The Effect of NK1R Antagonism on Alcohol Craving and PTSD Symptoms in Alcohol Dependent Patients With PTSD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of NK1R Antagonism on Alcohol Craving and PTSD Symptoms in Alcohol Dependent Patients With PTSD (NCT00896038), a randomized phase 2 study. The primary outcome is Alcohol Craving in Response to the Stress Script.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel phase 2 trial comparing aprepitant with placebo among people with alcohol dependence and PTSD. The registry record lists an enrollment of 58 and a completed status. The recorded study start is 2009-05, and the primary completion is 2014-05. The sponsor was the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

The intervention descriptions specify a 1-week placebo lead-in in both groups. After that lead-in, the aprepitant group received 125 mg orally daily for 21 days, while the comparator group continued oral placebo daily for 21 days. The registry record does not report the method used to generate the randomization sequence, allocation concealment, or the identities of those included in the triple masking.

The brief summary describes an intended population of 120 participants, with stratification by PTSD etiology and balancing for sex within strata. However, enrollment is recorded as 58. The registry record does not establish whether the proposed stratification and balancing procedures were implemented as planned, nor does it give a reason for the difference between intended recruitment and recorded enrollment.

The primary outcome is a continuous craving score assessed in relation to a stress-script procedure. The primary outcome population was restricted to participants completing all three script types. The registry record reports 26 aprepitant participants and 24 placebo participants for this outcome. Those outcome counts differ from the adverse-event risk populations, which were 30 and 28, respectively; the record does not explain the difference. Detailed eligibility criteria, follow-up beyond the stated treatment and outcome timing, and a complete protocol 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analyses included only those subjects who completed all three script types (neutral, alcohol, stress)

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 Craving in Response to the Stress Script, measured over 15 minutes prior to the beginning of stress script presentation, which occurred on Day 25, 26, or 27 of the treatment period.

The primary endpoint was alcohol craving in response to the stress script, measured with the Alcohol Urges Questionnaire (AUQ). The instrument is described as an 8-item self-administered measure of craving in the current context, meaning craving “right now.” Its possible score ranges from 8, the lowest craving value, to 56, the highest craving value. The reported outcome is a mean, so the group results describe average scores rather than the distribution of individual participants’ scores.

The measurement was taken 15 minutes before stress-script presentation, which occurred on Day 25, 26, or 27 of the treatment period. This timing means the reported score is a pre-script assessment associated with the stress-script visit; it is not described as a change from before to after the script. The registry record does not report a post-script primary score or a change-score analysis.

Craving is relevant to the trial’s stated question because its brief summary connects stress and negative affective states with relapse risk and describes interest in a candidate target related to stress responses. That rationale is background, not evidence that the measured endpoint predicts an individual participant’s future drinking or relapse. The registry record does not report such a validation analysis. The primary outcome analysis included only participants who completed the neutral, alcohol, and stress scripts, so its reported group means apply to that defined analysis population rather than necessarily to everyone enrolled.

7. Results Posted in the Registry

• Aprepitant: mean 11.90 versus 12.90 on control; difference -1.00 (95% CI -7.49 to 5.49), standardized effect d = -0.09; z-test p = 0.763.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: each participant has an AUQ score, and the primary group summaries are means. A mean difference expresses the contrast between the two group means in the original score units. In this trial, the reported contrast is aprepitant minus placebo, so a negative value indicates a lower observed average in the aprepitant group. The estimate of -1.0 is the observed difference between means, not a comparison of individual trajectories or a measure of within-person change.

The reported standard errors are 2.29 for aprepitant and 2.39 for placebo. General explanation: a standard error describes the estimated sampling variability of a statistic, such as a group mean. It is not the spread of individual scores. The registry record identifies the arm-level dispersion as standard error; it does not report standard deviations for the primary endpoint. The pooled standard deviation used in the simple recalculation is 11.69, but the posted trial result does not provide a sponsor analysis or adjusted estimate alongside it.

The comparison includes a confidence interval from -7.488 to 5.488 and an unadjusted p-value of 0.763. General explanation: a confidence interval represents a range of values compatible with the estimate under the method’s assumptions, and its width conveys precision. A p-value assesses how compatible the observed data are with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true. The record labels the p-value unadjusted, so it should not be read as accounting for testing multiple outcomes or contrasts.

The effect-size summary is d = -0.086. General explanation: a standardized mean difference expresses a mean contrast relative to a measure of score variability, allowing scale-free comparison in some settings. It is not expressed in AUQ units and does not replace the original-scale mean difference or its confidence interval. The record does not report a prespecified threshold for interpreting the standardized effect.

General explanation: assumptions behind a simple two-group mean comparison can include independent observations, an appropriate model for the outcome, and a suitable treatment of variability. The registry record does not report enough detail to determine the exact primary analysis model, whether covariates were used, whether site or stratification factors were included, or whether model diagnostics were assessed. The simple recalculated contrast is unadjusted from posted summary statistics; it is not a substitute for a trial’s own prespecified analysis. The registry record does not post an analysis plan or a sponsor-generated adjusted estimate for comparison.

The outcome population requires particular attention. Only participants completing all three script types were included in the primary analyses. General explanation: restricting analysis to completers can affect interpretation if completion is related to treatment assignment, outcome values, or participant characteristics. The registry record does not describe the amount or pattern of missingness, reasons for noncompletion, or any imputation or sensitivity analyses. It is therefore not possible to assess from the record whether the completer restriction could have altered the estimated contrast.

The trial is described as randomized, triple-masked, and parallel. General explanation: randomization is intended to make treatment groups comparable on average at allocation, masking is intended to reduce certain sources of bias, and a parallel design assigns participants to a group followed through the study rather than having each participant receive both treatments. These design labels do not by themselves establish how allocation was generated, how masking was maintained, or whether masking was successful; those operational details are not reported in the registry record.

The trial record lists 17 outcome measures and no posted secondary results. General explanation: when many outcomes, time points, or contrasts are tested, the chance of at least one nominally unusual result can increase. Methods to address multiplicity may include prespecifying a primary outcome, adjusting significance thresholds, or treating other analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or interim analyses. The primary p-value is explicitly unadjusted, and no further adjustment should be inferred.

The enrollment recorded is 58, while the brief summary describes an intended sample of 120. General explanation: sample-size planning depends on assumptions about the target effect, outcome variability, significance level, power, and design. The trial’s own original assumptions and justification are not reported in the registry record. The separate planning illustration is based on the observed effect and is not evidence of the trial’s original plan or its achieved power.

10. Confidence Intervals and Precision

The estimated mean difference is -1.0 AUQ units, with a confidence interval from -7.488 to 5.488. This interval is wide in relation to the point estimate and crosses zero. It therefore reflects uncertainty about both the direction and size of the group contrast. The data are compatible with a lower mean in the aprepitant group, little or no mean difference, or a higher mean, within the bounds of the interval and its statistical assumptions.

General explanation: a confidence interval is not a range containing a fixed proportion of individual participants’ scores. It describes uncertainty in an estimated population contrast. A narrower interval would indicate greater precision, while a wider interval leaves more possible values compatible with the data. The interval does not, by itself, identify which values are clinically important. No clinically important difference threshold is reported in the registry record.

The arm-level standard errors are 2.29 and 2.39, and the primary analysis includes 26 aprepitant participants and 24 placebo participants. These values help contextualize the precision of the group means, but they do not reveal the full score distribution or explain why the endpoint analysis population was smaller than the adverse-event populations. Missing-data patterns and reasons for exclusion are not reported in the registry record.

The unadjusted p-value of 0.763 is consistent with substantial uncertainty about the contrast under the test’s assumptions. It should not be interpreted as a probability that the treatments are identical. Nor does the confidence interval demonstrate equivalence: an equivalence conclusion would require a prespecified equivalence margin and an analysis designed for that purpose, neither of which is reported in the registry record. The result is best read as an imprecise estimate of a mean difference for this particular endpoint and analysis population.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, rather than the trial’s original design assumptions, which are not reported in the registry record. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect.

The rows describe planning for 100%, 75%, and 50% of the observed effect. For each assumed effect, the 80% power column gives the estimated number of participants per arm under which the design would have an 80% chance of detecting that effect at the stated significance level, if the assumptions hold. The 90% power column gives the corresponding estimate for a 90% chance. These are planning quantities, not counts of participants who actually took part.

The figures increase as the assumed effect becomes smaller: detecting a smaller contrast generally requires more participants, all else being equal. The listed values should be treated as illustrative rather than as a recommendation or a reconstruction of the trial’s own planning. This is not observed power; it does not describe the probability that the completed trial detected an effect, and it should not be used to explain the trial’s result after the fact.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.000; pooled standard deviation σ = 11.692.
2. n = 2 × (1.96 + 0.842)² × 11.692² / -1.000² = 2,145.9, rounded up to 2,146 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1                      # observed difference in means
sigma <- 11.6920059941255                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(896038)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,146 (80% power), 2,873 (90% power)
 75% of observed effect: n per arm = 3,815 (80% power), 5,108 (90% power)
 50% of observed effect: n per arm = 8,584 (80% power), 11,492 (90% power)
power.t.test: 2146.9 
Simulated power at n = 2,146 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 17 outcome measures, while the posted results include the primary outcome and no posted secondary results. It does not report a statistical analysis plan specifying the hierarchy among outcomes, planned contrasts, or time points. The p-value for the primary comparison is unadjusted. No multiplicity adjustment or rationale for not adjusting is reported in the registry record.

General explanation: multiplicity becomes relevant when several outcomes or comparisons are examined, because repeated testing can increase the chance of finding at least one result that appears unusual by chance. Prespecifying a primary outcome and distinguishing confirmatory from exploratory analyses can help readers understand the intended evidential role of each test. The registry record identifies a primary endpoint but does not provide enough information to determine how other planned analyses were handled.

The primary outcome analysis included participants who completed all three script types. The registry record does not report the number or characteristics of participants who did not complete the required scripts, reasons for noncompletion, or whether missing measurements were imputed. It also does not describe sensitivity analyses assessing whether the completer-only result depends on assumptions about missing data.

The outcome analysis counts are 26 for aprepitant and 24 for placebo, whereas the adverse-event risk groups include 30 and 28. The record does not explain the difference between these populations. It does not report an intention-to-treat analysis, a per-protocol definition, or how participants were handled after randomization if they did not complete the scripts. These omissions limit assessment of the analysis population and of possible selection associated with completion.

Interim analyses, stopping rules, and the trial’s full statistical analysis plan are not reported in the registry record. Their absence from the record should not be taken as evidence that they were or were not used; their status cannot be determined from the posted information.

14. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

For serious adverse events, the reported affected counts are 0 among 30 participants at risk in the aprepitant group and 0 among 28 participants at risk in the placebo group. These are counts of participants affected, not a measure of the duration or severity of non-serious events. The registry record lists no serious adverse-event terms.

For other adverse events, the reported affected counts are 30 among 30 participants at risk in the aprepitant group and 25 among 28 participants at risk in the placebo group. These figures describe participants recorded as affected in each risk group; they do not provide event counts per participant, event duration, or a comparison adjusted for differences in exposure. The registry record does not provide further detail about the other adverse events in this record.

Death counts are not reported in the registry record. The absence of reported serious adverse events should be read as a feature of the posted registry data, not as proof that no adverse experiences of any kind occurred. The adverse-event population also differs from the primary outcome population, and the record does not explain that difference.

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

The posted primary results describe average AUQ scores before the stress-script presentation among participants who completed all three script types. The mean was 11.9 in the aprepitant group and 12.9 in the placebo group, with an estimated mean difference of -1.0. The confidence interval, from -7.488 to 5.488, indicates substantial uncertainty about the size and direction of the population contrast. The unadjusted p-value was 0.763.

These results do not establish that the groups were equivalent, that there was no effect, or that any possible difference is clinically unimportant. The registry record does not state a clinically important AUQ threshold or an equivalence margin. The result also does not show whether craving changed after exposure to the stress script, because the primary measurement is described as occurring before script presentation.

The endpoint is alcohol craving in the current context, measured at a specified study visit. It is not a direct report of alcohol consumption, relapse, or PTSD symptom change. Although the trial’s brief summary discusses PTSD symptoms and the rationale for studying stress-related responses, the posted primary result does not establish an effect on those outcomes. No secondary results are posted in the registry record.

Interpretation is limited to the recorded analysis population and the statistical information available. The primary analysis included fewer participants than the overall enrollment, and the registry record does not explain the difference between the primary outcome and safety populations or describe missing-data handling. The observed means and interval should therefore be understood as an estimate for the reported completer analysis, not as a complete account of every randomized participant’s outcomes.

The planning illustrations cannot resolve these interpretive limits. They are based on the observed effect under stated assumptions and are not the trial’s original sample-size justification or a measure of achieved power. Overall, the registry record supports a description of an uncertain mean contrast on one primary craving measure, without a basis for broader conclusions about clinical outcomes.

16. Why This Trial Matters Statistically

This trial illustrates why an estimated effect and its precision should be considered together. The mean difference is -1.0 AUQ units, but its confidence interval spans values on both sides of zero and extends from -7.488 to 5.488. The point estimate alone would conceal how uncertain the comparison remains.

It also illustrates the importance of defining an outcome precisely. The primary endpoint is a current-context craving score measured before the stress script, rather than a post-script change or a behavioral outcome. The timing and analysis population determine what question the estimate answers. The primary result pertains to participants who completed all three script types, while the record does not explain why the endpoint and safety populations differ.

Trial labels such as randomized, triple-masked, and parallel describe important design features, but they do not supply all the information needed to assess analysis choices. The registry record does not report the detailed randomization procedures, the complete statistical plan, missing-data methods, or multiplicity strategy. Those details matter when judging how the reported estimate was produced and what uncertainty remains.

Finally, the contrast between intended recruitment in the brief summary and recorded enrollment makes it especially important not to infer the original planning rationale from a retrospective illustration. Sample-size figures based on the observed effect answer a planning question under explicit assumptions; they do not tell readers whether the original trial was adequately planned or how likely it was to detect a different effect. Clear separation of observed results, uncertainty, and planning assumptions is central to responsible interpretation.

17. 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 has several limits relevant to this trial. The brief summary describes intended recruitment of 120 participants, while recorded enrollment is 58. The record does not explain the difference or report the trial’s original sample-size justification. Although the summary describes stratification by PTSD etiology and balancing by sex, the registry record does not confirm whether these procedures were implemented.

The primary outcome analysis was restricted to participants completing all three script types. The record does not report reasons for noncompletion, characteristics of excluded participants, or missing-data methods. The primary endpoint counts are 26 and 24, whereas the safety risk groups are 30 and 28; the relationship between these populations is not explained.

The primary score was measured 15 minutes before stress-script presentation on Day 25, 26, or 27. The registry record does not report a primary post-script score or a change analysis. It also does not provide a clinically important difference threshold, a detailed statistical analysis plan, the full primary model, or information on adjustment for covariates or stratification.

The registry lists 17 outcome measures but posts no secondary results, and the primary p-value is unadjusted. A multiplicity strategy, interim analyses, stopping rules, and detailed handling of missing data are not reported in the registry record. Death counts are also not reported. These limitations constrain interpretation to the posted primary mean contrast and adverse-event counts, rather than supporting broader conclusions about all trial outcomes.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: The Effect of NK1R Antagonism on Alcohol Craving and PTSD Symptoms in Alcohol Dependent Patients With PTSD — NCT00896038.
• Registry record last updated 2015-11-03; status last verified 2015-10.
• Results first posted 2015-11-03.
• 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.

21. Record Summary

The registry record describes a completed, randomized, triple-masked, parallel phase 2 trial sponsored by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Recorded enrollment was 58. The study compared aprepitant, given orally at 125 mg daily for 21 days after a 1-week placebo lead-in, with placebo given during the lead-in and daily for 21 days.

The primary outcome was AUQ alcohol craving measured before stress-script presentation. The reported means were 11.9 for aprepitant and 12.9 for placebo; the mean difference was -1.0, with a confidence interval from -7.488 to 5.488 and an unadjusted p-value of 0.763. The analysis included participants completing all three script types.

The record reports no serious adverse events among the listed risk groups, and other adverse events affected 30 of 30 aprepitant participants and 25 of 28 placebo participants. Secondary results, detailed analysis methods, missing-data handling, and the trial’s original sample-size assumptions are not reported in the registry record.