D-cycloserine Adjunctive Treatment for Posttraumatic Stress Disorder (PTSD) in Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for D-cycloserine Adjunctive Treatment for Posttraumatic Stress Disorder (PTSD) in Adolescents (NCT01157429), a randomized phase 2 study. The primary outcome is Child PTSD Symptom Scale (CPSS).

2. Clinical Question

The study's stated purpose was to assess whether D-cycloserine in combination with CBT was more effective than CBT plus placebo for reducing PTSD symptoms. The outcome is a continuous symptom score, with higher scores indicating greater symptom severity. Consequently, the clinical question concerns the difference in average symptom scores between the randomized arms at the specified assessment, rather than a count of participants who did or did not meet a threshold.

The registry record lists the mean CPSS scores as 20.4 for D-cycloserine plus CBT and 11.0 for placebo plus CBT. Those posted summaries describe the observed scores, but the record does not report an inferential comparison or a confidence interval. The means therefore cannot, on their own, establish how precisely the between-arm contrast is estimated or whether the observed difference is compatible with chance variation. Further details about how the primary comparison was intended to be analyzed are not reported in the registry record.

3. Trial Design

This is a completed phase 2, randomized, parallel-group trial sponsored by Tulane University School of Medicine. The registry record lists quadruple masking. It records a planned enrollment of 24 participants, with study start in 2010-06 and primary completion in 2012-06. Those dates describe the registered study timeline; they do not establish when each participant was assessed.

The two arm descriptions share trauma-focused CBT and differ in the pill given alongside therapy. The D-cycloserine arm is described as receiving 12 sessions of manualized trauma-focused CBT plus seven doses of D-cycloserine. The placebo arm is described as receiving 12 sessions of trauma-focused CBT plus seven doses of placebo pill. The registry lists CBT as a behavioral intervention, and D-cycloserine and placebo pill as drug interventions. The record does not report further details about dose, dosing schedule, treatment adherence, or how masking was maintained.

For the primary outcome, the posted arm summaries each have an outcome sample size of 8. The adverse-event summaries use 12 participants at risk in each arm. These figures represent different reported denominators; the registry record does not explain the difference between the planned enrollment, the outcome sample sizes, and the safety denominators. It also does not report participant flow, exclusions, withdrawals, or the number randomized to each arm.

A randomized parallel design is generally intended to compare groups assigned to different treatment strategies, with participants remaining in their assigned groups for the comparison. General methodological interpretation depends on how randomization, follow-up, and analysis were conducted. The registry record identifies randomization and the parallel model, but does not report the sequence-generation method, allocation concealment, the analysis population, or whether outcomes were analyzed according to assigned group.

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: A total of 63 youth were assessed. Only 47 meet all the inclusion and exclusion criteria and were offered treatment. Of those 47, only 24 were retained through session 5 of the treatment, which was the point of random allocation. Twenty-three subjects of the 47 subjects who were offered treatment dropped out prior to session 5.

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 Child PTSD Symptom Scale (CPSS), measured over After 12 therapy sessions, up to 28 weeks..

The primary endpoint is the Child PTSD Symptom Scale (CPSS), reported as a mean total score in units on a scale. The registry describes the CPSS as a 17-item standardized, self-administered questionnaire with versions for youths and caregivers. Items are scored on a 0-3 scale; the minimum possible total is 0 and the maximum is 51. Only the total score is used, with no subscales. A higher score indicates greater symptom severity, described in the registry as worse.

The measure is used to represent PTSD symptom severity in a form that can be summarized across participants and compared between randomized groups. A mean retains information about the range of total scores rather than reducing the outcome to a binary status. That can be useful for assessing the overall symptom burden recorded by the scale, while still requiring care in interpretation: the mean does not show how scores are distributed among individuals, and it does not identify how many participants improved or worsened.

The registry specifies the assessment timeframe as after 12 therapy sessions, up to 28 weeks. It does not report which questionnaire version contributed to the posted scores, who completed it, or whether the timeframe varied across participants. The posted primary outcome is presented as a mean with standard deviation in each arm. The record does not report a confidence interval or a formal statistical comparison for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical concepts help distinguish the information in the posted summaries from the information needed for an inferential comparison. The registry record reports arm means and standard deviations for a continuous outcome, but does not report an analysis comparing the arms. These summaries answer different questions from a treatment-effect estimate, a confidence interval, or a hypothesis test.

What do the mean and standard deviation describe?

General: the mean is the arithmetic average of the observed scores in a group. It gives a concise description of the group's central score, but does not show every participant's score or the shape of the score distribution. The standard deviation describes how dispersed the observed scores are around their group mean. A larger standard deviation indicates more variation among the observed scores, but it does not directly measure uncertainty in the estimated mean.

For the CPSS, a higher value represents greater symptom severity. The reported means are 20.4 for D-cycloserine plus CBT and 11.0 for placebo plus CBT, while the standard deviations are 9.7 and 8.9. Each outcome group has a reported sample size of 8. These descriptive summaries do not tell whether the observed difference between means is statistically distinguishable from random variation. They also do not show whether the individual score distributions overlap, whether the means are influenced by extreme observations, or how complete follow-up was.

What would a confidence interval add?

General: a confidence interval presents a range of values that are compatible with the data and the assumptions of the specified statistical method. For a treatment comparison, it communicates uncertainty about the estimated contrast as well as its direction and magnitude. A narrow interval indicates greater precision under the model; a wide interval indicates less precision. An interval does not guarantee that the true value lies within its endpoints, and its interpretation depends on the analysis and assumptions used.

A confidence interval for the difference between CPSS means is not reported in the registry record. The separate standard deviations are not substitutes for that interval. They describe variability within the arms, whereas the precision of a comparison also depends on the sample sizes, the analysis method, and any model assumptions. Because the registry record gives no inferential comparison, the uncertainty around the between-arm estimate cannot be assessed from the posted summaries alone.

What would a p-value answer?

General: a p-value is calculated under a specified statistical model and null hypothesis. It describes how incompatible the observed data, or data more extreme, would be with that null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A p-value is most informative when read with an effect estimate, its confidence interval, and a clear description of the analysis.

No p-value for the primary comparison is reported in the registry record. The registry lists zero analyses, and the posted continuous outcome lacks an estimable two-arm comparison. It would therefore be inappropriate to infer statistical significance from the difference between the displayed means or to calculate a test result from the summaries in place of the trial's own analysis.

Why can small samples and variable scores matter?

General: when groups are small, estimates can be imprecise and sensitive to the scores of individual participants. Variation in outcome scores adds uncertainty to a comparison. A standard deviation is useful for describing that variation, but it does not resolve uncertainty about the treatment contrast. Small samples can also make it difficult to evaluate modeling assumptions or describe differences in the outcome distribution reliably.

General: over-dispersion refers to observed variability greater than a statistical model expects. It matters because a model that understates variability can produce uncertainty estimates that are too small. The CPSS is reported as a continuous measure with standard deviations, but the registry record does not state that an over-dispersion issue was evaluated or that a particular model was used. No claim about the adequacy of a specific model can therefore be made.

How should planning illustrations be read?

General: sample-size calculations depend on design assumptions, including the significance level, allocation, the effect selected for detection, and the statistical method. The registry's planning illustration description specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. These are assumptions for the illustration, not evidence about the trial's observed power.

The illustrations are based on the observed effect rather than the trial's own documented design justification. They should be read as planning scenarios, not as a retrospective measure of success and not as a substitute for an inferential result. The registry record does not report the trial's sample-size justification or the analyses that were planned in its protocol. No sample-size values beyond those in the posted planning material are asserted in this explanation.

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("D-cycloserine Plus CBT", "Placebo Pill")
n   <- c(8, 8)
m   <- c(20.4, 11)
sp  <- c(9.7, 8.9)
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  D-cycloserine Plus CBT  8  20.400  9.700  12.291  28.509
CARM  Placebo Pill  8  11.000  8.900  3.559  18.441

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when several outcomes, comparisons, time points, or analyses are tested. Repeated testing can increase the chance of a seemingly notable result arising by chance, so trial plans may specify a primary outcome and an approach to controlling or interpreting multiple comparisons. The registry record lists one outcome measure and zero analyses. It does not report secondary posted outcomes, a multiplicity adjustment, or a detailed analysis plan. There is therefore no basis in the registry record to determine whether multiple analyses were planned or how they would have been handled.

Missing data are also important for interpreting a randomized comparison. If outcome measurements are unavailable for some randomized participants, the observed participants may not represent the full randomized groups. The registry record reports an outcome sample size of 8 in each arm, while planned enrollment is 24 and the safety summaries report 12 participants at risk in each arm. It does not report participant flow, reasons for missing outcome measurements, missing-data assumptions, or any method used to account for missing values. The difference among these reported denominators cannot be explained from the registry record.

The record does not identify the analysis population, such as whether all randomized participants were included according to assigned group, nor does it report a per-protocol or other analysis population. It also does not report whether any adjustment for baseline measures was planned or used. These details affect the interpretation of an estimated treatment comparison. With no posted inferential analysis and no account of missing outcomes, the descriptive means should not be treated as a complete analysis of all randomized participants.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports serious adverse event figures for 12 participants at risk in each arm. There were 0 serious adverse events reported for D-cycloserine plus CBT and 0 for placebo pill plus CBT. These are the counts recorded in the registry; they do not establish that serious events were impossible or that no other safety information exists. The record does not list serious adverse event terms.

For other adverse events, the registry reports 1 in the D-cycloserine plus CBT group and 2 in the placebo pill group, with 12 participants at risk in each. The record does not provide event descriptions, severity, timing, relatedness to treatment, or information about whether participants could have experienced more than one event. It also does not report deaths; the death fields are not populated, so the number of deaths is not reported in the registry record.

General: event counts are descriptive safety data. Their interpretation depends on the definitions used, the period of observation, and how events were collected and attributed. With these summaries alone, the event counts should not be converted into a comparative safety conclusion. The registry does not report a statistical comparison of adverse events, and the listed denominators differ from the outcome sample sizes. The available figures describe only the events and participants recorded in these safety summaries.

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

The result is a set of descriptive primary-outcome summaries from a randomized, parallel-group phase 2 trial in adolescents with PTSD. The posted mean CPSS score is 20.4 for D-cycloserine plus CBT and 11.0 for placebo plus CBT. Since a higher CPSS score indicates greater symptom severity, the arm means are ordered in the direction of greater recorded severity for the D-cycloserine arm. This statement describes the observed summaries; it is not a conclusion that the intervention caused a difference.

The record does not report an inferential comparison, confidence interval, or p-value for the primary outcome. It is therefore not possible to tell from the record how precise the between-arm contrast is or how compatible the results are with chance variation under a specified model. The small outcome group sizes and the absence of participant-level results or missing-data information further limit interpretation. The study's reported enrollment, outcome denominators, and safety denominators are not interchangeable, and the registry does not explain their relationship.

The result also does not establish whether the therapy strategies differ in clinical importance, whether any individual participant experienced a meaningful change, or whether results apply to people outside the population studied. The registry record does not report a threshold for meaningful change, baseline CPSS scores, secondary outcomes, or longer-term follow-up results. The listed timeframe concerns the post-treatment assessment after 12 therapy sessions, up to 28 weeks.

Accordingly, the appropriate reading is narrow: the registry records two arm-level outcome means and their standard deviations, but does not provide the analysis needed to support a statistical conclusion about the treatment comparison. The available summaries should not be used to claim that D-cycloserine improves or worsens PTSD symptoms, nor to make a treatment recommendation.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a registered study design and a fully reported treatment comparison. The record identifies a randomized parallel-group design and a continuous primary endpoint, and it provides arm-level means, standard deviations, and outcome sample sizes. Those details describe the observed data at a basic level, but they do not by themselves provide an estimate with quantified uncertainty.

The distinction matters because readers can easily overinterpret different arm means. A numerical separation between two sample means is descriptive; an inferential comparison needs a defined analysis and a measure of uncertainty. The registry record reports neither a confidence interval nor a p-value for the primary comparison. Without these, readers cannot judge the precision of the contrast or determine how it relates to a prespecified statistical question.

The record also illustrates why denominators need context. Planned enrollment is 24, the primary-outcome summaries have 8 participants per arm, and the adverse-event summaries each list 12 participants at risk. Each figure pertains to a different part of the record, and the reasons for the differences are not reported. Transparent participant flow and analysis-population definitions would help readers understand which participants contributed to each result.

Finally, the registry describes planning illustrations based on the observed effect, while the trial's own sample-size justification and analysis plan are not reported in the registry record. Keeping retrospective planning scenarios separate from evidence about the completed trial prevents an illustration from being mistaken for observed power. The statistical value of the record is therefore chiefly descriptive, while the missing inferential details limit conclusions about the primary comparison.

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 primary limitation is that the registry record does not report a two-arm inferential comparison for the continuous primary endpoint. Although it gives means, standard deviations, and outcome sample sizes, it does not provide an estimated contrast with a confidence interval or a p-value. The posted summaries therefore do not quantify uncertainty around the difference between arms.

Outcome data are reported for 8 participants in each arm, while the registered enrollment is 24 and the adverse-event summaries list 12 participants at risk in each group. The record does not explain these different denominators or report participant flow, withdrawals, exclusions, or reasons for missing primary-outcome data. It also does not report an analysis population or a missing-data method. These omissions prevent assessment of how representative the outcome summaries are of the randomized groups.

The registry record does not report baseline CPSS scores, individual participant scores, a threshold for meaningful change, or results at additional time points. It does not identify which CPSS respondent version was used for the posted endpoint. Consequently, the record does not support assessment of baseline comparability, individual change, outcome distribution, or persistence of the observed scores.

Details of randomization implementation, allocation concealment, masking procedures, treatment adherence, dose schedule, and the statistical analysis plan are not reported in the registry record. The sample-size justification and any adjustment for multiple analyses are also not reported. These limitations are specific to the information available in the registry; they do not establish that such procedures were absent from the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: D-cycloserine Adjunctive Treatment for Posttraumatic Stress Disorder (PTSD) in Adolescents — NCT01157429.
• Registry record last updated 2017-06-06; status last verified 2017-04.
• Results first posted 2017-06-06.
• 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 a completed phase 2 randomized, quadruple-masked, parallel-group study sponsored by Tulane University School of Medicine. It compares D-cycloserine plus trauma-focused CBT with placebo plus trauma-focused CBT in adolescents aged 13-18 with PTSD. Planned enrollment is 24, and the listed study dates are 2010-06 to 2012-06.

The primary endpoint is mean total CPSS score after 12 therapy sessions, up to 28 weeks. The posted means are 20.4 with standard deviation 9.7 for D-cycloserine plus CBT and 11.0 with standard deviation 8.9 for placebo plus CBT; each arm has an outcome sample size of 8. Higher CPSS scores indicate greater symptom severity.

The registry does not report an inferential comparison for the primary endpoint, a confidence interval, or a p-value. Safety summaries list 0 serious adverse events in each group and other adverse event counts of 1 and 2, with 12 participants at risk per group. Reasons for the different denominators, analysis populations, missing-data handling, and the trial's statistical plan are not reported in the registry record.