Levetiracetam for the Treatment of Alcohol Dependence and Anxiety: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Levetiracetam for the Treatment of Alcohol Dependence and Anxiety (NCT00141115), a na phase 2 study. The primary outcome is Participants Who Reported Reductions in Alcohol Consumption.

2. Clinical Question

The study’s stated rationale was that anxiety, mood, and sleep disturbance accompanying reductions in alcohol use might make it difficult for people to reduce or discontinue drinking. The clinical question is therefore exploratory: whether reduced drinking was observed among participants receiving levetiracetam in this pilot setting. Without a control group and with only three enrolled participants, the record cannot isolate a treatment effect from other explanations for changes in drinking. It also does not report enough outcome information to describe the observed change.

3. Trial Design

This was a Phase 2 pilot trial, listed as completed, with a single-group model and an enrollment of 3. The intervention was levetiracetam 1500 mg twice daily. The registry lists allocation as not applicable and masking as none. These design features mean the study did not use a randomized treatment allocation or a blinded comparison. No like-for-like control group is described in the registry record.

The study focused on alcohol dependence with comorbid anxiety. The listed conditions include alcoholism and several anxiety diagnoses, while the brief summary refers more generally to patients with anxiety symptoms. The precise eligibility criteria, recruitment process, and characteristics of the three enrolled participants are not reported in the registry record. The sponsor was New York State Psychiatric Institute. The recorded study start was 2004-03 and primary completion was 2008-01.

The primary outcome was a participant count: the number drinking less at the end of the study than at the beginning. Its timeframe is described as over 9 weeks of study or length of participation. A secondary outcome was percent of drinking days. The record lists two outcome measures overall, but no analysis results. It does not report how drinking was assessed, how missing observations were handled, or whether all participants completed the planned observation period.

A single-group pilot can describe what was observed among those enrolled and can help identify practical questions for further study. It cannot by itself distinguish a medication-related change from changes due to time, study participation, variation in drinking, or other influences. The small enrollment also makes the experience of any individual participant consequential to the overall count. The registry record does not report a protocol-based sample-size justification, detailed statistical plan, or interim analysis plan.

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: Participants were enrolled under open-label conditions.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Number of participants who were drinking less at the end of the study compared to the beginning.

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 Participants Who Reported Reductions in Alcohol Consumption, measured over over 9 weeks of study or length of participation.

The primary endpoint counts participants who were drinking less at the end of the study than at the beginning. It is a binary outcome at the participant level: each participant either meets the stated reduction criterion or does not. The reported measure is the number of participants meeting that criterion, rather than the size of each person’s reduction.

A count can give a direct, easily understood description of how many enrolled participants met a prespecified outcome definition. In a pilot study, such a measure may help describe whether the outcome was observed and whether the measurement approach is usable. It does not, on its own, show how much drinking changed, how consistently it changed, or whether the change was caused by the intervention.

The registry specifies the comparison as drinking less at the end than at the beginning, over 9 weeks of study or length of participation. It does not report a threshold for what constitutes a reduction, the method used to collect drinking information, or the observed count. Those omissions limit interpretation: a reader cannot determine the magnitude or distribution of changes, nor assess the precision of an estimated treatment effect from this outcome. The endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as a count of participants who reported reductions in alcohol consumption. This is a binary participant-level outcome summarized as a count. General statistical explanation: binary outcomes classify each person according to whether a defined event or condition occurred. A count reports how many participants met the definition, but does not convey the size of a change within each participant.

What does the endpoint count?

The stated definition is the number of participants drinking less at the end than at the beginning. The timeframe is described as over 9 weeks of study or length of participation. The record does not specify a minimum amount of reduction, the source of the drinking information, or the precise assessment schedule. Without those details, a reader cannot assess the operational definition or reproduce the endpoint from the registry description alone.

A count can be informative as a straightforward description of participants meeting an outcome definition. Its interpretation depends on the number enrolled and on how the outcome was measured. Here, enrollment was 3, but the number meeting the primary endpoint is not reported in the registry record. No percentage or other transformation should be inferred from the count when the result is absent.

What can a single-group design estimate?

The study is listed as single-group, with no randomized allocation and no masking. A single-group before-and-after design can describe observed changes over time among enrolled participants. General statistical explanation: without a concurrent comparison group, it is not possible to determine whether changes would also have occurred without the intervention. Time trends, participant expectations, measurement effects, and other influences can be alternative explanations. These are general limitations of the design, not reported events in this trial.

Masking concerns whether participants or study personnel know which intervention is being received. The registry lists masking as none. For outcomes based on reported drinking, knowledge of treatment may be relevant to how information is reported or assessed. The record does not report procedures for reducing such influence, and no assumption should be made about how outcome collection was conducted.

What do statistical tests and intervals add?

General statistical explanation: a statistical test evaluates how compatible observed data are with a specified null hypothesis under a model and its assumptions. A confidence interval describes uncertainty around an estimated quantity, including values that remain compatible with the data and method. Neither replaces careful attention to design, measurement, and sample size. The registry record reports zero analyses and does not post a test, an effect estimate, or a confidence interval for the primary outcome.

A missing analysis result is not evidence that an outcome did not occur, and it is not evidence that a particular statistical test was negative. It means that the registry record does not provide a result to interpret. There is also no reported model specification, covariate adjustment, or method for handling repeated measurements. These analysis details are not reported in the registry record.

How should planning illustrations be read?

The assumptions accompanying the planning illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They state that the effect to detect is a fraction of the observed effect. The illustrations are planning scenarios, not the trial’s own design or evidence that the study had a particular probability of detecting an effect. They are not observed power.

Those assumptions describe a hypothetical two-arm design, whereas this trial is listed as single-group. Accordingly, such illustrations should not be mistaken for a direct analysis of the trial’s design or outcome. General statistical explanation: sample-size planning depends on the effect size considered important, outcome variability, the chosen error rate, allocation, and analysis method. The registry record does not report the study’s own sample-size justification or enough primary-outcome results to evaluate a trial-specific planning rationale.

General statistical explanation: over-dispersion occurs when outcome variability exceeds what a statistical model assumes. It can make model-based standard errors too small and intervals too narrow if the extra variability is ignored. The registry describes a participant count, but does not report a count model, a dispersion estimate, or an analysis that would permit an over-dispersion assessment. It would therefore be inappropriate to infer that such a model was used.

The secondary measure, percent of drinking days, could be summarized in several ways depending on the measurement and analysis plan. The registry record does not report those details or the secondary result. For both outcomes, the absence of posted analyses limits statistical interpretation to the stated design and outcome definitions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Levetiracetam 1500 mg Twice Daily")
n      <- c(3)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Levetiracetam 1500 mg Twice Daily  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary participant count for reduced alcohol consumption and the secondary outcome of percent of drinking days. It also lists zero analyses. No multiplicity adjustment, hierarchy among secondary outcomes, or approach to choosing among analyses is reported in the registry record.

General statistical explanation: when multiple outcomes or tests are considered, the chance of at least one apparently unusual result can increase if each is interpreted separately without accounting for multiplicity. A prespecified primary outcome can help focus interpretation, but the registry record does not report a detailed statistical analysis plan or how any secondary outcome would be interpreted relative to the primary endpoint. No claim can be made about adjustments that may have been made outside the record.

The record does not report how missing outcome information was handled, whether all enrolled participants contributed endpoint data, or whether the analysis population was defined as all enrolled participants or a subset. It also does not describe withdrawals, exclusions, or reasons for missing assessments. Those details are important because incomplete outcome data can affect both the count and its interpretation.

The enrollment of 3 does not itself establish whether any data were missing. The registry does not provide participant-level completion information, so missingness cannot be assessed. No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. The posted information therefore does not support a judgment about the impact of missing outcomes or the robustness of an analysis population.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

For the levetiracetam 1500 mg twice-daily group, the registry records 0 serious adverse events among 3 participants at risk and 0 other adverse events among 3 participants at risk. These are the safety counts recorded for this study. They describe the posted event reporting, not a comparison against another group.

A count of zero in a small study should be read narrowly. It means that the registry record lists no events in the specified categories among the participants at risk; it does not establish that an event is impossible or that a broader population would have the same experience. General statistical explanation: sparse safety data provide limited information about the range and frequency of possible harms, particularly when there is no comparator and the number observed is small.

Deaths are not reported in the registry record. The record lists no top serious adverse event terms. The duration and completeness of safety monitoring, the method used to collect events, and any criteria for classifying an event as serious are not reported in the registry record. The recorded zero counts should therefore not be extended beyond the categories and participants documented.

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

This registry entry describes a pilot study asking whether reduced drinking was observed among participants with alcohol dependence and anxiety symptoms who received levetiracetam. It records a single-group design, no masking, an enrollment of 3, and a primary endpoint based on the number drinking less at the end than at the beginning. It does not report the primary endpoint result or statistical analyses.

The absence of a posted result is not a zero result. It does not mean that no participant reduced drinking, and it does not mean that every participant did. The registry record does not provide the count needed to answer that question. Likewise, the absence of an inferential analysis does not support a conclusion about statistical significance or the size of an effect.

Even if a before-and-after result were available, the single-group design would not by itself establish that levetiracetam caused any observed change. General statistical explanation: treatment effects are most clearly separated from background change when an appropriate comparison is available and the analysis is designed to address relevant sources of bias. No such comparison is described in this study.

The enrollment of 3 also limits how much can be learned about the variety of outcomes in a broader population. A pilot can be useful for describing feasibility or generating questions, but the registry record does not report feasibility measures, participant-level outcome details, or a formal plan for a later study. The secondary outcome result is also not reported.

Accordingly, the record supports a description of the study’s purpose, design, and listed outcome definitions, but not a conclusion that treatment was effective or ineffective. It also does not establish the absence of risk. The posted safety counts are limited to the categories and participants recorded and are not a substitute for a comparative safety assessment.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated exploratory question and the limited outcome information available in the registry record. The primary endpoint is understandable as a participant count, but without the observed count there is no result to quantify. A statistical interpretation must distinguish an unreported outcome from an observed outcome of zero.

The single-group design is important because it limits causal interpretation independently of sample size. A before-and-after change, even if reported, would not distinguish treatment-associated change from other influences without a comparator. This makes the study useful to read as a pilot record, rather than as a controlled estimate of a treatment effect.

The enrollment of 3 further illustrates why descriptive counts and uncertainty need context. In a very small sample, an individual participant’s outcome has substantial influence on the group description. That general feature does not allow reconstruction of the missing result; it emphasizes why participant-level information and transparent reporting matter.

The record also lists a secondary outcome, percent of drinking days, without results, and reports zero analyses. This leaves unanswered whether and how outcomes were analyzed, whether missing observations affected the endpoint, and whether more than one analysis was considered. These are practical reporting questions, not grounds to assume a particular analysis took place.

For clinical researchers and biostatisticians, the entry highlights the value of aligning design, outcome definition, and reporting. A precise endpoint definition, a clearly described analysis population, transparent handling of missing data, and complete outcome results are needed to evaluate even an exploratory study. The record’s limitations should be treated as limits on interpretation, rather than as evidence for or against a treatment effect.

15. 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 the enrollment of 3 in a single-group design. No randomized comparison is recorded, so the study cannot provide a controlled contrast between levetiracetam and another condition. Masking is listed as none, which is relevant to interpreting an outcome based on reported drinking. These design characteristics constrain causal conclusions regardless of any unreported result.

The primary outcome description does not specify the minimum reduction that qualifies a participant as drinking less, how drinking was measured, or how the beginning and end assessments were scheduled. The timeframe is stated as over 9 weeks of study or length of participation, but individual exposure and follow-up are not described. The observed primary result is not reported in the registry record.

The registry lists percent of drinking days as a secondary outcome, but does not report its result. It lists two outcome measures and zero analyses. Detailed statistical methods, an analysis population, a sample-size justification, a multiplicity strategy, and missing-data methods are not reported in the registry record. Participant characteristics, adherence, withdrawals, and outcome completeness are also not described in the information recorded.

Safety information is limited to the listed event counts among the participants at risk. Deaths are not reported, and monitoring duration and event-collection procedures are not described. The registry entry therefore offers only a narrow account of safety and efficacy-related outcomes, and does not support broad conclusions beyond its documented design and records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Levetiracetam for the Treatment of Alcohol Dependence and Anxiety — NCT00141115.
• Registry record last updated 2019-04-24; status last verified 2019-04.
• Results first posted 2017-09-15.
• 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.

19. Record Summary

The registry record identifies NCT00141115 as a completed Phase 2 pilot trial of levetiracetam for alcohol dependence with comorbid anxiety. It lists a single-group, unmasked design, allocation not applicable, enrollment of 3, and levetiracetam 1500 mg twice daily. The recorded start was 2004-03 and primary completion was 2008-01; the sponsor was New York State Psychiatric Institute.

The primary outcome was the count of participants drinking less at the end than at the beginning, over 9 weeks of study or length of participation. Percent of drinking days was listed as a secondary outcome. The primary result and secondary result are not reported in the registry record, and zero analyses are listed. Safety records list 0 serious adverse events and 0 other adverse events among 3 participants at risk; deaths are not reported.

The single-group design, absence of masking, small enrollment, and missing outcome analyses limit interpretation. The record describes the study question and design, but does not provide a treatment-effect estimate or a comparative assessment.