Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate (NCT04006925), a randomized phase 4 study. The primary outcome is Number of RBD Episodes in One Month (Per Patient RBD Log).

2. Clinical Question

The trial is described as a randomized, placebo-controlled study of sodium oxybate in treatment-resistant RBD. The primary outcome uses participants’ records of dream-enactment episodes, including examples such as talking, shouting, kicking, or punching. It is a count of episodes over a defined observation period, rather than a rating of overall disease severity or a measure of sleepiness.

The registry also lists secondary outcomes involving clinician-rated efficacy and improvement, the Epworth Sleepiness Scale, video-polysomnography measures of episode severity and frequency during REM sleep, and actigraphy measures of movements during sleep. These outcomes broaden the clinical questions beyond episode counts in a patient log. Their results are not reported in the registry record. The primary comparison cannot be characterized from the available record because its multiple categories or time points were not reduced to one comparison, and no primary result is stated.

3. Trial Design

This was a Phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Stanford University. Sodium oxybate was compared with placebo. The registry lists enrollment as 24 and the status as completed. The recorded study start date is 2019-09-10, and the primary completion date is 2022-02-01. The registry record does not report the randomization method, allocation concealment procedures, or the practical details of masking.

The official title describes the study as a randomized placebo-controlled trial in treatment-resistant RBD. The registry lists both RBD and Parkinson disease among the conditions, but further details about the participant population, eligibility criteria, disease duration, and baseline characteristics are not reported in the registry record. The arm descriptions state that sodium oxybate or placebo would be dispensed; dose, dose adjustment, and adherence procedures are not reported in the registry record.

The primary measure is the number of RBD episodes recorded in a patient log. It was assessed for 28 days at baseline and during the last month of treatment, with a total treatment period of up to 12 weeks. The primary outcome population is described as participants with data at each time point. The registry lists seven outcome measures and 14 analyses, but does not report a full statistical analysis plan or explain how each analysis relates to the primary comparison.

The design establishes a randomized placebo comparison, but those design features alone do not determine how the results should be interpreted. Without reported outcome estimates, uncertainty intervals, and details of the analyses, the record cannot establish the size or precision of a treatment contrast. It also does not report whether any interim analyses occurred or give a sample-size justification.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants with data at each time point are included in the analysis

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 Number of RBD Episodes in One Month (Per Patient RBD Log), measured over Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks).

The primary endpoint is the number of RBD episodes in one month, recorded by participants in a per-patient RBD log. The log includes episodes of dream enactment, with examples in the registry such as talking, shouting, kicking, or punching. The endpoint was assessed over 28 days at baseline and during the last month of treatment, which lasted up to 12 weeks.

This measure focuses on the frequency of recorded episodes over a specified period. It can therefore capture changes in the occurrence of dream enactment as experienced and documented by participants. It is distinct from a clinician’s global assessment, a sleepiness questionnaire, video-polysomnography, or actigraphy; the registry lists those as secondary outcomes.

The registry specifies the median and inter-quartile range as the summary format. In general, the median describes the midpoint of ordered observations, while the inter-quartile range describes the spread of the middle portion of those observations. These summaries can be useful for count data, especially when values are unevenly distributed. That is a general statistical rationale, not evidence about the actual distribution in this trial.

The registry record does not report the endpoint values at baseline or during treatment, a treatment contrast, or an uncertainty interval. Participants with data at each time point are included in the stated analysis population; the handling of participants without data at one or both time points is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the study as randomized, quadruple-masked, and parallel-group. In a randomized trial, assignment is intended to create groups that can be compared without choosing treatment on the basis of participants’ characteristics. This general principle does not guarantee that the groups were balanced in every feature, nor does the registry record describe the randomization sequence or allocation concealment. Parallel-group means the comparison is between groups assigned to different interventions, rather than a crossover in which participants receive interventions in sequence. The record does not give further design details.

What does the median and inter-quartile range describe?

The primary measure is a count of RBD episodes logged by each participant. The registry specifies the median and inter-quartile range rather than a mean and standard deviation. In general, the median is the midpoint of ordered observations and is less affected by unusually high or low values than the mean. The inter-quartile range describes the spread of the middle half of ordered values. These are descriptive summaries; they do not, by themselves, quantify a treatment-group difference or the uncertainty around one. The registry record does not report the observed summaries or explain the choice of summary measure.

Why does the observation window matter?

The endpoint was recorded over 28 days at baseline and during the last month of treatment, which lasted up to 12 weeks. Using a defined observation window makes clear what period the episode count represents. In general, counts can depend on how long observations are collected, so comparing counts requires attention to the observation period and to whether data are available for the intended period. The record states the planned windows but does not report completeness of logging, adherence to the observation schedule, or any adjustment for differences in exposure time.

What does the analysis population mean?

The primary outcome population consists of participants with data at each time point. This wording indicates that both time-point records are required for inclusion in the stated analysis. It does not say how many participants met that condition, how missing observations were handled, or whether additional populations were analyzed. In general, an analysis limited to participants with complete measurements can be affected if missingness is related to outcome or treatment. The registry record does not report a missing-data strategy, imputation, sensitivity analyses, or a comparison of included and excluded participants.

How should a treatment comparison be assessed?

A treatment comparison should be interpreted using an estimate of the difference between randomized groups, together with an uncertainty interval and the analysis method. A confidence interval, in general, describes a range of values compatible with the data and the statistical model at a stated confidence level; it is not a guarantee that the true effect lies in that range. A p-value addresses compatibility with a specified null model under the analysis assumptions; it does not measure clinical importance. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

The primary outcome is a count. In general, count data can be analyzed using methods suited to counts, and over-dispersion matters when the observed variation is greater than a model assumes. If a model underestimates variability, its uncertainty estimates may be too narrow. This is general statistical context only: the registry record does not report a count model, a dispersion assessment, covariate adjustment, or the final analysis method. It also does not report whether the analysis used a change from baseline, a treatment-period value, or another contrast.

What do the planning assumptions mean?

The registry describes a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation; it describes the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that an effect was present. They depend on assumptions about the target effect and analysis. The registry record does not report the trial’s own sample-size justification, and the primary outcome was not reduced to one comparison. No calculated sample-size result should be interpreted as a trial outcome or as proof of adequacy.

In general, an analysis plan should clarify the primary contrast, model, handling of missing measurements, and approach to multiple outcomes or tests. Those details help readers assess whether reported estimates correspond to the intended question and how much flexibility existed in analysis choices. The registry record does not report these elements in sufficient detail to reconstruct the primary statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and 14 analyses. It identifies the patient-log count as the primary outcome, alongside secondary outcomes covering clinician-rated response and improvement, sleepiness, video-polysomnography, and actigraphy. However, the primary endpoint includes multiple categories or time points and was not reduced to one comparison. The registry record therefore does not identify a single numerical primary contrast for interpretation.

When a study examines multiple outcomes, time points, or analyses, the chance of finding an apparently notable result can increase if each is tested separately. In general, a prespecified multiplicity strategy can help control the interpretation of multiple tests. The registry record does not report whether any adjustment, testing hierarchy, or other multiplicity strategy was used. It also does not report which of the 14 analyses were prespecified or how results were selected for reporting.

The stated primary analysis includes participants with data at each time point. Missing-data amounts, reasons, imputation, sensitivity analyses, and the treatment of participants who did not contribute data at both time points are not reported in the registry record. The record does not report whether an intention-to-treat population, per-protocol population, or other analysis population was used in addition to the stated population. These omissions limit assessment of how missingness and analysis choices may affect the results.

The statistical analysis plan, including any interim analyses and stopping rules, is not reported in the registry record. It is therefore not possible to determine from the record whether the observed analyses followed a prespecified plan or how uncertainty was handled across the outcome family.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myoclonus episode (8.3%), sleep terror (8.3%), suicidal ideation (8.3%), anxiety (8.3%), dizziness (8.3%).

The registry reports serious adverse events affecting 5 of 12 participants at risk in the sodium oxybate arm and 0 of 12 participants at risk in the placebo arm. It reports other adverse events affecting 7 of 12 participants at risk in the sodium oxybate arm and 2 of 12 participants at risk in the placebo arm. Deaths are recorded as 0 in each arm.

These are counts of affected participants, not a complete account of the number, timing, duration, or severity of every event. A participant can potentially experience more than one event; the record does not describe event overlap or provide exposure-adjusted rates. It also does not report statistical comparisons of the adverse-event figures, so the counts alone do not establish whether a difference is meaningful.

The record lists myoclonus episode, sleep terror, suicidal ideation, anxiety, and dizziness among the serious-event terms, each reported as 8.3%. It does not assign these terms to a treatment arm or provide further context about timing, outcome, or attribution. The terms should therefore be read as registry-listed events, not as evidence that a particular arm had a specific event rate. The posted safety information is descriptive and does not replace a fuller account of adverse events.

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

The registry record establishes that a randomized, placebo-controlled trial of sodium oxybate for treatment-resistant RBD was completed and defines a patient-log measure of episode frequency. It also describes several secondary measures and posts adverse-event counts by arm. These details clarify what was intended to be studied and what safety counts are recorded.

The record does not report the primary outcome values or a between-arm estimate. It therefore does not show the size or direction of any difference in logged RBD episodes, nor how precisely such a difference was estimated. The trial status of completed does not, by itself, supply the missing efficacy results. No conclusion that sodium oxybate did or did not change the primary outcome is supported by the registry information.

The secondary outcomes are likewise named without numerical results in the registry record. Their presence does not establish that a benefit or harm was observed. The serious and other adverse-event counts are descriptive and do not include enough information for a full comparative assessment. In particular, the record does not report event timing, participant-level overlap, exposure-adjusted rates, or statistical uncertainty for those figures.

More generally, a randomized design can make treatment groups informative to compare, but interpretation depends on the actual results, the analysis methods, and how missing data and multiple outcomes were handled. Those details are not reported in the registry record. The available information supports a description of the design, measures, and posted safety counts—not a conclusion about efficacy, clinical importance, or the balance of benefits and harms.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized, placebo-controlled investigation of sodium oxybate for treatment-resistant RBD. The registry describes it as the first clinical trial using sodium oxybate for RBD. Its primary measure is based on patient logs of dream-enactment episodes, while secondary measures include clinician ratings, sleepiness, video-polysomnography, and actigraphy. These methods represent different ways of capturing symptoms and sleep-related activity; they are not interchangeable outcomes.

The record also illustrates why an outcome definition alone is not enough for statistical interpretation. It specifies a median and inter-quartile range and states that participants need data at both time points to enter the primary analysis. Yet it does not report the outcome summaries, a between-arm contrast, or uncertainty around that contrast. Nor does it identify a single primary comparison from the stated categories or time points. Readers can understand the intended measurement, but cannot assess its observed effect from this record.

The separation between design information and result information is important. Randomization and masking describe features intended to strengthen a comparison; neither reveals the result. Likewise, the listed adverse-event counts are useful descriptive information but do not substitute for a comparative analysis with context and uncertainty.

Finally, the registry’s planning assumptions should not be confused with observed power or with evidence of an effect. The record does not report the trial’s sample-size justification or full statistical plan. This case therefore highlights the value of complete reporting: estimates, uncertainty, analysis populations, missing-data methods, and multiplicity handling are needed to move from a trial description to a 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 registry record does not report numerical results for the primary endpoint, despite listing the study as completed. It also does not reduce the endpoint’s multiple categories or time points to one comparison. Without outcome summaries, a treatment contrast, or an uncertainty interval, the primary question cannot be evaluated from the record.

Further details needed to assess design and analysis are not reported in the registry record. These include eligibility criteria, baseline characteristics, the randomization procedure, allocation concealment, masking procedures, dosing, adherence, and the statistical analysis plan. The record does not explain the analysis model or whether the primary analysis adjusted for baseline values or other covariates.

The primary analysis population is described as participants with data at each time point, but the number with complete data, reasons for missingness, and methods for handling missing observations are not reported. The record also does not describe interim analyses, multiplicity control, or whether analysis populations beyond the stated population were used. The listed planning assumptions do not establish the trial’s own sample-size justification.

For safety, the registry gives affected-participant counts and a list of serious-event terms, but not event timing, participant-level overlap, duration, attribution, or exposure-adjusted rates. The listed terms are not assigned to an arm. These limitations mean the posted information supports only a bounded description of the design, endpoint, and adverse-event counts, rather than a full efficacy or safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate — NCT04006925.
• Registry record last updated 2023-05-10; status last verified 2023-04.
• Results first posted 2023-05-10.
• 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

The registry record describes NCT04006925, a completed Phase 4, randomized, quadruple-masked, parallel-group study sponsored by Stanford University. It lists enrollment as 24 and compares sodium oxybate with placebo in treatment-resistant REM sleep behavior disorder. The recorded study start date is 2019-09-10, and the primary completion date is 2022-02-01.

The primary outcome is the number of RBD episodes in one month, recorded in a patient log and summarized using the median and inter-quartile range. Measurements were planned at baseline and during the last month of treatment, which lasted up to 12 weeks. The primary analysis population is described as participants with data at each time point.

The registry record does not report numerical primary or secondary outcome results, a treatment-effect estimate, or its uncertainty. It posts serious and other adverse-event counts by arm and lists several serious-event terms. Details of the statistical analysis plan, missing-data handling, and multiplicity methods are not reported in the registry record.