Oxytocin vs. Placebo for the Treatment Hyperphagia in Children and Adolescents With Prader-Willi Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oxytocin vs. Placebo for the Treatment Hyperphagia in Children and Adolescents With Prader-Willi Syndrome (NCT02629991), a randomized phase 2 study. The primary outcome is Hyperphagia Questionnaire (HQ)- Total Score.

2. Clinical Question

3. Trial Design

The registry classifies this as a randomized, parallel, phase 2 trial with quadruple masking. The study summary describes a randomized, double-blind, 8 week treatment trial. These are the registry’s descriptions; a more detailed account of who was masked, how randomization was generated, or how allocation was concealed is not reported in the registry record.

The planned comparison was intranasal oxytocin versus matched placebo in children and adolescents with Prader-Willi syndrome. The registry lists enrollment of 23, while the study summary describes an intended sample of 24 subjects aged 5 to 18 years. The reason for the difference between intended and listed enrollment is not reported in the registry record. The listed sponsor is Montefiore Medical Center. The study started in 2015-10, had primary completion in 2016-12, and is marked completed.

Both groups were instructed to use the same stated administration schedule: 16 IU per day every day, with 2 puffs per nostril and 4 IU per puff. The assigned intervention differed by whether the nasal preparation was oxytocin or matched placebo. The record describes assessment of eating behaviors, repetitive and disruptive behaviors, and salivary oxytocin levels. It lists several Repetitive Behavior Scale-Revised factors as secondary outcomes. Further details of visit procedures, adherence measurement, and the operational schedule for collecting each measure are not reported in the registry record.

The design is suitable for a randomized comparison in principle, but interpretation depends on the results and analysis details. Arm-level outcome estimates, the statistical model, and the handling of repeated measurements are not reported in the registry record. Therefore, the design description alone does not establish the size, precision, or direction of any difference between groups.

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: 1 subject discontinued oxytocin early and 1 subject discontinued placebo early

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 Hyperphagia Questionnaire (HQ)- Total Score, measured over Assessed trends over multiple time points (weeks 0, 2, 4, 6, and 8), week 0 (baseline), week 4 and week 8 are reported..

The primary endpoint was the Hyperphagia Questionnaire total score, a clinician-rated measure intended to capture food-related behaviors in people with Prader-Willi syndrome. Its 11 items map to the Hyperphagic Behavior, Hyperphagic Drive, and Hyperphagia Severity subscales, which are summed to form the total score. The score ranges from 11 to 55; higher scores indicate more hyperphagia and a worse outcome.

This type of measure is useful because the clinical question concerns eating-related behavior, rather than a laboratory value alone. A total score combines related aspects of the construct into one measure, while the subscales describe distinct components. The total score can therefore provide a broad summary, but it may not show which component is responsible for a change. The registry record does not report subscale results for the primary measure.

The record describes assessment over multiple time points: weeks 0, 2, 4, 6, and 8, with week 0 as baseline and results identified for week 0, week 4, and week 8. The primary outcome is thus longitudinal rather than a measure at one isolated visit. The registry record does not report numeric means, standard deviations, or a clearly isolated between-group contrast for this endpoint. Without those estimates, the amount and precision of any observed change cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean with standard deviation. It also identifies assessment at multiple visits. The specific statistical model used for the repeated measurements, any adjustment variables, and the exact contrast used for the primary analysis are not reported in the registry record. The following concepts are general statistical context, not a description of an analysis confirmed for this trial.

What does a mean describe?

General statistical context: a mean is a measure of the center of a set of scores. In a randomized trial, arm-specific means can describe the average score among participants assigned to each group at a particular assessment. A mean by itself does not describe how variable individual scores are, nor does it show the uncertainty in a comparison between groups. The registry identifies the standard deviation as the measure of dispersion for the primary outcome, but numeric means and standard deviations are not reported in the registry record.

General statistical context: the standard deviation describes spread among individual observations around their mean. It is not the same as a standard error or a confidence interval. A standard deviation concerns variation among scores; a confidence interval concerns uncertainty around an estimate, such as a mean or a between-group contrast. The registry record does not report a confidence interval for the primary outcome.

Why is a between-group estimate important?

General statistical context: random assignment makes the comparison between assigned groups central to estimating a treatment contrast. A difference in change within one group does not by itself show how that change compares with the other group. A between-group estimate gives the direction and magnitude of the contrast, while a confidence interval communicates the range of values compatible with the data under the analysis assumptions. Without an estimate and its uncertainty, a reader cannot assess either the magnitude or precision of the comparison.

The primary outcome was assessed repeatedly. General statistical context: repeated measurements on the same participant are related, so treating each visit as if it came from a different participant can misrepresent the information in the data. Longitudinal approaches can model the pattern over time and account for within-participant correlation. Different approaches may target an overall group difference, a difference at a selected visit, or a difference in trajectories. The registry record does not report which target or model was used.

How should multiple time points be understood?

General statistical context: when an outcome is measured at several visits, there may be more than one possible comparison. A prespecified primary time point or a prespecified overall contrast can help make the analysis interpretable. If several contrasts are examined, the chance of at least one apparently unusual result can increase unless the analysis accounts for multiplicity or clearly distinguishes primary from exploratory analyses. The registry record describes trends across weeks 0, 2, 4, 6, and 8 and identifies week 0, week 4, and week 8 as reported, but does not provide a single numerical primary comparison or the analysis plan for these visits.

General statistical context: a p value, when reported, describes how compatible the observed data are with a specified null hypothesis under the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. A confidence interval is often more informative for interpretation because it shows the estimate’s precision and the range of values compatible with the data. Neither a p value nor a confidence interval for the primary comparison is reported in the registry record.

What does the planning illustration represent?

The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The stated effect to detect is a share of the observed effect. These are planning assumptions, not the trial’s reported design justification, and the resulting planning values are not included in the registry record for this explanation. A planning illustration asks how many participants per arm might be required under specified assumptions; it does not describe the number actually observed or establish the trial’s observed power.

General statistical context: planning calculations are conditional on assumptions about the target effect, variability, allocation, and analysis. If the observed effect is used as the starting point, the illustration is retrospective and should not be confused with a prospectively justified sample size. A calculated number of participants per arm is not evidence that the actual trial had adequate precision, and it is not an outcome result. The registry record does not report a protocol sample-size justification or enough numerical results to assess the precision of the primary estimate.

The registry lists 10 outcome measures and 10 analyses. General statistical context: multiple outcomes and analyses can raise questions about which result was primary and whether multiplicity was handled. The record names the primary measure and lists several secondary outcomes, but the analysis plan and any adjustment approach are not reported in the registry record. No statistical test or model should be attributed to the investigators beyond what the registry explicitly describes.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome was assessed over multiple time points, with weeks 0, 2, 4, 6, and 8 identified for assessment and week 0, week 4, and week 8 identified as reported. The registry record does not reduce this set to one comparison. It also lists 10 outcome measures and 10 analyses, along with six Repetitive Behavior Scale-Revised factor scores as secondary outcomes. These registry entries make the choice of primary contrast and the handling of multiple comparisons important to interpretation.

The registry record does not report whether the analysis plan controlled the overall false-positive risk, used a hierarchy of outcomes, or treated some comparisons as exploratory. It also does not report whether the primary endpoint was defined by a particular visit or by a combined longitudinal estimate. Without that information, a reader cannot determine how to interpret a result selected from multiple outcomes or time points. Numeric outcome results are not reported in the registry record, so multiplicity cannot be evaluated from the results themselves.

The primary outcome population description notes one early discontinuation in the oxytocin group and one in the placebo group. The registry record does not report the number of participants with observed measurements at each visit, reasons for missing outcome measurements beyond these early discontinuations, or the method used to handle missing data. It does not report whether the analysis used all randomized participants, participants who completed treatment, or another analysis population. These omissions limit assessment of how representative the analyzed data may be of randomized participants and whether conclusions depend on assumptions about missing measurements.

General statistical context: missing-data methods rely on assumptions about why observations are missing and how missing outcomes relate to observed data. Different assumptions can lead to different estimates. The methods and sensitivity analyses used in this trial are not reported in the registry record, so no particular approach can be inferred.

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.

Most frequent non-serious adverse event terms

The registry lists 11 participants at risk for serious adverse events in the intranasal oxytocin group and 12 in the matched placebo group. It reports 0 serious adverse events in each group and 0 deaths in each group. These are the serious-event and death counts recorded for the groups; they do not describe the primary outcome or the trial’s efficacy comparison.

The record separately lists 7 participants affected by other adverse events in the oxytocin group and 7 in the placebo group, with 11 and 12 participants at risk, respectively. The record does not provide the event terms or further detail about severity, duration, or relation to treatment. No serious adverse event terms are listed.

General statistical context: a count of zero observed serious events does not demonstrate that the underlying risk is zero. Safety counts are most informative when read alongside the number of participants observed, the duration of follow-up, event definitions, and the completeness of reporting. This trial’s listed enrollment and treatment period describe a limited observation context, and the record does not report additional follow-up details for these counts. The figures should therefore be read as the adverse-event counts recorded for this trial, not as proof that serious events cannot occur.

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

The record establishes that investigators conducted a randomized, parallel phase 2 comparison of intranasal oxytocin with matched placebo in children and adolescents with Prader-Willi syndrome. It identifies a clinically relevant behavioral measure, the Hyperphagia Questionnaire total score, and describes repeated assessment during an 8 week treatment period. It also records the planned treatment instructions, several secondary behavioral outcomes, and adverse-event counts.

What the record does not establish is the size or direction of the primary outcome contrast. Numeric arm-level scores, a between-group estimate, and a confidence interval are not reported in the registry record. Without these, there is no basis for describing how much the groups differed, how precisely the contrast was estimated, or whether the observed data were compatible with a range of potentially important effects. The record therefore does not support a statistical conclusion about the primary comparison.

The enrollment of 23 and the early discontinuations noted in the primary outcome population also do not determine the effective information available for every assessment. The registry record does not describe the analysis population, the completeness of repeated measurements, or the handling of missing data. These details are needed to understand the consequences of discontinuations for the longitudinal comparison.

The safety information records no serious adverse events or deaths in either group, alongside other adverse events affecting 7 participants in each group. Such counts describe what was recorded in this trial; they are not a guarantee about safety in other settings or populations. More detailed event descriptions and longer-term follow-up are not reported in the registry record.

Overall, the record documents a small randomized study and its intended outcome framework, but the missing primary numerical results prevent a quantitative assessment of treatment differences. No conclusion that the intervention does or does not change hyperphagia follows from the design description alone.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a randomized design and an interpretable estimate of a treatment contrast. Randomization describes how groups are formed, while outcome estimates and their uncertainty are needed to assess what the comparison shows. The registry identifies the randomized groups and a primary behavioral outcome, but numeric primary results are not reported in the registry record. Readers therefore cannot evaluate the magnitude or precision of the contrast.

The repeated-measures structure is another important feature. Hyperphagia Questionnaire scores were assessed across several visits, and the record describes trends over time. A longitudinal outcome can be examined in several ways, including comparisons at a selected visit or comparisons of patterns over time. The registry does not report which analysis was used or identify one numerical primary contrast. That makes it difficult to connect the stated endpoint to a single inferential result.

The trial also has a limited listed enrollment of 23, while the summary describes an intended sample of 24. A small study can still be informative, but the uncertainty around its estimates becomes especially important. Without numerical estimates and intervals, readers cannot distinguish a precise near-zero contrast from an imprecise estimate that is compatible with a broad range of effects. The registry does not report the protocol sample-size justification.

Finally, the combination of multiple outcome measures, multiple analyses, and repeated assessments makes prespecification and transparent reporting important. The registry lists these outcomes and analyses but does not report how multiplicity was handled. The study is therefore useful as an example of why reporting the analysis target, missing-data approach, estimates, and uncertainty is essential for a clear statistical interpretation.

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.

The main limitation for statistical interpretation is that numeric results for the primary Hyperphagia Questionnaire total score are not reported in the registry record. Arm-level means and standard deviations, a between-group estimate, a confidence interval, and a p value are not reported. This prevents assessment of effect size, precision, or statistical compatibility with a null comparison.

The outcome was assessed at multiple time points, but the registry does not identify one numerical contrast as the primary result. It does not report the longitudinal model, the handling of within-participant correlation, or whether the analysis emphasized a particular visit or an overall trajectory. The relationship between the stated trend assessment and the reported visits is therefore not fully explained in the registry record.

The record lists 23 enrolled participants, while the summary describes an intended sample of 24. It notes one early discontinuation in each group, but does not report outcome availability at each visit, the analysis population, or how missing data were handled. The reason for the enrollment difference is also not reported in the registry record.

The registry names secondary behavioral outcomes and reports counts for serious and other adverse events, but detailed outcome estimates and event descriptions are not reported. The multiplicity plan, protocol sample-size justification, randomization procedures, and masking procedures beyond the registry’s classification are not reported in the registry record. These limitations restrict evaluation of both the analysis and the completeness of the reported evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Oxytocin vs. Placebo for the Treatment Hyperphagia in Children and Adolescents With Prader-Willi Syndrome — NCT02629991.
• Registry record last updated 2021-10-07; status last verified 2021-09.
• Results first posted 2021-10-07.
• 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 compared intranasal oxytocin with matched placebo in children and adolescents with Prader-Willi syndrome. The registry describes randomized, parallel allocation and quadruple masking; the study summary describes an 8 week randomized, double-blind treatment trial. The listed enrollment is 23, and the intended sample described in the summary is 24.

The primary outcome was the Hyperphagia Questionnaire total score, assessed at multiple time points. Higher scores indicate more hyperphagia and a worse outcome. The registry record does not report numeric primary outcome results or one clear between-group estimate. It lists secondary behavioral measures and records 0 serious adverse events and 0 deaths in both groups, with other adverse events affecting 7 participants in each group.

The record documents the trial design and outcome framework, but the missing numerical efficacy results and analysis details prevent quantitative interpretation of the primary comparison.