Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving (NCT01822587), a randomized phase 2 study. The primary outcome is Cocaine Use.

2. Clinical Question

The study’s stated rationale is to test whether propranolol following cocaine-cue exposure can be used to alter drug-associated memories and reduce craving, cue reactivity and cocaine use. It also describes an expectation that effects could be greater with 80 mg than with 40 mg. These statements describe the investigators’ rationale and expectations, not trial findings. The posted primary outcome is cocaine use; craving and cue reactivity appear in the study summary but are not identified as the primary endpoint in the record. The record does not report a numerical result for any of these outcomes.

3. Trial Design

The registry describes NCT01822587 as a Phase 2, randomized, triple-masked, parallel trial, with an enrollment of 181. The sponsor is the Medical University of South Carolina. The condition listed is Cocaine Addiction. The trial began in 2013-09, had a primary completion date of 2018-11-05, and is recorded as completed.

There are three intervention groups: placebo, propranolol 40 mg, and propranolol 80 mg. The arm descriptions state that each intervention was administered once orally after cue exposure on each of the first two days of testing. The record does not report the allocation ratio, the method used to generate or conceal assignments, or which people were masked under the triple-masking designation. It also does not report whether adherence to the assigned intervention was assessed.

A parallel design assigns participants to a group whose intervention is compared with the interventions assigned to other groups. In general, randomization is intended to make assigned groups comparable with respect to factors that could influence an outcome, while masking can limit influences on treatment delivery, outcome assessment, or reporting. Those are general purposes of these design features; the record does not specify how they were implemented in this trial.

The primary outcome is described as the mean dollar amount of cocaine use, evaluated at Weeks 1, 3 and 6. Although the study summary discusses cue exposure and follow-up cue exposures, the precise schedule and procedures beyond the arm descriptions are not reported in the registry record. Eligibility criteria, recruitment setting, baseline characteristics, and the analysis population are also not reported. The enrollment figure should therefore be read as the recorded enrollment, not as evidence about how many participants contributed data to each outcome assessment.

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.

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 Cocaine Use, measured over Evaluated at Weeks 1, 3 and 6.

The primary endpoint is cocaine use expressed in dollar amounts. The record describes it as a continuous measure summarized by a mean, with standard error as the dispersion measure. It says the outcome was evaluated at Weeks 1, 3 and 6 and describes the measure as the timeline of cocaine use during the study.

As a general statistical matter, measuring use in dollar amounts gives a quantitative way to represent reported cocaine use over the specified assessment periods. A mean describes the central value of a set of measurements, while a standard error describes the precision of an estimated mean, rather than the spread of individual participants’ values. The record does not explain how dollar amounts were elicited, what recall period was used, whether zero use was handled in a particular way, or how these amounts relate to the quantity of cocaine used.

The repeated assessment weeks make the timing of measurement important: a result at one assessment is not automatically a result at another. The registry record does not report a single combined endpoint across the assessment weeks, a prespecified contrast between groups, or numerical means and standard errors. It therefore does not permit a reader to judge the size or precision of any treatment-group difference in cocaine use from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, triple-masked, parallel Phase 2 trial. These design labels describe how a trial is organized, but do not themselves establish what the results were. The record does not report the detailed statistical analysis plan, the method of randomization, the masking roles, or the model used for the primary outcome. The explanations below describe general statistical ideas and distinguish them from what is documented for this trial.

What does randomization contribute?

In general, randomization uses an assignment process intended to balance measured and unmeasured prognostic factors across groups on average. This supports comparisons based on assigned intervention, provided the analysis and follow-up preserve the intended comparison. Randomization does not guarantee exact balance in a particular trial, and a group comparison can still be affected by missing data, non-adherence, or analysis choices. The record identifies random allocation but does not report the assignment method, allocation ratio, or a baseline comparison of the groups.

What does masking mean?

Triple masking is the designation in the registry. Masking is generally used to reduce the chance that knowledge of an assigned intervention affects care, assessment, or reporting. The record does not identify which parties were masked, how masking was maintained, or whether it was assessed. It is not possible to infer these operational details from the label alone.

How should a mean and standard error be read?

The primary endpoint is continuous: dollar amounts of cocaine use, summarized as a mean with standard error. In general, a mean is an average across observations. The standard error describes uncertainty in an estimated mean and is not the same as the range or variability of individual observations. A confidence interval, when reported, uses an estimate and its uncertainty to give a range of values compatible with the data under the method’s assumptions. No primary-outcome means, standard errors, or confidence intervals are reported in the registry record, so none can be interpreted for this trial.

Why can repeated assessments complicate analysis?

The outcome is evaluated at Weeks 1, 3 and 6. Repeated measurements on the same participant are generally related, so an analysis may need to account for within-person dependence. Investigators might analyze each assessment separately or use a model that incorporates the repeated observations; those approaches answer different questions and require explicit assumptions. The registry record does not state which approach was planned or used, how a primary time point was selected, or whether a combined longitudinal effect was intended. It is therefore not appropriate to infer a model from the outcome schedule.

Why do distribution and model assumptions matter?

In general, a continuous outcome can have a distribution that differs from the assumptions of a simple mean-based model. Dollar amounts may also include many zero values or observations far from the center, but the record does not describe the observed distribution, so it cannot be said that either feature occurred in this trial. If a distribution has greater variability than a model allows, standard errors can be too small and uncertainty can be understated; this is one reason analysts examine fit and consider methods suited to the data. No distributional checks, transformations, robust methods, or model diagnostics are reported.

What role do confidence intervals and p-values play?

In general, a confidence interval communicates the uncertainty around an estimated contrast, while a p-value measures how incompatible the observed data are with a specified null model under stated assumptions. Neither quantity alone describes clinical importance. A narrow interval can indicate greater precision than a wide interval, while an estimate’s magnitude and the interval’s range are needed to understand what effects remain plausible. The registry record contains no primary contrast, interval, or p-value, so statistical significance and precision cannot be assessed.

What do the planning assumptions mean?

The sample-size planning description states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that a particular sample size was required or that the trial achieved a particular probability of detecting an effect. The record does not report the calculated planning counts or the trial’s own sample-size justification. Planning illustrations are not observed power, and they should not be interpreted as the probability that the trial’s finding is true.

The planning description also distinguishes participant counts per arm from total event counts for time-to-event outcomes. The primary endpoint in this trial is continuous, not described as time-to-event. The record provides no effect estimate or numerical planning illustration with which to assess the assumptions. It also does not report interim analyses, adjustments for multiple testing, covariates, analysis sets, or missing-data methods. These methods details should not be inferred from the design labels or the study summary.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is measured at Weeks 1, 3 and 6, and the registry notes that the outcome has several categories or time points and was not reduced to one comparison. The record also lists five outcome measures. These features create potential multiplicity questions: when several outcomes, time points, or group contrasts are examined, the chance of at least one apparently unusual result can increase if each is assessed independently. General approaches include prespecifying a primary contrast, adjusting inference across a family of tests, or treating secondary findings as exploratory. The registry does not report which, if any, approach was planned or used.

There are three intervention groups, but the record does not identify the primary pairwise comparison, whether both propranolol doses were to be compared with placebo, or whether the doses were to be compared with each other. No multiplicity adjustment, hierarchy of outcomes, or testing strategy is reported. Without the analysis plan and numerical results, neither the intended family of comparisons nor the consequences of multiple testing can be assessed.

The record does not report the number of participants with outcome data at each week, reasons for missing measurements, or methods for handling missing data. In general, missingness can affect estimates when the chance of having an observed measurement is related to a participant’s outcome or characteristics. Analyses that use only observed measurements and methods that model or impute missing values rely on different assumptions. The record does not say which method was used, whether sensitivity analyses were performed, or whether missingness differed among groups.

The analysis population is also not reported. The registry does not state whether analyses followed assigned groups, included only participants who completed treatment, or used another population definition. Those choices can affect interpretation, particularly when assignment and treatment actually received differ. No conclusions about the analysis population or missing-data robustness can be drawn from the enrollment figure alone.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events and other adverse events separately for the three groups. For serious adverse events, the recorded number affected is 0 in placebo, 0 in propranolol 40mg, and 0 in propranolol 80mg. The corresponding numbers at risk are 59, 60 and 62. Deaths are recorded as 0 in each group.

For other adverse events, the number affected is 0 in placebo, 1 in propranolol 40mg, and 0 in propranolol 80mg. The numbers at risk are 59, 60 and 62, respectively. These are counts as recorded, not a full account of the type, timing, severity, or duration of events. The registry does not provide terms for the recorded other adverse event or serious adverse event terms.

In general, a count of zero means that no event was recorded in the relevant category and group in this registry entry; it does not establish that the underlying risk is absent. Small event counts also provide limited information about differences between groups. The registry record does not report statistical comparisons, adjudication details, or whether the event counts were assessed over identical follow-up. The figures should therefore be read descriptively, without attributing an event to an intervention or treating the group counts as proof of a safety difference.

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

The record establishes that a completed randomized, triple-masked, parallel Phase 2 trial was registered to study propranolol after cocaine-cue exposure, with placebo and two propranolol dose groups. It identifies cocaine use, measured in dollar amounts at Weeks 1, 3 and 6, as the primary outcome. It also records the enrollment, intervention descriptions, and adverse-event counts.

It does not establish whether propranolol changed cocaine use, craving, cue reactivity, or any other outcome. The study summary states what investigators expected, but expectations are not results. No numerical outcome findings, between-group estimates, confidence intervals, or p-values are reported. Consequently, the size and direction of any effect, and the precision with which it may have been estimated, cannot be determined from the registry record.

Nor does the absence of a reported efficacy result mean that the interventions had no effect. It means that the registry entry does not give the information needed to judge the outcome. Similarly, the absence of recorded serious adverse events is a descriptive observation in this record, not proof that serious events could not occur or that the groups had equivalent safety.

Even a reported difference in a trial outcome would need interpretation in light of the analysis population, missing data, measurement procedures, and statistical plan. Those details are not reported in the registry record. The enrollment total and completion status do not substitute for outcome estimates or show how many participants contributed data at each assessment.

The appropriate conclusion is therefore about the available evidence in the record, not about treatment efficacy: the trial’s design and outcome definition are documented, but the posted results do not permit a statistical conclusion about its primary clinical question.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named endpoint is not the same as an interpretable result. The registry identifies a continuous primary outcome, its units, its summary measure, and its assessment weeks. Those details help define what the investigators intended to measure. Without group estimates and an analysis contrast, however, they do not answer whether the groups differed or how uncertain any difference might be.

The three-group design and repeated outcome assessments also show why the analysis plan matters. Comparisons among placebo and two doses, across multiple weeks and several outcome measures, can create more than one plausible statistical question. Prespecification and transparent reporting help readers distinguish the primary test from secondary or exploratory analyses. The registry does not provide that testing strategy, so it cannot establish which comparison was decisive or how multiplicity was addressed.

The distinction between a mean and its standard error is another useful statistical point. A mean describes the estimated average, while its standard error concerns precision; neither alone conveys the full distribution of individual outcomes. For a measure expressed in dollar amounts, details about measurement, the distribution, and the model are important to understand what an average represents. Those details are not reported in the registry entry.

Finally, completion status, enrollment, and safety counts answer different questions from efficacy estimates. A completed trial can still have no results recorded for its primary endpoint, and a zero event count is not a comparative analysis. This record is therefore a useful example of how design information can be present while the results needed for statistical interpretation remain unavailable.

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 main trial-specific limitation is that the registry does not report numerical results for the primary outcome. There are no group means, standard errors, treatment contrasts, confidence intervals, or p-values with which to assess the pattern or precision of cocaine-use measurements. Although the primary outcome is specified at Weeks 1, 3 and 6, findings at those assessments are not given.

The record also does not report results for craving, cue reactivity, cocaine use during follow-up cue exposures, or other outcomes mentioned in the study summary. It lists five outcome measures but does not give their names or findings in the information recorded. No analysis results are listed. The summary’s predicted benefits should not be mistaken for observed results.

Important design and analysis details are absent, including eligibility criteria, participant characteristics, allocation ratio, the parties masked, outcome measurement procedures, and the analysis population. The record does not describe the model, how repeated assessments were handled, how missing data were treated, or whether the analysis followed assigned groups. It also does not report a statistical testing hierarchy, multiplicity adjustment, interim analyses, or the trial’s own sample-size justification.

The safety record gives counts but no event descriptions for the other adverse event and no serious adverse event terms. It does not provide context about event timing, duration, relatedness, or follow-up completeness. These limitations restrict the interpretation of safety counts as well as efficacy findings. The trial is recorded as completed, but completion alone does not resolve the missing detail or supply outcome estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving — NCT01822587.
• Registry record last updated 2019-12-26; status last verified 2019-12.
• Results first posted 2019-12-17.
• 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

NCT01822587, titled “Enhancing Disrupted Reconsolidation: Impact on Cocaine Craving,” is recorded as a completed Phase 2 randomized, triple-masked, parallel trial sponsored by the Medical University of South Carolina. Its enrollment is 181, and the condition listed is Cocaine Addiction. The record gives a start date of 2013-09 and a primary completion date of 2018-11-05.

The three groups received placebo, propranolol 40 mg, or propranolol 80 mg, described as oral administration after cue exposure on each of the first two testing days. The primary outcome is mean dollar amounts of cocaine use, evaluated at Weeks 1, 3 and 6. The registry does not report numerical primary-outcome results or a statistical comparison. Serious adverse events and deaths are recorded as 0 in all groups; one other adverse event is recorded in the propranolol 40mg group.