Oxytocin and Affect Processing in Posttraumatic Stress Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oxytocin and Affect Processing in Posttraumatic Stress Disorder (NCT02546570), a randomized phase 2 study. The primary outcome is fMRI Analysis: Change in Anterior Insula Region.

2. Clinical Question

The study description concerns oxytocin’s influence on affective processing across trauma-exposed and non-trauma-exposed adults, including participants with and without PTSD. Gentle forearm brushing was intended to engage C-tactile nerves and social-emotional processing; palm brushing served as a control because C-tactile afferents do not innervate the palm. The stated comparison therefore involves both the drug condition and the type of brushing stimulus, rather than a simple comparison of diagnostic groups alone.

The registry lists healthy controls, adults with PTSD, and trauma-exposed adults without PTSD. However, the outcome description says that data for all enrolled participants are summarized, and the registry record does not provide separate primary-outcome estimates by group. It also does not report a numerical estimate of the oxytocin-versus-placebo effect. Consequently, the stated research question can be described, but the direction, size, and precision of the primary result cannot be assessed from the posted record.

3. Trial Design

This is a phase 2, randomized, double-masked trial with a parallel model recorded in the registry. The listed interventions are oxytocin and placebo. Enrollment was 11, and the study status is completed. The registry lists PTSD as a condition and describes three adult groups: healthy controls, adults with PTSD, and trauma-exposed adults without PTSD.

There is an important design-description ambiguity. Although the registered model is parallel, the arm descriptions say that each group received both oxytocin and placebo nasal spray in a within-subjects design, with the order blinded and counterbalanced across two laboratory sessions. Those descriptions also specify a dose of 24 IU. A within-subject comparison means that a participant’s observations under one condition can be compared with that same participant’s observations under the other condition; a parallel comparison instead assigns different participants to different conditions. The registry record does not explain how these descriptions relate or which design governed the primary analysis.

The primary measure is described in connection with fMRI data collected at the second and third visits, one week apart. The trial description also mentions behavioral measures, neuroimaging, and peripheral hormone measurements. Salivary oxytocin is listed as a secondary outcome, and the record lists 8 outcome measures overall. These details identify the broad measurement plan, but do not establish which outcomes were analyzed, how they were modeled, or whether all planned visits and measurements were completed.

The record does not report a sample-size justification, a detailed allocation procedure, the method used to maintain masking, or a statistical analysis plan. It also does not explain the relationship between the registered parallel model and the within-subject descriptions. These omissions limit the ability to reconstruct the design and intended analysis from the registry alone. The enrollment count is small, but the registry provides no stated target or justification against which to assess whether that count met the study’s design goals.

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: Data for all enrolled are summarized.

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.

Population: Combat Veterans

6. Primary Endpoint

The registry lists the primary outcome as fMRI Analysis: Change in Anterior Insula Region, measured over 1 week; fMRI data collected at second and third visits, one week apart.

The primary endpoint is titled “fMRI Analysis: Change in Anterior Insula Region.” It is described as a mean, with the unit given as percentage of area activation and dispersion specified as a 95% confidence interval. The broader endpoint description concerns change in blood-oxygen-level dependent (BOLD) contrast signal in regions relevant to fear/threat and reward processing. Examples named in the record include the amygdala and ventral striatum, alongside the anterior insula named in the endpoint title.

The task contrasted BOLD responses during gentle continuous brushing of the forearm and the palm. The rationale in the record is that forearm brushing targets C-tactile nerves, which respond to gentle touch and engage the insula and cortical regions involved in social-emotional processing. Palm brushing was the control condition because those afferents do not innervate the palm. The description says that the investigators expected greater oxytocin-related increases in brain reactivity during forearm brushing than during palm brushing.

In general, fMRI BOLD contrast is an indirect measure of changes in brain activity. It is used to compare responses across task conditions and drug sessions, not to directly measure a participant’s feelings or establish a clinical outcome. The registry record does not report the numerical mean, confidence interval, or an inferential comparison for the primary endpoint, so the observed response and its precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a continuous outcome summarized as a mean, with a 95% confidence interval specified for dispersion. A mean describes the average value in the analyzed observations. In general, a confidence interval communicates uncertainty around that estimate under the model and sampling assumptions used. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on what quantity was estimated and how the analysis was conducted. In this case, the registry record does not report the mean or interval endpoints, so neither the estimate nor its precision can be examined.

What comparison was intended?

The endpoint description refers to BOLD responses in oxytocin versus placebo sessions and to responses during forearm versus palm brushing. The forearm condition was intended to stimulate C-tactile nerves, while the palm condition was the control. A comparison involving both conditions could be framed as the difference between drug-session responses across the two brushing conditions. The registry record does not specify the exact contrast or model used, so that general description should not be mistaken for a verified statistical estimand.

The design labels do not fully clarify the analysis structure. Randomized, double-masked, and parallel are recorded as design features, but the arm descriptions instead describe a blinded, counterbalanced within-subjects arrangement in which participants received both nasal sprays across two sessions. In a within-subject analysis, observations from the same participant are related and the statistical model should account for that dependence. In a parallel analysis, each participant contributes to an assigned condition, and the comparison is between groups of participants. The record does not state how the discrepancy was resolved or which analysis was used.

Why does the analysis structure matter?

Measurements from the same participant are usually correlated rather than independent. A suitable within-subject method can account for that relationship and compare condition responses while reflecting participant-level variation. Treating correlated observations as independent can misstate uncertainty. Conversely, an analysis intended for independent groups may not represent a crossover or repeated-measures design appropriately. These are general statistical considerations; the registry record does not identify the fitted model or its assumptions.

The task includes more than one brain region and more than one brushing condition, and the record lists 8 outcome measures. When investigators assess multiple outcomes or contrasts, the chance of at least one apparently unusual finding can increase if each is tested separately without a plan for multiplicity. In general, multiplicity approaches may control error rates or distinguish primary from exploratory analyses. The registry record does not state whether any adjustment or hierarchy was prespecified, and it does not report analysis-level results.

How should small enrollment affect interpretation?

With enrollment of 11, estimates may be sensitive to individual observations, and confidence intervals may be wide. This is a general concern rather than a claim about the unreported interval in this trial. The record does not provide the number of participants contributing usable endpoint data, a sample-size justification, or a precision target. It is therefore not possible to determine from the registry whether the study was designed to estimate a particular effect with a specified level of precision.

The record includes a planning assumption describing an illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence that a study had a particular probability of detecting an effect after it was completed. The registry record does not report a trial-specific sample-size justification, and no numerical planning results are stated in the record details.

What can be inferred from the posted statistical information?

The record gives the outcome’s intended scale and summary measure, but no endpoint estimate, interval, test statistic, or p-value. It reports 0 analyses in the registry and does not specify the primary model, covariates, handling of repeated observations, missing-data method, or analysis population beyond saying that data for all enrolled are summarized. These are distinct pieces of information: knowing that an outcome is summarized for all enrolled does not reveal whether every participant had complete measurements or how incomplete observations were handled.

In general, a complete statistical interpretation would require a clearly defined contrast, the analysis population, the estimated effect, its uncertainty, and the method used to obtain them. For repeated-session neuroimaging data, details about within-participant correlation and the exact task contrast would also be important. Because those results and methods are not reported in the registry record, the statistical interpretation remains limited to describing the planned measurement and the uncertainty in the available documentation.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 8 outcome measures, including salivary oxytocin as a secondary outcome, but records 0 analyses. It does not state whether the primary endpoint was tested in a prespecified hierarchy, whether secondary outcomes were exploratory, or whether any adjustment for multiple outcomes or contrasts was used. The endpoint description mentions several brain regions and task conditions, which makes a clearly defined primary contrast especially relevant. The exact number of inferential tests conducted is not reported in the registry record.

In general, testing multiple outcomes or comparisons can increase the chance of a false-positive finding if each is interpreted without regard to the total set of analyses. Prespecification and multiplicity procedures help explain how results should be interpreted across a family of tests. Since no analysis results or multiplicity plan are described in the record, it is not possible to assess how this issue was handled.

Missing-data methods are also not reported in the registry record. The primary outcome states that data for all enrolled participants are summarized, but this does not establish that all enrolled participants contributed complete fMRI data at every relevant visit or condition. The record does not describe the extent or reasons for missing measurements, exclusions, imputation, or sensitivity analyses.

The registry also does not provide a detailed definition of the analysis population. It does not say whether the primary analysis included all randomized participants, only participants with usable scans, or another population. Although the outcome description says all enrolled are summarized, the relationship between enrollment and the analyzed set is not detailed. These omissions prevent a full assessment of selection effects and the robustness of the reported results; in this case, numerical primary results are not reported in the registry record in any event.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The adverse-event record lists adults with PTSD and trauma-exposed adults without PTSD. For adults with PTSD, 9 participants are listed at risk for serious events and 0 serious events are reported; 9 are listed at risk for other events and 0 other events are reported. For trauma-exposed adults without PTSD, 2 participants are listed at risk for serious events and 0 serious events are reported; 2 are listed at risk for other events and 0 other events are reported. Deaths are reported as 0 in both groups.

These are event counts in the registry record, not estimates of comparative risk. The record does not provide an adverse-event comparison between oxytocin and placebo, nor does it show separate exposure-specific counts for the two sessions. Healthy controls are not listed in these adverse-event groups, so their safety figures are not available in this record. No serious-event terms are listed.

A reported count of 0 means that no event of that category is recorded for the listed group; it does not establish that an event could not occur or that the intervention has no safety risks. The groups are small, and the registry record gives no additional detail about collection methods, follow-up completeness, severity definitions, or attribution to a study condition. The figures should therefore be read as the adverse-event counts posted for these groups, not as evidence for a broader safety conclusion.

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

The record supports a description of the study question and its measurement strategy: investigators planned to compare fMRI responses during oxytocin and placebo sessions, using forearm and palm brushing as task conditions relevant to affective processing. It also identifies the anterior insula as the named primary region and describes broader interest in fear/threat and reward-related regions. These details explain what the study set out to measure, not what the results were.

No numerical primary-outcome estimate, confidence interval, or inferential comparison is reported in the registry record. As a result, the posted results do not establish whether the measured response increased, decreased, or was similar across conditions. They also do not indicate how precise an estimate was or whether any observed pattern differed across the PTSD, trauma-exposed/no-PTSD, and healthy-control groups. The expectation stated in the endpoint description is not an observed finding.

Even if a numerical fMRI result were available, BOLD activation would be a task-related brain signal, not a direct measure of clinical benefit or an individual’s experience. In general, statistical evidence about a brain-response contrast does not by itself establish a change in symptoms or broader functioning. The registry description lists the purpose as examining behavior, cognition, and brain function, but the primary measure is the fMRI response.

The design ambiguity further limits interpretation. The record labels the study parallel while describing a within-subject, counterbalanced arrangement. Without knowing the analysis structure and the precise contrast, readers cannot determine how the primary comparison was estimated. Enrollment was 11, and the registry does not provide a sample-size justification, usable endpoint count, or missing-data approach. These omissions make it difficult to assess precision and generalizability.

Accordingly, the registry record documents a research question and a planned neuroimaging measure, but does not provide enough statistical results to judge the direction, magnitude, or uncertainty of the primary finding. It should not be read as establishing a treatment effect or as demonstrating the absence of one.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a registry can describe a detailed measurement rationale without presenting the data needed to evaluate the primary comparison. The outcome description specifies the brain signal, task conditions, and scientific rationale, and identifies a mean with a 95% confidence interval as the intended summary. Yet the registry record does not report the mean, interval, or test result. A detailed endpoint definition cannot substitute for an effect estimate and its uncertainty.

The record also illustrates why consistency among design descriptions matters. Randomized and parallel labels suggest one comparison structure, while the arm descriptions specify both oxytocin and placebo sessions for participants in a blinded, counterbalanced within-subjects arrangement. These structures have different implications for dependence between observations and for the statistical model. Clear reporting of the implemented design and estimand would help readers understand what the comparison represents.

Small enrollment is another important context. With 11 participants, transparent reporting of the analyzed sample and uncertainty would be particularly useful. The record does not give a sample-size justification or disclose how many participants contributed complete primary-outcome data. It also lists multiple outcome measures but does not describe a multiplicity strategy or provide analysis results. These details are central to evaluating precision and the risk of selective interpretation.

The trial therefore matters statistically not because the registry permits a definitive assessment of the primary result, but because it makes visible the distinction between a planned measurement, an analysis, and a reported finding. Reproducible interpretation depends on a clearly specified comparison, complete methods, and numerical estimates with uncertainty. Those elements are not available in the posted outcome information.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations arise specifically from the registry record. First, no numerical primary-outcome result is reported. The record gives the endpoint title, measurement scale, summary type, and confidence-interval level, but not the estimated mean, interval endpoints, or statistical test. The primary effect and its precision therefore cannot be assessed.

Second, the design descriptions are not aligned. The registry identifies a randomized, double-masked parallel model, whereas the arm descriptions state that participants in each group received oxytocin and placebo in a within-subjects design across two blinded, counterbalanced sessions. The record does not explain this difference, so the intended and implemented comparison structure cannot be established from the registry alone.

Third, enrollment was 11, and the record does not report the number with usable fMRI measurements or the number contributing to each relevant condition. It says that data for all enrolled are summarized, but does not describe missing observations, exclusions, or the analysis population. No sample-size justification is reported in the registry record.

Fourth, the endpoint description refers to multiple brain regions and task conditions, and the record lists 8 outcome measures. It does not state how the primary contrast was defined in the analysis, how repeated observations were handled, or whether multiplicity was addressed. The registry lists 0 analyses, so no analysis-level estimates or methods can be reviewed.

Finally, adverse-event figures are available only for the adults with PTSD and trauma-exposed/no-PTSD groups. The registry does not provide condition-specific safety counts, detailed follow-up information, or adverse-event methods. These reporting limits restrict interpretation of both the efficacy-related measurement and the safety record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Oxytocin and Affect Processing in Posttraumatic Stress Disorder — NCT02546570.
• Registry record last updated 2020-04-08; status last verified 2020-03.
• Results first posted 2020-04-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

This completed phase 2 trial enrolled 11 participants and is registered as randomized, double-masked, and parallel. The record describes adults with PTSD, trauma-exposed adults without PTSD, and healthy adult controls. It lists intranasal oxytocin and placebo, with arm descriptions specifying 24 IU and a blinded, counterbalanced within-subjects arrangement across two laboratory sessions.

The primary outcome is an fMRI measure titled change in the anterior insula region, summarized as a mean with a 95% confidence interval. The task contrasts gentle forearm brushing with palm brushing and concerns BOLD responses relevant to affective processing. Salivary oxytocin is listed as a secondary outcome, and 8 outcome measures are recorded.

No numerical primary-outcome estimate, confidence interval, or analysis result is reported in the registry record. The registered parallel model and within-subject arm descriptions are not reconciled, and detailed analysis, missing-data, and multiplicity methods are not reported. The adverse-event record lists 0 serious events, 0 other events, and 0 deaths in each of the two groups for which safety figures are shown.