Effect of Oxytocin on Stress Response in Cocaine-dependent Individuals: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Oxytocin on Stress Response in Cocaine-dependent Individuals (NCT01963091), a randomized phase 2 study. The primary outcome is Salivary Cortisol Levels.

2. Clinical Question

The clinical question concerns a short-term response in a laboratory stress setting. The registry background describes stress as associated with craving and relapse in substance-dependent individuals, and presents oxytocin as a candidate for study because of prior laboratory findings about stress responses. Those statements explain the rationale; they are not findings from this trial. The trial results address measurements taken immediately after the specified task, rather than longer-term stress, craving, relapse, withdrawal, or treatment outcomes.

The comparison is between assigned groups, not between participants’ measurements before and after treatment. The registry record does not report baseline cortisol values or a change-from-baseline analysis. It also does not report outcomes beyond the post-task measurements listed. Consequently, the primary question is narrow: how the two groups’ recorded salivary cortisol means compare at the specified assessment. The secondary ratings add information about participants’ reported stress and craving, but they do not replace the primary physiological measure.

3. Trial Design

The registry describes a randomized, double-masked, parallel Phase 2 trial with an enrollment of 33. Participants were assigned to an oxytocin group or a placebo group. The posted primary results include 17 participants in the oxytocin group and 16 in the placebo group. The registry lists saline as an intervention and labels the comparator group Placebo, but does not describe the masking procedures, allocation concealment, or how treatment assignment was implemented.

The study is marked completed. Its recorded start is 2011-07, and its primary completion is 2012-10. The sponsor is Medical University of South Carolina. The registry title identifies the study as an examination of oxytocin and stress response in cocaine-dependent individuals. The brief description calls it a pilot protocol intended to provide preliminary data. That description supports a cautious reading of the results as exploratory; the registry does not give the original sample-size justification or explain how enrollment was selected.

The primary outcome is salivary cortisol, reported as a mean with standard deviation, measured at 0 minutes post 15 minute stress task. Two secondary outcomes are also posted: Likert scale ratings of subjective stress and subjective craving at the post-task assessment. The registry record does not report detailed dosing, the exact study visit schedule, other measurement procedures, or analysis populations. Nor does it list sponsor-reported statistical analyses. These omissions limit what can be said about implementation and the original analysis plan, even though the group-level outcome summaries are available.

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

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 Salivary Cortisol Levels, measured over 0 minutes post 15 minute stress task.

The primary endpoint is salivary cortisol, measured at 0 minutes after a 15 minute stress task and reported in mg/dl. The registry presents the outcome as a mean and standard deviation for each group. Cortisol is a physiological measure relevant to the stated study question because the protocol concerns the body’s response to stress. The registry description says that hormones released from the brain may mediate behavioral responses to stress; it does not provide additional details about cortisol measurement or its interpretation.

The assessment is a single post-task time point. It therefore describes cortisol at that moment, not the full course of a response during or after the task. The registry record does not report a pre-task cortisol measure, a change score, repeated measurements, or a separate measure of recovery. The results should be read as a between-group comparison at the stated time, not as evidence about how cortisol changed within individuals.

Using a physiological endpoint alongside subjective stress and craving ratings allows the study to describe different kinds of responses to the same task. These measures need not move together: a laboratory measure and a self-reported rating capture distinct aspects of the assessment. The primary endpoint remains cortisol, while the Likert ratings are secondary outcomes. The registry record does not report a clinical threshold for cortisol or define a difference that would be considered important.

7. Results Posted in the Registry

• Oxytocin: mean 0.18 versus 0.22 on control; difference -0.04 (95% CI -0.10 to 0.02), standardized effect d = -0.44; z-test p = 0.202.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Likert Scale Rating of Subjective Stress

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Oxytocin: mean 4.18 versus 4.25 on control; difference -0.07 (95% CI -2.26 to 2.12), standardized effect d = -0.02; z-test p = 0.950.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oxytocin and the control. The interval gives the range of effects that remain compatible with the data.

Likert Scale Rating of Subjective Craving

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Oxytocin: mean 3.35 versus 3.13 on control; difference 0.22 (95% CI -2.14 to 2.58), standardized effect d = 0.06; z-test p = 0.855.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Oxytocin and the control. The interval gives the range of effects that remain compatible with the data.

The subjective stress and craving outcomes follow a broadly similar inferential pattern to the primary cortisol result: the posted group comparisons do not establish a clear separation, and their uncertainty intervals include zero. The point estimates do not all point in the same direction. This means the secondary measures do not form a consistent pattern that would make the primary result more conclusive.

These outcomes relate to the primary question because they capture participants’ reported experience after the same stress task, whereas salivary cortisol is a physiological measure. Agreement across distinct measures could be informative, and disagreement could also be scientifically relevant. In this record, however, the summaries do not support a firm account of how subjective and physiological responses relate. The registry does not report participant-level associations between cortisol and either rating, so it is not possible to assess whether individuals with higher cortisol also reported more stress or craving.

The secondary outcomes are not substitutes for the primary endpoint. They measure different constructs, are recorded on Likert scales, and are reported at the post-task assessment. The registry record does not provide scale ranges, a threshold for meaningful change, or evidence about the measurement properties of these ratings in this study. Their interpretation is therefore limited to the posted group summaries and comparisons.

Unadjusted secondary results carry less weight when several outcomes are examined without a reported plan for multiplicity. In general, testing multiple outcomes can increase the chance that at least one result appears notable by chance. That general concern does not establish that any particular result is spurious. It does mean the secondary comparisons should be viewed as exploratory, especially since the registry lists no reported analyses and does not describe a prespecified hierarchy or adjustment procedure. The overall pattern can inform hypotheses for later research, but it does not independently confirm a treatment effect or resolve the uncertainty around the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Likert Scale Rating of Subjective Stress
• Likert Scale Rating of Subjective Craving

9. Statistical Interpretation

10. Statistical Methods Explained

Each continuous outcome is summarized by a group mean and standard deviation. A mean describes the group’s average measurement; the standard deviation describes how spread out individual measurements are around that average. These summaries provide useful context for the size of the observed group difference, but they do not show the distribution of individual values or whether any observations were unusual.

What does the mean difference represent?

The posted comparison is the mean in the oxytocin group minus the mean in the placebo group. A negative estimate therefore indicates a lower observed mean in the oxytocin group; a positive estimate indicates a higher one. For the primary outcome, that estimate is -0.04 mg/dl. The estimate is an absolute difference on the outcome’s measurement scale, not a percentage change. The registry record does not report an adjusted comparison or a model incorporating participant characteristics.

The comparison figures are unadjusted recalculations from the posted summary statistics. The registry record lists no reported analyses. This distinction matters: a recalculation based on group means and standard deviations is not evidence that the study sponsor prespecified or performed that exact inferential analysis. The record does not describe the original statistical method, any covariate adjustment, or the analysis plan. The registry record reports no discrepancy between the posted summary and the recalculated comparison.

How should a confidence interval be understood?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to calculate it. A narrower interval indicates greater precision; a wider interval indicates less precision. For a difference, an interval that includes zero is compatible with no difference as well as with differences in either direction, within the interval’s limits. The primary interval includes zero, so the estimate does not distinguish clearly between a lower mean, no difference, or a higher mean in the oxytocin group. This interpretation does not mean that every value in the interval is equally plausible or that the interval assigns a probability to the true effect.

The confidence intervals and p-values are unadjusted. In general, a p-value assesses how unusual results at least as incompatible with a specified null value would be under a statistical model. It is not a direct measure of clinical importance and does not give the probability that the null hypothesis is true. Here, the primary unadjusted p-value is 0.202. Its meaning depends on the statistical assumptions behind the calculation, and the registry record does not report the sponsor’s test or model.

Why does variation matter?

In general, greater variability among participants makes a group mean harder to estimate precisely when sample size is held fixed. Standard deviations describe observed spread, while standard errors describe uncertainty in an estimated mean. They are different quantities and should not be interchanged. The registry reports standard deviations for the outcome summaries; the displayed recalculations use the posted group summaries to estimate differences and uncertainty. The participant counts are modest, so the observed means can be sensitive to the particular participants enrolled. The registry record does not report distributional checks or diagnostics.

Over-dispersion is a general concern when observed variability is larger than a statistical model assumes. If a model understates variability, its uncertainty estimates may be too small and its intervals too narrow. That concern is not evidence that over-dispersion occurred in this trial. The registry record does not report a model-based analysis or diagnostic information sufficient to assess it. For the Likert outcomes, the posted summaries are means and standard deviations, but the record does not describe the scale’s range or the distribution of responses. Interpretation should therefore remain tied to the reported summaries.

What do the planning illustrations mean?

In general, power is the probability that a specified analysis will detect an effect of a chosen size under stated assumptions. The planning illustrations use the observed effect as a reference and show hypothetical participant counts for detecting the stated fractions of that effect. They are not a reconstruction of the trial’s original design process. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations report participants per arm for these continuous outcomes. They are planning calculations, not observed power, and they do not indicate the probability that the observed result is true.

Power and precision are related but not interchangeable. Planning for a smaller target effect generally requires more participants to distinguish that effect from random variation under otherwise fixed assumptions. The effect used in a planning illustration is an assumption, not a guaranteed future result. Since the observed effect in a small pilot may itself be uncertain, using it as the basis for a later study’s planning requires judgment beyond the calculations shown. The registry record does not report its original design assumptions or sample-size justification.

11. Confidence Intervals and Precision

The primary mean difference is -0.04 mg/dl, with a confidence interval that runs from -0.101 to 0.021 in the posted recalculation. This interval crosses zero. It therefore does not isolate a single direction of difference: the estimate remains compatible with values on either side of no difference under the calculation’s assumptions. The interval is broad relative to the point estimate, illustrating the limited precision of the comparison.

Precision depends on both the spread of the measurements and the number of participants contributing data. The primary group summaries include 17 participants assigned to oxytocin and 16 assigned to placebo. These counts and the reported standard deviations help explain why the estimated difference remains uncertain. A confidence interval is not a guarantee that the true effect lies within its limits, and it is not a range of individual participant responses. It describes uncertainty in the estimated group difference.

The secondary intervals are also wide enough to include zero. Their uncertainty reinforces the need to avoid interpreting small differences in the point estimates as reliable separations between groups. A narrow estimate around zero would support a different precision judgment than a wide estimate that includes effects in either direction; the posted results are not precise enough to make a strong claim of equivalence.

In general, more information can improve precision, but a larger study would not guarantee a particular result. Its value would depend on the outcome variability, the effect it is designed to detect, the analysis plan, and the completeness and quality of outcome data. The registry record does not report a clinically important difference against which to judge whether the intervals exclude effects that matter. Precision is therefore statistical, not a determination of clinical importance.

12. 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 refer to participants per arm for these continuous outcomes, not total events. They are based on a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each row, the target effect is the stated fraction of the observed effect: the full observed effect, 75% of the observed effect, or 50% of the observed effect. The original trial’s design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the hypothetical participants per arm needed, under those assumptions, for an analysis to have an 80% chance of detecting the specified target effect. The 90% power column gives the corresponding planning count for a 90% chance. These are conditional planning quantities: they depend on the assumed effect and the calculation’s other assumptions. They are not forecasts of the results of a future study.

Smaller effects are harder to distinguish from random variation, so the planning illustrations require more participants when the assumed target is a smaller fraction of the observed effect. This is why the required counts rise across the rows with smaller target effects. The displayed counts are illustrations based on observed estimates, which may be unstable in a pilot study. They should not be read as a recommendation without considering the scientific question, outcome variability, and design details. These figures are not observed power.

13. 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 = -0.040; pooled standard deviation σ = 0.090.
2. n = 2 × (1.96 + 0.842)² × 0.090² / -0.040² = 79.5, rounded up to 80 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 <- -0.04                      # observed difference in means
sigma <- 0.09                     # 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(1963091)
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 = 80 (80% power), 107 (90% power)
 75% of observed effect: n per arm = 142 (80% power), 190 (90% power)
 50% of observed effect: n per arm = 318 (80% power), 426 (90% power)
power.t.test: 80.4 
Simulated power at n = 80 per arm: 0.795 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes. It does not report a multiplicity strategy, such as a hierarchy among outcomes or a correction for multiple comparisons. This absence matters because examining several outcomes can increase the chance of at least one apparently unusual result even when there is no true effect. In general, a prespecified strategy helps define how evidence across outcomes should be interpreted. Without one reported, the secondary comparisons are best treated as exploratory, and their unadjusted p-values should not be read as if they were the only tests considered.

The record lists no sponsor-reported analyses. It therefore does not specify the original model, handling of covariates, analysis population, missing-data approach, or whether any analyses were planned at interim time points. These matters are not reported in the registry record. Their absence does not show that no such procedures existed; it means the posted record does not allow them to be evaluated.

The outcome summaries include group counts, but the registry does not explain how those counts relate to all randomized participants or whether any outcome data were missing. It does not describe an intention-to-treat population, a per-protocol population, exclusions, or imputation. The record therefore does not establish whether all randomized participants were included in each outcome analysis or how incomplete measurements were handled. Missingness can affect estimates if the participants with observed outcomes differ from those without them; this is a general concern, not a claim that missing data occurred.

The registry reports randomized, double-masked, parallel allocation, but does not describe the masking process, allocation concealment, deviations from assigned treatment, or adherence. It also does not provide details of any interim monitoring. These omissions limit appraisal of the conduct and analysis without changing the numerical results that are posted. A complete interpretation would require a prespecified protocol and fuller analysis reporting, neither of which is described in the registry record.

15. 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.

The registry reports zero serious adverse events among the 17 participants at risk in the oxytocin group and among the 16 participants at risk in the placebo group. It also reports zero other adverse events in the corresponding at-risk groups. These figures describe what was reported for the groups in this record; they do not establish that no events of any kind occurred outside the categories or reporting period captured by the registry.

Deaths are not reported in the registry record. The record does not provide event definitions, collection procedures, follow-up duration for safety, or details about whether events were assessed as related to treatment. With a small trial and limited safety information, the absence of reported events cannot rule out uncommon harms or characterize safety beyond the observed participants and the registry’s reporting. These figures should be read as a summary of reported events, not as a comprehensive safety assessment.

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

The result shows a modest observed difference in mean post-task salivary cortisol between the groups, with the oxytocin group’s mean lower than the placebo group’s mean. The unadjusted estimate is -0.04 mg/dl, but its confidence interval includes zero and its unadjusted p-value is 0.202. The evidence is therefore not precise enough to establish a clear difference in this trial. Equally, the findings do not prove that the treatments have identical effects.

A result that is not statistically clear can arise when the true difference is small, when measurements are variable, when the sample is limited, or through combinations of these factors. The posted summaries cannot distinguish among those possibilities. The confidence interval communicates uncertainty about the group contrast; it does not describe the range of responses among individuals, and it does not indicate the probability that either treatment is effective.

The evidence is bounded by the study’s setting and outcomes. The measurements concern salivary cortisol and subjective ratings immediately after a 15 minute stress task in participants with cocaine dependence. The results do not establish effects on craving outside that assessment, drug use, relapse, withdrawal, or longer-term outcomes. The registry’s scientific rationale discusses possible relationships between stress and relapse, but those broader outcomes are not reported in the posted results.

The trial is described as a pilot and enrolled 33 participants. Its results can be useful as preliminary estimates and as a basis for refining questions for further research, but they leave substantial uncertainty. The registry does not report a clinically important difference, the original sample-size justification, or a full statistical plan. No conclusion about medical benefit, lack of benefit, or suitability for an individual follows from these data.

17. Why This Trial Matters Statistically

This trial illustrates why the direction of a point estimate is not enough to establish a group difference. The oxytocin group had a lower observed cortisol mean, but the confidence interval extends across zero. Reading both the estimate and its uncertainty avoids turning a small pilot result into a categorical claim. It also makes clear that a non-significant comparison is not the same as evidence of equivalence.

The study also shows the value of distinguishing measurement types. Cortisol is a physiological endpoint, while subjective stress and craving ratings reflect self-reported experience. Considering both may help frame a research question, but their results cannot be treated as interchangeable or combined informally. In this trial, the secondary comparisons do not resolve the uncertainty in the primary result, and the registry does not report whether outcomes were evaluated under a multiplicity plan.

Planning illustrations based on observed effects are another useful statistical lesson. They show how assumed effect size influences required participant counts, while also making the uncertainty of a pilot estimate important. Such figures can support discussion of future study design, but they are not evidence that a study had a particular probability of detecting an effect after results are known. The original design assumptions are not reported.

Finally, the registry record demonstrates the limits of interpreting summary results without an analysis plan and fuller reporting. Allocation and outcome summaries are available, but details about missing data, analysis populations, statistical models, and safety follow-up are not. Recognizing both what the record documents and what it leaves unknown is central to sound statistical interpretation.

18. 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 enrollment was 33, and the study is described as a pilot. The resulting group summaries and comparisons are imprecise, particularly for conclusions about effects that may be smaller than the observed point estimate. The planning illustrations are based on observed effects and should not be taken as a substitute for a design justified independently of these results.

The primary endpoint is measured at a single post-task time point. Without a reported baseline measure or repeated measurements, the results do not describe within-person change, the timing of a response, or recovery after the stress task. The registry record does not report further details of the task, the cortisol collection procedure, or the measurement schedule. These gaps restrict interpretation of what the single measurement represents.

Other important design and analysis details are not reported in the registry record. These include eligibility criteria beyond the listed condition, intervention dose and administration schedule, allocation concealment, adherence, the analysis population, missing-data handling, model specification, and a multiplicity plan. The registry record also does not state a clinically important difference for cortisol or the Likert outcomes. Consequently, statistical uncertainty cannot be translated into a judgment about clinical importance.

The results are specific to the participants and laboratory assessment in this trial. The registry record does not report longer-term clinical outcomes such as relapse or ongoing substance use. Safety summaries record no serious or other adverse events in the reported at-risk groups, but deaths and further safety details are not reported in the registry record. These limitations do not negate the posted results; they define the boundaries of the conclusions they can support.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect of Oxytocin on Stress Response in Cocaine-dependent Individuals — NCT01963091.
• Registry record last updated 2018-06-04; status last verified 2018-05.
• Results first posted 2014-02-05.
• 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.

22. Record Summary

The registry describes a completed randomized, double-masked, parallel Phase 2 trial sponsored by Medical University of South Carolina, with an enrollment of 33. The study compared oxytocin with placebo in individuals with cocaine dependence. The primary outcome was mean salivary cortisol at 0 minutes post 15 minute stress task; subjective stress and craving ratings were listed as secondary outcomes.

The primary unadjusted recalculated mean difference was -0.04 mg/dl, with a confidence interval that includes zero and an unadjusted p-value of 0.202. The secondary comparisons likewise do not establish clear group differences. The registry record lists no sponsor-reported analyses and does not report the original sample-size justification, multiplicity strategy, or missing-data approach. The results are preliminary, imprecise comparisons of post-task measures, not evidence about longer-term clinical outcomes.