Effect of Endotoxin on Alcohol Consumption: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Endotoxin on Alcohol Consumption (NCT04527185), a randomized phase 2 study. The primary outcome is Alcohol Consumption.

2. Clinical Question

The registry summary describes the study as a pilot intended to collect human laboratory data on the effect of endotoxin on drinking behavior. The outcome therefore addresses consumption in a controlled session, rather than alcohol use across everyday settings. The registry record identifies Alcohol Consumption as the primary outcome and specifies a mean as the summary measure. It does not identify a separate primary analysis population or describe how the primary comparison was to be conducted.

3. Trial Design

This was a phase 2, randomized, quadruple-masked, parallel-group trial sponsored by Yale University. The registry record lists the trial as completed. Its recorded start date is 2022-02-27 and its primary completion date is 2024-10-31. The enrollment listed in the record is 27.

Participants were assigned to an Endotoxin group or a Placebo group. The Endotoxin arm description specifies a single administration of 0.4ng/kg i.v. during the laboratory session. The Placebo arm description also specifies a single administration during that session. The record identifies the trial as randomized but does not report the randomization procedure, allocation ratio, or method used to conceal the assignment sequence.

Quadruple masking indicates that the trial is recorded as having four masked roles, but the registry record does not identify those roles or describe how masking was maintained. It also does not report whether the success of masking was assessed. These details matter when interpreting a laboratory outcome, because participant expectations and researchers’ knowledge of assignment can affect how a session is conducted or reported. The record’s design labels alone do not establish how those issues were handled.

The parallel-group designation means that the listed groups are separate treatment arms, rather than a description of participants crossing between conditions. The registry record does not report the timing of randomization relative to the session, eligibility criteria, recruitment methods, or other protocol details that would clarify who was represented by the posted results. It describes the study as a pilot investigation of endotoxin and drinking behavior in a human laboratory. No broader conclusion about alcohol consumption outside the laboratory follows from that setting alone.

The outcome summaries are reported for 7.0 participants in the Endotoxin arm and 6.0 in the Placebo arm. The record does not explain why these group counts are smaller than the enrollment of 27, or whether all enrolled participants were randomized, received their assigned condition, or contributed data to the primary outcome. Participant flow and reasons for any unavailable outcomes are not reported in the registry record.

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 randomly assigned to endotoxin or placebo prior to the lab session.

Overall Study

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 Alcohol Consumption, measured over 120 minutes.

The primary endpoint is mean alcohol consumption, measured in milliliters during a 120-minute alcohol self-administration session. The registry describes the endpoint as the mean amount consumed for the Endotoxin and Placebo groups during that session. It is a continuous outcome: participants’ consumption can take different measured values, and the group result is summarized by a mean and a standard deviation.

The endpoint is used to quantify drinking behavior under the study’s laboratory conditions. A mean gives a group-level summary of the measured amounts, while the standard deviation describes how spread out the individual observations are around that group mean. The standard deviation is not a measure of the precision of the mean, and it does not provide the full distribution of participant-level outcomes.

The registry reports a mean of 37.57 milliliters and a standard deviation of 47.27 for the Endotoxin group, with 7.0 participants. For the Placebo group, it reports a mean of 50.08 milliliters and a standard deviation of 37.58, with 6.0 participants. The registry record does not provide confidence intervals, individual observations, or an inferential test for this endpoint. It also does not report additional endpoint details such as how consumption was measured or how incomplete sessions were handled.

Because the measure comes from a time-limited laboratory session, it describes consumption in that setting and timeframe. It should not be treated as a direct measure of longer-term drinking behavior. The endpoint’s usefulness for comparing groups depends not only on the group means, but also on the study’s analysis, data completeness, and precision; those additional results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group trial and reports a continuous primary outcome summarized by group means and standard deviations. The posted results contain descriptive statistics, but no inferential analysis for the two-arm comparison. The distinction is important: group summaries describe the observed data, while an inferential analysis estimates uncertainty for a comparison and depends on a specified statistical method.

What does a mean describe?

In general, a mean is a measure of the center of a set of numeric observations. It is calculated from the observations and can be affected by unusually high or low values. The registry reports a mean of 37.57 milliliters in the Endotoxin group and 50.08 milliliters in the Placebo group. These are group summaries for alcohol consumption during the 120-minute session. The record does not provide the participant-level values, so the shape of the distributions and the influence of individual observations cannot be assessed.

What does the standard deviation describe?

In general, a standard deviation describes how much observations vary around their mean. The reported standard deviations are 47.27 milliliters for Endotoxin and 37.58 milliliters for Placebo. A larger standard deviation indicates greater dispersion in the measured values, but does not by itself show whether a group mean is estimated precisely. Precision also depends on the amount of information in the data and the analysis assumptions. The posted group counts are 7.0 and 6.0, and no confidence intervals for the means or comparison are reported.

In general, outcome data with a mean and standard deviation may be analyzed using methods that compare group means, but the appropriate method depends on the distribution, design, and analysis plan. The registry record does not report the planned test, model, covariates, assumptions, or any analysis-specific handling of unusual values. It is therefore not possible to describe the sponsor’s inferential method for the primary endpoint.

Why is there no recalculated comparison?

The registry record indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. It reports each group’s mean, standard deviation, and sample size, but does not post an inferential comparison. A recalculated comparison would require assumptions about the analysis and would not replace an analysis specified and conducted by the trial investigators. The record lists no analysis results, so there is no sponsor analysis to prioritize over such a recalculation. No difference, standard error, test statistic, or confidence interval is calculated in this interpretation.

In general, a confidence interval communicates uncertainty around an estimate under the assumptions of a chosen statistical procedure. It is not a range containing a fixed proportion of individual observations, and it does not establish that an effect is important. No confidence interval is reported for the group means or the contrast between them. The available descriptive summaries therefore support a statement about the observed group means, but not a statement about the precision of the between-group contrast.

What does the planning assumption mean?

The registry includes assumptions for planning illustrations based on the observed effect: a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning description says the effect to detect is a stated fraction of the observed effect. No numerical planning estimates are reported in the registry record. These are planning assumptions, not evidence that the trial had a particular power, and the record does not identify them as the trial’s original design justification.

In general, a sample-size planning illustration estimates how many participants per arm would be required under specified assumptions to detect a target effect with a selected power. Such an illustration depends on assumptions about variability, allocation, the target effect, and the analysis. It should not be described as observed power or as evidence that a completed trial had adequate power. The registry record does not report the trial’s sample-size justification or its planned target enrollment rationale.

The record’s enrollment of 27 and the outcome counts of 7.0 and 6.0 are different quantities in the available report. The record does not describe the participant flow or explain the difference. Without that information, it is not possible to assess how missing outcome data affected the estimates or whether the posted analysis population was defined before outcome data were examined.

In general, randomized assignment supports a comparison of groups when allocation is implemented as planned and the analysis appropriately accounts for the design. Randomization does not ensure that all randomized participants provide outcome data, nor does it determine how missing observations should be handled. The record identifies randomization but does not describe its implementation or the analysis population. These omissions prevent a detailed assessment of the statistical methods beyond the posted descriptive results.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Endotoxin", "Placebo")
n   <- c(7, 6)
m   <- c(37.57, 50.08)
sp  <- c(47.27, 37.58)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Endotoxin  7  37.570  47.270  -6.147  81.287
CARM  Placebo  6  50.080  37.580  10.642  89.518

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no secondary outcomes posted. It also lists zero analyses. Although only one primary outcome is listed, that information alone does not establish what hypotheses or comparisons were prespecified, whether other outcomes were examined, or whether multiplicity was addressed. A multiplicity strategy is not reported in the registry record.

The primary outcome is reported for 7.0 participants in the Endotoxin group and 6.0 in the Placebo group, while overall enrollment is listed as 27. The record does not explain the difference between enrollment and the group counts contributing to the outcome summaries. Participant flow, reasons for unavailable outcomes, and the amount or pattern of missing data are not reported in the registry record.

The record does not report a missing-data method, imputation approach, sensitivity analysis, or complete-case rule. It also does not define the primary analysis population, such as whether the results include all randomized participants or only those with observed session measurements. The population field for the primary outcome is blank. It is therefore not possible to determine how missing outcomes were treated or to assess whether the posted results reflect the originally randomized groups.

In general, missing data can affect a group comparison when the availability of measurements is related to participant characteristics or outcomes. The extent and direction of any such effect depend on why data are missing and on the analysis assumptions. Because the registry record does not describe these details, the influence of unavailable outcomes on the posted means cannot be evaluated. No conclusions about the missingness mechanism or its consequences are supported by the record.

12. 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 0% reporting threshold.

The registry reports serious adverse events for 0 of 7 participants at risk in the Endotoxin group and 0 of 6 participants at risk in the Placebo group. It reports other adverse events for 0 of 7 at risk in the Endotoxin group and 0 of 6 at risk in the Placebo group. Deaths are reported as 0 in each group. These are the safety figures recorded for the groups and participants at risk in the registry.

These counts should be read as the events recorded in the posted safety data, not as proof that no events occurred outside the data collection or reporting process. The registry does not list serious adverse event terms. It also does not provide additional narrative details about how adverse events were collected, coded, or followed over time. The reported safety group counts correspond to the listed at-risk counts; the record does not explain how these groups relate to all 27 enrolled participants.

In general, an event count of zero in a group is an observed count, not a guarantee that the underlying risk is zero. Safety interpretation also depends on the size and follow-up of the group and the completeness of reporting. The registry figures describe what was posted; they do not establish comparative safety or support a broader conclusion about risk.

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

The posted results show that the group mean for alcohol consumed during the 120-minute laboratory session was 37.57 milliliters for Endotoxin and 50.08 milliliters for Placebo. The standard deviations were 47.27 and 37.58, respectively. These summaries describe observed consumption in the reported outcome groups. They do not by themselves establish whether the groups differed reliably or what the size and precision of a group contrast would be.

The registry does not report a statistical comparison, confidence interval, or p-value for the primary endpoint. It also does not report an analysis population or explain why the outcome group counts are smaller than the enrollment figure of 27. Therefore, the descriptive pattern should be interpreted with caution, and the available record does not allow a formal assessment of uncertainty or missing-data effects.

The trial is described as a pilot study in a human laboratory. Its endpoint is consumption during a session, not a measure of long-term drinking behavior. The record gives no basis for extending the observed summaries to settings outside the laboratory, to people not represented in the outcome groups, or to outcomes not reported in the registry.

The results do not establish that endotoxin increases or decreases alcohol consumption. They also do not show that the observed difference is statistically significant, clinically important, or reproducible. Those judgments would require information and analyses not reported in the registry record. The posted means are best understood as preliminary descriptive observations from the reported groups, rather than definitive evidence of an effect.

In general, randomized trials are designed to compare groups under a defined protocol, but the strength of conclusions depends on the implementation, completeness of outcome data, and prespecified analysis. The registry record supplies some design labels and outcome summaries, but important details about participant flow, statistical methods, and uncertainty are not reported. The measured endpoint and the posted safety counts should therefore be kept within the scope of the specific information recorded.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it connects a randomized laboratory intervention with a measured behavioral outcome. The primary endpoint is quantitative and defined over a 120-minute session, allowing the registry to report a group mean and standard deviation for each arm. Those summaries give readers an initial description of the observed data.

The summaries also illustrate why descriptive estimates and inferential conclusions are different. The group means are 37.57 milliliters and 50.08 milliliters, while the standard deviations are 47.27 and 37.58. The data are reported for 7.0 and 6.0 participants. Without a formal comparison or uncertainty interval, the direction of the observed mean pattern does not reveal how precisely the group contrast is estimated. The record’s indication that a two-arm comparison is not estimable makes that limitation particularly visible.

The mismatch between enrollment of 27 and the outcome group counts raises a separate question about which participants contributed data. Statistical interpretation depends on the analysis population and on how incomplete outcomes are handled. Those details are not reported in the registry record, so readers cannot determine whether the posted summaries represent all randomized participants or a subset.

As a pilot study, the record describes an effort to collect preliminary human laboratory data. A pilot outcome can inform understanding of the measurement and provide descriptive observations, but the posted summaries do not establish a definitive treatment effect. The record’s planning assumptions are explicitly presented as illustrations based on the observed effect, rather than as the trial’s own design justification. This distinction helps prevent a planning calculation from being misread as evidence of achieved power.

The study therefore highlights the value of reporting participant flow, analysis populations, inferential estimates, and missing-data methods alongside group summaries. Such information would allow readers to judge how stable and interpretable the observed pattern is, while keeping the conclusions tied to the specific laboratory outcome.

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 limitation of the posted outcome evidence is that it consists of group-level descriptive summaries without an inferential comparison. No confidence interval, p-value, or model-based estimate is reported for the primary endpoint. The registry indicates that a two-arm comparison is not estimable, so the observed means cannot be converted into a reported formal conclusion about the contrast.

The outcome counts are 7.0 in the Endotoxin group and 6.0 in the Placebo group, whereas the recorded enrollment is 27. The registry record does not explain this difference, provide participant flow, or identify the outcome analysis population. Reasons for unavailable outcome data and the methods used to handle them are not reported. These omissions limit assessment of the representativeness of the summaries and the possible influence of missing data.

The record reports means and standard deviations but not participant-level values or distributional information. Consequently, the extent to which observations are skewed or influenced by unusually high or low consumption cannot be assessed. The standard deviations indicate variability, but they do not replace uncertainty estimates for the group comparison.

Further protocol and analysis details are not reported in the registry record. These include the randomization procedure, allocation ratio, masked roles, statistical model, prespecified analysis plan, and sample-size justification. The record also does not report details of endpoint measurement beyond the stated session timeframe and unit. The planned significance level and allocation assumption in the planning description are illustrations and should not be treated as the trial’s design rationale.

Finally, the endpoint is alcohol consumption in a laboratory session. The posted summaries do not provide evidence about longer-term behavior or other outcomes. The study is described as a pilot, and its registry results should be read within that specific context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Endotoxin on Alcohol Consumption — NCT04527185.
• Registry record last updated 2025-11-03; status last verified 2025-07.
• Results first posted 2025-11-03.
• 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 describes NCT04527185, “Effect of Endotoxin on Alcohol Consumption,” as a completed phase 2 randomized, quadruple-masked, parallel-group study sponsored by Yale University. It lists Alcohol Use Disorder as the condition and enrollment of 27. The recorded start date is 2022-02-27 and the primary completion date is 2024-10-31.

The intervention was endotoxin, described as a one-time 0.4ng/kg i.v. administration during the laboratory session; the comparator was placebo. The primary outcome was mean alcohol consumption in milliliters during a 120-minute self-administration session. The posted mean and standard deviation were 37.57 and 47.27 for Endotoxin, based on 7.0 participants, and 50.08 and 37.58 for Placebo, based on 6.0 participants.

No primary comparison or secondary outcome analysis is reported. The registry record does not explain the difference between enrollment and the outcome group counts, or report the analysis population and missing-data methods. Posted safety counts show zero serious adverse events, other adverse events, and deaths in each listed group.