrast in the mean outcome while accounting for the model terms that are specified. The record does not report the specific terms used or numerical endpoint estimates and interval limits.

The primary outcome is described across several categories or time points and is not reduced to a single comparison in the posted result summary. The component estimates and the way those categories or time points relate to one another are not reported in the registry record. Without those details and the numerical results, the endpoint definition can be understood, but the observed pattern and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure, and the registry describes it as a mean with a 95% confidence interval. It also states that the point estimate came from an unadjusted general linear model. The following concepts explain how such methods are generally used; they do not establish details beyond those stated in the registry record.

What does a mean contrast represent?

For a continuous outcome, a mean is a measure of the central level of the recorded values. A contrast between conditions expresses how the modeled mean differs between them, on the outcome’s original scale or on a scale defined by the model. Here the outcome is startle potentiation in μV. The registry does not give the numerical means or contrast, so neither the size nor direction can be interpreted.

A general linear model relates an outcome to explanatory terms chosen by the analyst. Depending on the model specification, those terms may represent treatment condition or other design features. The endpoint description calls the reported analyses unadjusted, but does not enumerate terms, state how repeated observations were represented, or explain how the crossover sequence was handled. The label alone does not show whether the analysis accounts for all relevant features of the study design.

What does a confidence interval tell the reader?

In general, a confidence interval is an interval estimate that conveys the uncertainty associated with a point estimate under the assumptions of the statistical method. It helps readers assess precision: intervals that are more concentrated around an estimate convey more precision than intervals that extend across a broader range. An interval does not by itself identify the cause of an outcome or establish clinical importance. It also does not remove limitations in the design or analysis.

The record specifies 95% confidence intervals for the primary outcome, but does not report their endpoints. Without the estimate and interval, it is not possible to judge the plausible range of the contrast, how precisely it was estimated, or whether the interval includes values that may matter scientifically. The same caution applies if a reader is considering the listed secondary outcome, for which numerical results are also not reported.

Why does the crossover structure matter?

In general, a crossover design exposes participants to more than one condition in a planned sequence. Because measurements from the same participant can be related, analyses commonly need to account for that within-participant dependence. The order in which conditions occur can also matter if outcomes change over time, if one period influences a later period, or if conditions have effects that persist. These are general statistical considerations, not claims that any such effects occurred in this study.

The registry describes counterbalanced order and a crossover, but does not report an analysis specification addressing within-participant correlation, period effects, sequence effects, or carryover. It would be inappropriate to assume that any particular correction or model was used. The endpoint description’s reference to an unadjusted general linear model does not provide enough detail to determine how these design considerations were addressed.

How should the planning assumptions be read?

The registry includes assumptions for a planning illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. The instructions distinguish participants per arm for non-time-to-event outcomes from total event counts for time-to-event outcomes. These are planning assumptions, not evidence about the observed results or a description of the trial’s own sample-size justification.

Numerical planning values and the observed effect used to generate them are not reported in the registry record. A planning illustration is conditional on its assumptions; it is not observed power and cannot substitute for the estimate and confidence interval from the trial. The trial’s sample-size justification and any protocol-specific power calculation are not reported in the registry record.

What can be concluded from the analysis description?

The record names an unadjusted general linear model and a 95% confidence interval, but does not give the model equation, the outcome estimates, the interval limits, or inferential test results. It lists no analysis entries, while the endpoint description refers to analyses; the actual numerical analysis results are not reported in the registry record. Without those details, the statistical method can be described at a broad level, but its implementation and conclusions cannot be independently evaluated.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of startle potentiation and a secondary outcome of self-reported anxiety potentiation during the stress-reactivity task. The primary outcome description covers several categories or time points and is not reduced to one comparison. That creates a need to understand which contrasts were intended to be primary and how conclusions across the outcome components were to be interpreted. The relevant hierarchy and any multiplicity strategy are not reported in the registry record.

In general, evaluating multiple outcomes or multiple contrasts can increase the chance of obtaining an apparently notable result by chance if each is assessed independently. Statistical approaches to multiplicity can include prioritizing a prespecified contrast or adjusting inference across a defined family of comparisons. This is a general consideration, not a statement about what was done in this study. The registry does not report an adjustment, a testing hierarchy, or an analysis plan for the listed primary and secondary outcomes.

Missing-data handling is also not reported in the registry record. The enrollment is 70, but the numbers contributing observations to each outcome, the extent of missingness, and any method for handling missing measurements are not provided. The record does not specify whether analyses used all randomized participants, participants with available measurements, or another defined analysis population.

For a crossover study, the completeness of measurements across both treatment conditions can affect which within-participant comparisons are available. The record does not report completion by visit or condition, or how incomplete crossover data were handled. Without those details, the potential influence of missing outcome data on the estimated contrast cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists adverse events separately for “Prazosin 2mg Trials” and “Placebo Trials.” For serious adverse events, each group has 64 at risk, 0 affected, and 0 deaths. For other adverse events, each group has 64 at risk; 30 are listed as affected in the prazosin trials and 3 in the placebo trials. These are the posted counts and should not be converted into percentages or treated as outcome estimates for the stress task.

The labels distinguish serious events from other adverse events. A count of 0 serious events in these groups does not establish that no safety concerns are possible, and the record does not provide event descriptions for the non-serious counts or causal assessments. It also does not report further details on event collection, severity categories beyond the serious-versus-other distinction, or the relationship between adverse events and treatment exposure.

The study uses a crossover, and the adverse-event groups are named as trial conditions. These figures should be read as registry-recorded group counts; they do not establish how many unique participants experienced an event across conditions. No total across groups should be inferred from these data. The safety counts do not establish efficacy or explain the primary endpoint results.

12. What the Result Does, and Does Not, Mean

The record describes a randomized, masked crossover comparison of prazosin and placebo in a laboratory stressor task, among a study population associated with alcoholism. Its primary outcome is startle potentiation across shock-related task conditions, and its secondary outcome is self-reported anxiety potentiation. These details define the scientific question and the kind of measurement used.

What the record does not establish is the numerical treatment contrast on the primary outcome. Estimates and 95% confidence interval limits are not reported in the registry record. The direction, magnitude, and precision of any observed difference therefore cannot be stated. Numerical secondary-outcome results are likewise not reported. This absence should not be interpreted as evidence of no difference or as evidence of a particular effect.

Even if a task contrast were reported, a laboratory stress-reactivity measure would not by itself answer whether alcohol consumption or other clinical outcomes changed. The registry does not report a direct drinking outcome in the listed primary or secondary outcomes. Any relationship between the task measure and outcomes outside the laboratory would require evidence not contained in this record.

Likewise, statistical significance and clinical importance are distinct concepts. In general, a statistical estimate describes a contrast under an analysis model, while its practical meaning depends on the outcome scale and the context in which the measure is used. Here, the numerical estimate, interval, and contextual threshold for interpreting the task measure are not reported in the registry record. No conclusion about clinical importance can be drawn from the endpoint description alone.

The adverse-event counts provide a separate, limited description of recorded safety events in the two trial conditions. They do not fill the gap in primary-outcome results, and they do not establish the effect of treatment on stress reactivity. A balanced reading is that the registry records the study design, outcome definitions, and adverse-event counts, but does not report enough numerical outcome information to assess the primary or secondary efficacy contrasts.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a crossover design applied to a laboratory measure. In general, crossover designs can compare conditions within participants, which may help account for stable differences between people. That potential benefit depends on the design and analysis appropriately addressing the relationship between repeated observations and the sequence of conditions.

The record explicitly describes counterbalanced treatment order and identifies both prazosin and placebo conditions. This makes period, order, and within-participant dependence important considerations when reading the analysis. The registry describes unadjusted general linear model analyses, but does not provide sufficient model details to determine how those design features were treated. The distinction between design description and analysis description matters: a crossover label does not alone establish that the statistical model accounts for the crossover structure.

The endpoint also illustrates why precise outcome definitions matter. Startle potentiation is defined through responses to unpredictable and predictable shock relative to no shock. The record states that the primary outcome spans several categories or time points rather than presenting a single reduced comparison. Interpretation therefore depends on the component estimates, their uncertainty, and the planned way of drawing conclusions across them. Those numerical details are not reported in the registry record.

Finally, the record distinguishes a statistical endpoint from a clinical outcome. A laboratory response may address a mechanistic or task-based question, but it is not interchangeable with a direct measure of behavior or longer-term clinical status. The available record permits readers to identify the design and measurement, while the absence of posted numerical outcome results limits assessment of the estimated effects and their precision.

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.

Participant eligibility criteria, baseline characteristics, and other details needed to understand who entered the study are not reported in the registry record. Enrollment is 70, but this does not establish how many participants completed both treatment conditions or contributed to the primary analysis. Counts for completed visits and outcome-specific analysis populations are not reported.

The primary outcome is described across several categories or time points, but the numerical component results and any combined summary are not reported. The endpoint timeframe is listed as 7 days, while details about measurement timing, task administration, and the relation between visits and the timeframe are not reported in the registry record. Numerical results for the secondary anxiety outcome are also not reported.

Although the study is described as randomized, triple-masked, and crossover, the masking roles and additional sequence procedures are not reported. The brief summary uses the term double-blind, and the record does not explain the relationship between that phrase and its triple-masked designation. A washout interval, if any, is not reported. The model description does not specify how within-participant dependence or period, order, and carryover effects were handled.

The registry does not report missing-data methods, prespecified analysis populations, a multiplicity strategy, or the analysis plan in enough detail to evaluate them. It also does not provide numerical primary-outcome estimates, confidence interval limits, or numerical secondary-outcome results. These omissions limit interpretation of the treatment contrast, its precision, and the robustness of any statistical conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Repurposing alpha1 Noradrenergic Antagonists for Alcoholism Treatment — NCT02966340.
• Registry record last updated 2019-05-28; status last verified 2019-05.
• Results first posted 2019-05-28.
• 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.

18. Record Summary

The registry record describes a completed randomized crossover study of prazosin and placebo for a laboratory stress-reactivity task, listed in Phase 1 and Phase 2. Enrollment is 70. The record lists the study start date as 2016-11-01 and primary completion date as 2018-03-12.

The primary outcome is startle potentiation during the stress-reactivity task, measured in μV, with a 95% confidence interval specified. The secondary outcome is self-reported anxiety potentiation during the task. Numerical results for these outcomes are not reported in the registry record. The endpoint description refers to unadjusted general linear model analyses, but detailed model specifications are not reported.

For adverse events, the record lists 0 serious adverse events and 0 deaths in each condition group. Other adverse events are listed for 30 in the prazosin trials and 3 in the placebo trials. These counts are separate from the unreported primary outcome estimates.