This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Oral Low-Dose Naltrexone for Lichen Planopilaris and Frontal Fibrosing Alopecia (NCT04409041), a na phase 2 study. The primary outcome is Change in Patient-Reported Itch.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04409041 |
| Phase | Phase 2 |
| Condition | Lichen Planopilaris, Frontal Fibrosing Alopecia |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 43 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Participants had lichen planopilaris or frontal fibrosing alopecia. The registry record reports enrollment of 43 participants. The primary endpoint population is described as the per protocol group, but its size and the criteria for inclusion in that group are not reported in the registry record.
Intervention
Participants were prescribed low-dose naltrexone at 3mg orally daily. The study description says participants would continue their other medications for these conditions. The study was open-label, so participants and study personnel were not masked to the intervention.
Comparator
There was no separate control group. This was a single-group study with no randomized comparison. Consequently, the registry record does not offer a like-for-like untreated or alternative-treatment group against which to compare changes over time.
Primary question
The primary endpoint was change in patient-reported itch at 12 months, measured on a 0-10 scale on which lower scores are better. The registry record identifies the endpoint as a mean with a 95% confidence interval, but does not report the observed mean change or its interval. The amount and precision of any observed change therefore cannot be assessed from the registry record.
The study addresses whether patient-reported itch changed during follow-up among participants prescribed low-dose naltrexone. It does not, by design, isolate the effect of the drug from changes that might occur over time for other reasons. Such factors can include the natural course of a condition, ongoing treatments, expectations in an unmasked study, and differences in which participants complete follow-up. These are general considerations for interpreting an uncontrolled open-label study, not findings about what occurred in this study.
The registry describes planned visits at 0, 3, 6 and 12 months. The primary endpoint is specified at 12 months, and the description says a change between two time points is reported then. The exact pair of time points used to calculate the primary change is not stated. The clinical question is therefore identifiable in broad terms, but important details for interpreting the endpoint and the observed result are not reported in the registry record.
3. Trial Design
This was a Phase 2, prospective, open-label study with a single group and no allocation to a control condition. The registry lists 43 participants as enrolled and marks the study completed. Its title identifies lichen planopilaris and frontal fibrosing alopecia as the conditions under study. Washington University School of Medicine is listed as the sponsor.
All participants were prescribed low-dose naltrexone at 3mg orally daily. The study description says participants would continue their other medications for these conditions. The planned visits were at 0, 3, 6 and 12 months. The primary endpoint is a patient-reported itch measure at 12 months. The registry identifies the primary analysis population as the per protocol group, but does not report how that group was defined or how many participants it contained.
The study began on 2019-09-01, and the primary completion date is 2020-12-31. The status is completed. These dates describe the record's study timeline; they do not establish how many participants attended each visit or contributed to the primary analysis. Those counts are not reported in the registry record.
Open-label means that masking was absent. A single-group design can describe outcomes observed among participants receiving the intervention, but it cannot provide a direct between-group estimate of treatment effect. Without a concurrent control group, change over time may reflect multiple influences, including the intervention, ongoing medications, natural variation, or measurement and expectation effects. These are general design considerations; the registry record does not determine which influences affected participants.
The registry lists four outcome measures and zero analyses. It does not report the statistical analysis plan, a sample-size justification, or details of interim analyses. The design record should therefore be read as a description of the study structure and registered endpoint, not as a complete account of how all data were handled or analyzed.
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
| Stage | Treatment Group (Low-dose Naltrexone) |
|---|---|
| STARTED | 43 |
| COMPLETED | 26 |
| NOT COMPLETED | 17 |
Analysis population for the primary outcome, as defined in the registry: Per protocol group
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: 43 patients enrolled.
| Characteristic | Unit | Treatment Group (Low-dose Naltrexone) |
|---|---|---|
| Participants analysed | 43 | |
| Age, Continuous | years | 65 (SD 10.7) |
| Sex: Female, Male: Female | Participants | 41 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 43 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 41 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Patient-Reported Itch, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in patient-reported itch, assessed on a 0-10 scale. The registry states that lower scores represent a better outcome and describes the endpoint as a change between two time points reported at 12 months. It does not specify the exact pair of time points in the endpoint description. The primary analysis population is the per protocol group.
Itch is a symptom reported by participants rather than an objective measurement of scalp inflammation or hair loss. A patient-reported scale can capture an aspect of the experience that matters directly to the person living with a condition. As a general measurement principle, a numerical scale can make symptom reports easier to summarize and compare across follow-up, while still depending on how participants understand and use the scale.
The registry specifies a mean and a 95% confidence interval for this continuous endpoint. The mean describes the average reported change in the analysis population. A confidence interval conveys uncertainty around an estimate: in general, narrower intervals indicate greater precision, while wider intervals indicate less precision. The actual mean change and confidence interval are not reported in the registry record, so neither the direction nor the precision of the observed primary result can be evaluated.
The subtraction convention for the change score is also not stated. Although lower itch scores are described as better, the sign of a change depends on which time point is subtracted from which. The scale's direction is clear, but the direction of a numerical change cannot be interpreted without that calculation detail and the result itself.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary endpoint and its summary measure, but does not report the primary endpoint estimate. No observed mean change or 95% confidence interval is available in the registry record. As a result, it is not possible to describe whether the recorded itch scores increased or decreased on average, how large the mean change was, or how precisely it was estimated. This absence of a result is distinct from a result showing no change.
Even if a mean change and confidence interval were available, an uncontrolled open-label study would support a descriptive interpretation of change among participants in the analyzed group, not a direct comparison with an untreated group. Changes between visits can arise for more than one reason. General possibilities include natural symptom fluctuation, continued medications, participant expectations, measurement variability, and selective follow-up. Without a control group, the study cannot separate these influences from the effect of the intervention.
The primary analysis population is called the per protocol group. This label generally refers to participants who meet specified protocol-related requirements, but the particular requirements and the number included are not reported in the registry record. If participants with incomplete follow-up or deviations differ from those analyzed, the per protocol estimate may not describe all 43 enrolled participants. Whether that concern applies cannot be established from the registry record.
Enrollment of 43 describes the number entered for the study, not necessarily the number contributing data to the 12-month endpoint. The endpoint denominator, visit completion, and handling of missing itch assessments are not reported in the registry record. This matters because precision depends partly on how much outcome information is available, and the analysis population may be smaller than enrollment.
The record lists four outcome measures and zero analyses. It does not report whether the primary endpoint was tested against a null hypothesis, whether any secondary outcomes were analyzed, or how multiplicity was addressed. The absence of a posted analysis means there is no reported p-value or inferential conclusion to interpret. It should not be taken as evidence for or against a treatment effect.
Safety information is reported separately: the treatment group lists 34 participants at risk for serious adverse events and 2 affected, and 34 at risk for other adverse events and 10 affected. The record also lists 0 deaths and identifies breast cancer at 5.9% among the top serious terms. These figures describe recorded events in the posted safety categories. They do not establish whether events were caused by the intervention, and the registry record does not provide enough detail to make such an attribution.
Overall, the record describes the study's setting, treatment, and intended symptom endpoint, but it does not provide the primary outcome result. Statistical interpretation must therefore remain limited to design features and the safety counts that are posted. No conclusion about the amount of itch change or its cause can be drawn from the missing endpoint estimate.
9. Statistical Methods Explained
The registry characterizes the primary endpoint as a continuous measure summarized by a mean and a 95% confidence interval. The mean is an average across the participants included in the analysis. It is useful for describing the central tendency of a quantitative outcome, but by itself does not show how individual participants' scores varied. The registry record does not report a measure of individual variability for the primary endpoint.
A confidence interval is a statistical summary of uncertainty around an estimate. In general, an interval describes a range of values compatible with the data and the method used to calculate it. Its width is informative about precision: a wider interval indicates more uncertainty about the estimated mean than a narrower interval. A confidence interval is not a guarantee that the true value lies within its particular bounds. Here, the record specifies a 95% confidence interval but does not post its endpoints, so its width and the precision of the mean change cannot be assessed.
What does the single-group design allow?
In a single-group study, outcomes can be described before and after participants receive an intervention, but there is no concurrent comparison group to show what might have happened without it. General statistical interpretation distinguishes a within-group change from a between-group contrast. A within-group change is an observation over time; it does not by itself identify the cause of that change. This distinction is central to interpreting this open-label study.
The absence of masking also matters in general. Participants who know they are receiving an intervention may report symptoms differently, and study personnel who know the treatment assignment may influence measurement or follow-up in subtle ways. These are possible sources of bias in open-label research, not claims that bias occurred in this study. The registry records masking as none.
How should the itch scale be read?
The itch instrument is described as a 0-10 scale, with lower scores indicating a better outcome. A numerical scale creates a consistent format for symptom reporting, but its interpretation depends on the scale instructions and the way change is calculated. The record says a change between two time points is reported at 12 months, but does not identify the specific pair or state the subtraction order. Therefore, the scale's favorable direction is clear, while the sign of a change score is not interpretable without those details.
The registry reports a mean change rather than a proportion of participants who improved. A mean can summarize the overall direction and average amount of change, but it can conceal varied individual experiences: some participants could have changes in one direction and others in the opposite direction. Individual-level distributions and responder definitions are not reported in the registry record.
What can be inferred from the analysis population?
The primary endpoint is associated with the per protocol group. In general, a per protocol analysis focuses on participants who satisfy the study's protocol requirements, whereas an analysis of all enrolled participants would include a broader group. The exact definition of protocol adherence, the size of the per protocol group, and whether any alternative analysis was conducted are not reported. The 43 enrolled participants should not automatically be treated as the denominator for the primary endpoint.
Missing observations can affect both the estimate and its uncertainty. If participants with missing follow-up differ from those with observed follow-up, an analysis of available outcomes may represent a selected group. General methods for missing data include explicit assumptions and procedures for handling incomplete measurements, but the registry does not report which approach, if any, was used. The amount and pattern of missing primary endpoint data are also not reported.
What do the planning assumptions mean?
The registry describes sample-size planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not a description of the study's actual design: the trial itself was single-group and did not use equal allocation between two arms. The illustration is not the trial's own design justification, and a calculated sample size is not observed power. The sample-size justification for this study is not reported in the registry record.
More generally, sample-size planning asks how much information might be needed for a specified statistical objective under stated assumptions. Such illustrations depend on the effect size chosen, variability, and analysis method. They do not establish that the study achieved a particular level of power, nor do they replace reporting the observed estimate and its uncertainty. The registry does not report an observed primary endpoint estimate from which readers could judge how the trial's actual information compares with its planning illustration.
The analysis method used to construct the primary confidence interval, any model adjustments, and any hypothesis-testing procedure are not reported in the registry record. No specific inferential method beyond the summary type should therefore be attributed to this study. General concepts such as interval estimation explain how such statistics are commonly interpreted, but they do not identify the analysis actually performed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, but does not report the results for the primary itch endpoint or the other outcomes. It also lists zero analyses. A count of outcome measures does not establish how many comparisons were actually tested, which outcomes were treated as primary or secondary in analysis, or whether any results were selected for reporting.
Multiplicity arises when several outcomes or statistical comparisons are examined. As a general matter, repeated testing can increase the chance of finding at least one apparently unusual result by chance. Analysts may address this through prespecified priorities or statistical adjustments, but the multiplicity approach is not reported in the registry record. The record also does not report a detailed statistical analysis plan or interim analyses.
The primary endpoint population is described as per protocol. Its definition and size are not reported. The registry does not state how missing itch assessments were handled, whether participants with incomplete follow-up were excluded, or whether an alternative analysis population was examined. The numbers attending each planned visit and the primary endpoint denominator are not reported in the registry record.
These omissions limit assessment of how the analysis population was formed and whether missing observations could have influenced the reported estimate. Because the primary estimate itself is not posted, its robustness to different assumptions or analytic choices cannot be evaluated. The record also does not report a sample-size justification for the study. The planning illustrations described in the record are not a substitute for that justification and do not establish observed power.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment Group (Low-dose Naltrexone) | 2 | 34 | 5.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Group (Low-dose Naltrexone) | 0 of 34 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Group (Low-dose Naltrexone) | 10 of 34 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment Group (Low-dose Naltrexone) |
|---|---|---|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment Group (Low-dose Naltrexone) |
|---|---|---|
| vivid dreams | Nervous system disorders | 7 of 34 |
| headache | Nervous system disorders | 3 of 34 |
Serious events with the highest arm-level rate: breast cancer (5.9%).
The registry reports 34 participants at risk for serious adverse events, with 2 affected, and 34 at risk for other adverse events, with 10 affected. It lists 0 deaths. The top serious term is breast cancer, reported at 5.9%. These figures are counts and a percentage in the posted safety record; they should be read within the categories and denominators stated there.
Serious adverse events and other adverse events are separate reporting categories, and the record does not provide definitions or detailed event narratives in the available information. The affected counts should not be added together or treated as a count of unique participants, because overlap between categories is not reported. The difference between enrollment and the safety denominator is also not explained in the registry record.
An event occurring during a study does not, by itself, show that the intervention caused it. The registry record does not report an attribution assessment for these events. The listed breast cancer term likewise cannot be interpreted as caused by treatment on the basis of the posted information. The safety figures describe what was recorded, rather than establishing causation or providing a comparison with a control group.
12. What the Result Does, and Does Not, Mean
The record establishes that a prospective, open-label, single-group study of low-dose naltrexone was completed in participants with lichen planopilaris or frontal fibrosing alopecia. It identifies a patient-reported itch change at 12 months as the primary endpoint and states that lower scores on the 0-10 scale are better. It also reports safety counts for the treatment group. These are descriptions of the registered study and posted data, not evidence of a causal treatment effect.
The primary outcome result is not reported in the registry record. There is no reported mean change or 95% confidence interval to indicate the direction, size, or precision of the average itch change. The absence of that result does not mean that the endpoint showed no change, and it does not establish that the intervention did or did not affect symptoms.
Even a posted change in an uncontrolled group would need cautious interpretation. Without a concurrent comparator, the observed change could not be separated from general influences such as ongoing medication, natural variation, expectations, or selection into follow-up. These are standard limitations of an uncontrolled open-label design, not claims about the actual source of any change in this study.
The reported safety categories show 2 affected among 34 at risk for serious adverse events, 10 affected among 34 at risk for other adverse events, and 0 deaths. Breast cancer is listed as a top serious term at 5.9%. The registry record does not establish that any event was caused by the intervention, and it does not give a comparison group for evaluating event rates.
Accordingly, the record supports a description of study design, intended symptom measurement, enrollment, and posted safety figures. It does not support a conclusion about the intervention's effect on itch or the cause of the adverse events. The endpoint estimate, analysis details, and follow-up accounting needed for a fuller statistical assessment are not reported in the registry record.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the difference between measuring change and estimating a comparative effect. A single-group study can collect repeated symptom reports and describe how scores change during follow-up. Without a control group, however, it cannot distinguish an intervention-related change from other influences on symptoms over time. That distinction is important when interpreting evidence from prospective studies.
The registered endpoint is patient-reported itch, a symptom that may not be represented by other clinical measures. Using a defined scale can make the symptom measurable and can support a summary such as a mean change with a confidence interval. But a scale's usefulness also depends on clear reporting of the time points, scoring direction, change convention, and analysis population. The registry record identifies the scale direction and summary type, while leaving some of these details unspecified.
The gap between enrollment and the reported safety denominator, and the lack of a reported primary endpoint denominator, also highlight why participant flow matters. Enrollment alone does not show how much outcome information was available at the final assessment. Reporting follow-up, missingness, and analysis populations helps readers judge how well an estimate represents the enrolled group.
Finally, the record shows why an endpoint's registration and its result are both needed for interpretation. Naming a primary outcome does not reveal its observed value. Without the mean change and confidence interval, readers cannot assess the direction or precision of the primary result. The record therefore provides a useful design description but an incomplete statistical account of the main clinical question.
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 interpreting this specific study is that the registry record does not report the primary itch estimate or its 95% confidence interval. The outcome's direction, average magnitude, and precision are consequently unavailable. The description also does not specify the exact two time points used for the change calculation or its subtraction order.
The single-group, open-label design has no concurrent control and no masking. As a result, changes in patient-reported symptoms cannot be attributed to the intervention alone. This design limitation is especially relevant to an outcome based on participant reports, though the registry record does not establish that reporting bias occurred.
The primary population is identified as per protocol, but the definition and size of that population are not reported. The registry record also does not provide the primary endpoint denominator, visit completion counts, missing-data procedures, or an account of participants who did not complete follow-up. Enrollment of 43 therefore does not establish how many participants contributed to the primary result.
The record lists four outcome measures and zero analyses, but does not report a detailed statistical plan, multiplicity handling, interim analyses, or a sample-size justification. Without these details, it is difficult to assess whether the analysis followed prespecified methods or how the outcomes were prioritized. No conclusion about the study's actual analysis procedure should be inferred from the summary measure alone.
The safety record provides event counts and a serious-event term, but does not report event-level context, attribution, or a comparison group. The relationship between the enrolled population and the safety denominator is not explained. These limitations restrict interpretation of both the primary endpoint and the safety information to the details explicitly recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Oral Low-Dose Naltrexone for Lichen Planopilaris and Frontal Fibrosing Alopecia — NCT04409041.
- Registry record last updated 2021-12-30; status last verified 2021-11.
- Results first posted 2021-12-30.
- 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.
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18. Record Summary
The registry record describes a completed Phase 2, prospective, open-label, single-group study sponsored by Washington University School of Medicine. It enrolled 43 participants with lichen planopilaris or frontal fibrosing alopecia. Participants were prescribed low-dose naltrexone at 3mg orally daily, with other medications continued as described in the study summary. Planned visits were at 0, 3, 6 and 12 months.
The primary endpoint was change in patient-reported itch at 12 months on a 0-10 scale, where lower scores are better. It was summarized as a mean with a 95% confidence interval in the per protocol group. The primary endpoint result, analysis population size, and missing-data approach are not reported in the registry record.
Safety figures list 2 affected among 34 at risk for serious adverse events, 10 affected among 34 at risk for other adverse events, and 0 deaths. Breast cancer is listed among the top serious terms at 5.9%. The record does not establish that any event was caused by the intervention. No randomized comparison was conducted.