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 Melatonin and Osteogenic Loading on Osteopenia (NCT04233112), a randomized early/phase 1 study. The primary outcome is Bone Mineral Density Femoral Neck.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04233112 |
| Phase | EARLY/Phase 1 |
| Condition | Osteopenia |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Quadruple |
| Enrollment | 27 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Duquesne University |
| Results posted | Yes |
2. Clinical Question
Population
People with osteopenia were enrolled in a study of bone health. The registry record reports enrollment of 27. For the primary outcome, participants who completed the trial were included, except for one participant in the melatonin/osteogenic loading group whose DXA measurement could not be obtained because of hip implants.
Intervention
The study combined melatonin capsules or placebo capsules with osteogenic loading or mock loading. The melatonin intervention is listed as Melatonin 5 mg. The placebo is described as plant fiber. Osteogenic loading and mock osteogenic loading are listed as device interventions.
Comparator
The four listed combinations were Placebo/Mock, Melatonin/Mock, Placebo/Osteogenic Loading, and Melatonin/Osteogenic Loading. This arrangement allows the record to show results for combinations of the two interventions. However, posted values are not estimable for a two-arm comparison of the continuous primary endpoint.
Primary question
The primary outcome concerns change in femoral-neck bone mineral density T-score over 0-12 months. The underlying question is whether the posted group-level changes in this measure differ across the melatonin and loading combinations. The registry record does not report an inferential analysis answering that comparative question.
The study description frames the research as assessing melatonin and/or osteogenic loading in an osteopenic population. The primary endpoint is a bone-density measure rather than a clinical event. Its interpretation depends on both the direction of change and the uncertainty around the group estimates. The record posts means and standard deviations for the individual combinations, but does not post confidence intervals, p-values, or a two-arm comparison for the primary endpoint. The numerical results therefore describe observed group summaries; they do not establish whether differences between combinations are distinguishable from sampling variability.
3. Trial Design
The registry record identifies the study as randomized and quadruple masked, with Duquesne University as sponsor. It lists an early-phase 1 designation and a single-group model. At the same time, the intervention descriptions and posted results identify four combinations of melatonin or placebo with osteogenic or mock loading. The registry record does not explain how the single-group model classification relates to these four combinations.
Enrollment is listed as 27. The study is marked completed. Its listed start date is 2020-07-02, and its primary completion date is 2024-08-08. These registry dates describe the record's study timeline, but do not by themselves establish when each participant received an intervention or how long each participant was followed.
The four combinations are Placebo/Mock, Melatonin/Mock, Placebo/Osteogenic Loading, and Melatonin/Osteogenic Loading. The listed placebo capsules contain plant fiber, and the melatonin intervention is 5 mg. The registry record lists osteogenic loading and mock loading as device interventions. The details of the loading procedure, capsule schedule, and masking procedures are not reported in the registry record.
The primary outcome is femoral-neck bone mineral density measured by DXA, expressed as a T-score. The timeframe is 0-12 months, and change is defined as the 12-month T-score minus the baseline T-score. Posted outcome counts vary across combinations, and the record notes that one participant in the melatonin/loading group could not have a DXA measurement because of hip implants. A detailed participant flow, reasons for non-completion, and an account of allocation procedures are not reported in the registry record.
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: Participants were excluded and not randomized if osteoporosis was detected based on our DXA screening.
Overall Study
| Stage | Placebo/Mock | Melatonin/Mock | Placebo/Osteogenic Loading | Melatonin/Osteogenic Loading |
|---|---|---|---|---|
| STARTED | 6 | 6 | 8 | 7 |
| COMPLETED | 5 | 4 | 6 | 4 |
| NOT COMPLETED | 1 | 2 | 2 | 3 |
Reasons for not completing this period:
| Reason | Placebo/Mock | Melatonin/Mock | Placebo/Osteogenic Loading | Melatonin/Osteogenic Loading |
|---|---|---|---|---|
| Reasons unrelated to treatment | 1 | 1 | 1 | 2 |
| Withdrawal by Subject | 0 | 0 | 1 | 1 |
| Lost to Follow-up | 0 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who completed the trial were included except for one participant in the melatonin/loading group who could not have their DXA measured due to hip implants.
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: Baseline measures are reported for 19 participants in the baseline analysis population, rather than all 27 randomized participants. The remaining 8 participants were not included due to participant withdrawal.
| Characteristic | Unit | Placebo/Mock | Melatonin/Mock | Placebo/Osteogenic Loading | Melatonin/Osteogenic Loading | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 5 | 4 | 6 | 4 | 19 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 0 | 0 | 4 | 5 |
| Age, Categorical: >=65 years | Participants | 4 | 4 | 6 | 0 | 14 |
| Sex: Female, Male: Female | Participants | 5 | 4 | 6 | 4 | 19 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 5 | 3 | 6 | 4 | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Bone Mineral Density Femoral Neck, measured over 0-12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | T-score |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in femoral-neck bone mineral density T-score over 0-12 months. DXA measures bone mineral density, and the T-score expresses a participant's BMD in relation to a healthy young-adult reference population. A T-score of 0 represents that reference mean. A one-unit difference corresponds to one standard deviation above or below the reference mean. Higher, or less negative, values indicate greater BMD.
The registry record describes clinical categories as greater than -1.0 for normal, -1.0 to -2.5 for osteopenia, and less than or equal to -2.5 for osteoporosis. A mean femoral-neck T-score of -1.7 is described in the record as below the reference mean and within the osteopenic range. The primary result, however, is change from baseline, not simply the classification of a mean value at one time point.
Change is calculated by subtracting the baseline T-score from the 12-month T-score. A positive change indicates a higher follow-up T-score than baseline; a negative change indicates a lower follow-up T-score. This is a continuous endpoint, so group means describe average change and standard deviations describe variation among participants. In general, continuous measures can retain more information about the range of observed values than a binary classification, but the meaning of a group average does not establish what happened to every participant.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome values are mean changes in femoral-neck T-score. Placebo/Mock has a mean change of 0.04 with a standard deviation of 0.1 among 5.0 participants. Melatonin/Mock has a mean change of -0.1 with a standard deviation of 0.1 among 4.0 participants. Placebo/Osteogenic Loading has a mean change of -0.1 with a standard deviation of 0.2 among 6.0 participants. Melatonin/Osteogenic Loading has a mean change of 0.0 with a standard deviation of 0.0 among 3.0 participants.
These figures are descriptive summaries for the listed combinations. They indicate the direction and observed spread of the group-level changes, but they are not estimates of treatment contrasts. The registry record explicitly indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Consequently, no comparative effect estimate, confidence interval, or inferential p-value is posted for the primary outcome. It is not possible to determine from these summaries whether observed group differences are compatible with random variation or reflect a reproducible difference.
The standard deviations are also descriptive. They summarize how dispersed the observed individual changes were around each group mean; they are not standard errors or confidence intervals. In particular, a reported standard deviation of 0.0 for the Melatonin/Osteogenic Loading group reflects the posted summary for 3.0 participants, not proof that the outcome is identical for all people in a broader population. With few observations, group estimates can be sensitive to the values of individual participants.
The registry record states that one participant in the melatonin/loading group could not have a DXA measurement because of hip implants. The primary-outcome population excludes that participant. The outcome count for that group is 3.0, while the adverse-event record lists 4 participants at risk in the corresponding combination. These are different outcome contexts and denominators. The record does not provide a full explanation of participant flow or missing outcome data beyond the DXA limitation.
In general, a confidence interval would show a range of values compatible with the data and the chosen statistical method, conveying precision as well as direction. No such interval is posted for the primary comparison. The result should therefore be read as small-sample descriptive evidence about observed changes, not as a tested conclusion about comparative effects. The record contains no reported primary-outcome analysis that resolves the comparative question.
9. Statistical Methods Explained
The primary measure is continuous, and the posted summaries use a mean and standard deviation. In general, a mean is the arithmetic average of observed values. It gives a compact description of the group's central value, but may not represent every participant's experience. The standard deviation describes the dispersion of individual observations around that mean. It is not a measure of uncertainty in the mean itself.
What does change in T-score represent?
The registry defines change as the 12-month T-score minus the baseline T-score. In general, subtracting the starting value from a later value expresses direction of change on the same measurement scale. A positive value means the later score is higher than baseline, while a negative value means it is lower. The posted means therefore describe average change in femoral-neck T-score, not the mean T-score at the end of follow-up. The record does not post a baseline-to-follow-up analysis with adjusted estimates.
Why distinguish a mean from its uncertainty?
A mean describes the center of the observed values. A confidence interval, in general, describes uncertainty around an estimated quantity under a specified method and assumptions. It helps readers assess how precisely the quantity has been estimated. A standard deviation cannot be substituted for a confidence interval: the two describe different features of the data. The registry record reports standard deviations for the individual combinations but no confidence interval for a comparative effect. It also reports no two-arm analysis for this continuous endpoint.
What can group summaries establish?
Group-level means can describe the observed results in each listed combination. They do not, by themselves, test whether the combinations differ. A comparative analysis would need to define the contrast of interest and estimate its uncertainty. The registry record identifies a control group and four combinations, but reports values as not estimable for a two-arm comparison of the continuous endpoint. The basis for the unavailable comparison is not detailed beyond that note. No adjusted or unadjusted comparative estimate is posted.
How should the group sizes be read?
The outcome summaries are based on 5.0, 4.0, 6.0, and 3.0 participants in the listed combinations. In general, estimates from small groups are less stable because each participant's result can have appreciable influence on the group summary. A zero standard deviation in a small observed group is a description of those observed values, not a statement that the population has no variation. The registry record does not post confidence intervals that would quantify uncertainty for these individual means.
What do sample-size calculations mean?
In general, a planning calculation asks how many participants would be needed under specified assumptions to detect a chosen effect with a target probability of statistical detection. Such figures are planning illustrations, not observed power and not evidence that a trial did or did not find an effect. The registry record describes a planning approach using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. It does not report a sample-size justification for the original trial design. Because the continuous two-arm comparison is marked not estimable, no comparative effect is available in the registry record to support a meaningful interpretation of a planning illustration for that contrast.
In general, analysis choices also depend on the study design, the definition of the target comparison, assumptions about the outcome distribution, and the handling of missing observations. The registry record does not report a detailed statistical analysis plan, the model used for the primary outcome, or an adjustment strategy. It also does not report whether any interim analyses were planned or conducted. These omissions limit the ability to evaluate how the posted summaries relate to any prespecified analysis.
For a continuous measure, a normal approximation may be used in some analyses, but its suitability depends on the data and the analysis design. The registry record does not provide participant-level values or distributional diagnostics. General concerns about small samples and distributional assumptions should not be mistaken for evidence that a particular assumption failed in this study. The posted results support descriptive reading of group means and standard deviations; stronger inferential claims require analyses that are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study includes four combinations of two intervention components and reports three outcome measures. The registry record does not identify a multiplicity adjustment, a hierarchy of outcomes, or a plan for prioritizing among multiple comparisons. It does not report the number of planned primary comparisons or how any secondary outcomes were to be handled. The registry record reports no secondary outcomes posted.
In general, when several outcomes or contrasts are tested, the chance of at least one apparently unusual result can increase if each is evaluated separately. A prespecified testing strategy or multiplicity adjustment can help address that issue. Since no comparative primary-outcome analysis is posted, there are no posted comparison p-values to interpret in light of multiplicity. The registry record does not report whether analyses were conducted but omitted, or whether comparisons were not estimable under the analysis approach.
The primary outcome population excludes one participant in the melatonin/loading group whose DXA measurement could not be obtained because of hip implants. The record does not describe imputation, a sensitivity analysis, or another method for handling that missing measurement. It does not report whether other outcome data were missing or how incomplete follow-up was treated. The posted group sizes describe the participants included in the endpoint summaries, but a full account of analysis populations is not reported in the registry record.
In general, a complete analysis-population description clarifies which randomized participants were included, how deviations from assigned treatment were handled, and whether the analysis followed assignment or actual exposure. The registry record does not report those details. The noted exclusion is important context for the outcome count, but it is not enough to establish the broader missing-data strategy or analysis population.
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 |
|---|---|---|---|
| Placebo/Mock Loading | 0 | 5 | 0.0% |
| Melatonin/Mock Loading | 0 | 4 | 0.0% |
| Placebo/Osteogenic Loading | 0 | 6 | 0.0% |
| Melatonin/Osteogenic Loading | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo/Mock Loading | 0 of 5 |
| Melatonin/Mock Loading | 0 of 4 |
| Placebo/Osteogenic Loading | 0 of 6 |
| Melatonin/Osteogenic Loading | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo/Mock Loading | 0 of 5 |
| Melatonin/Mock Loading | 0 of 4 |
| Placebo/Osteogenic Loading | 0 of 6 |
| Melatonin/Osteogenic Loading | 0 of 4 |
The adverse-event record lists zero serious adverse events and zero other adverse events in each of the four groups. The corresponding numbers at risk are 5 in Placebo/Mock Loading, 4 in Melatonin/Mock Loading, 6 in Placebo/Osteogenic Loading, and 4 in Melatonin/Osteogenic Loading. No deaths are listed in any group. No serious-event terms are listed.
These counts describe what was recorded among the listed participants at risk. They should not be read as proof that no adverse events could occur or as a comparison establishing equivalent safety between groups. In general, a zero count in a small group still leaves uncertainty about the range of possible event frequencies in a larger population. The registry record does not report confidence intervals or a formal statistical comparison for adverse events.
The outcome denominator for Melatonin/Osteogenic Loading is 3.0 participants, whereas the safety record lists 4 participants at risk in that group. The record does not explain this difference. Safety counts and outcome counts can have different definitions or follow-up requirements, but the reason for the difference is not reported in the registry record. The serious-event figures should therefore be interpreted as recorded counts, with the denominators and reporting details in mind, rather than as a comprehensive estimate of safety risk.
12. What the Result Does, and Does Not, Mean
The results establish that the registry record contains descriptive femoral-neck T-score changes for four intervention combinations and recorded adverse-event counts. The endpoint is a change from baseline over 0-12 months. The observed group means range from -0.1 to 0.04, with the posted standard deviations ranging from 0.0 to 0.2. The counts of participants in the outcome summaries are small, and one DXA measurement was unavailable because of hip implants.
The results do not establish whether melatonin, osteogenic loading, or their combination changed bone density relative to placebo or mock loading. The record does not provide an estimable two-arm comparison, confidence interval, or p-value for the continuous primary endpoint. Group means alone cannot answer whether the observed differences are statistically distinguishable from chance variation. The registry record also does not report a detailed analysis plan that would clarify the intended comparative model.
In general, statistical uncertainty is not the same as absence of an effect. When a comparison is not reported, a reader cannot use the missing test or interval to determine whether the data are compatible with a range of comparative effects. Likewise, a small mean change or a standard deviation of 0.0 among a few participants should not be treated as evidence that the same pattern would occur in a larger group.
The record's zero adverse-event counts are similarly descriptive. They do not demonstrate that the interventions have no risks or that risks are equal across groups. Taken together, the posted information allows a limited description of the observed summaries, but not a conclusive comparative assessment of the interventions. The unreported analysis details, small outcome groups, and missing DXA measurement further constrain interpretation.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it combines two intervention components and presents four combinations, while the primary outcome is continuous and the posted comparative analysis is not estimable. The distinction between reporting group summaries and reporting a treatment contrast is central. Means and standard deviations describe observed data, but they do not substitute for an estimate of the difference between groups and its uncertainty.
The registry record also illustrates why denominators need to be read in context. The primary outcome excludes a participant whose DXA measurement was unavailable, while the corresponding safety count includes 4 participants at risk. Without a participant-flow account or a missing-data description, readers cannot assume that the same population contributes to every result.
In general, factorial or multi-component intervention designs can raise questions about separate component effects and whether components interact. The four combinations make those questions relevant, but the registry record does not report analyses that estimate such effects. It is therefore important not to infer a melatonin effect, a loading effect, or an interaction from separate descriptive means.
The study also highlights the difference between a planning calculation and evidence from observed data. Planning illustrations rely on assumptions about a target effect and analysis, while the trial's posted summaries remain descriptive. Because a comparative effect is not reported, the record does not support a comparison-based conclusion from the primary endpoint. Transparent reporting of the analysis plan, population definitions, missing-data handling, and comparative estimates would be needed to assess the intended statistical question more fully.
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 the primary outcome is the absence of an estimable two-arm comparison. Although means and standard deviations are posted for four combinations, the registry record does not report comparative estimates, confidence intervals, or p-values. This prevents a direct assessment of the size and precision of differences between combinations.
The outcome groups are small: the posted summaries include 5.0, 4.0, 6.0, and 3.0 participants. Such group summaries can be sensitive to individual observations. One participant in the melatonin/loading group could not have a DXA measurement because of hip implants and is excluded from the primary-outcome population. The record does not report a sensitivity analysis or explain how the missing measurement was handled beyond excluding that participant.
Design reporting also leaves questions unresolved. The record labels the study randomized and quadruple masked, but lists a single-group model alongside four intervention combinations. It does not explain this classification or report allocation procedures, masking details, treatment adherence, or participant flow. A detailed statistical analysis plan, sample-size justification, interim-analysis information, and multiplicity strategy are not reported in the registry record.
The adverse-event counts are zero in all listed groups, but the small denominators and lack of uncertainty estimates limit what those counts can establish. The safety denominator for the melatonin/loading combination differs from the primary-outcome count, and the record does not explain why. These limitations concern what can be concluded from the registry record; they do not establish that a particular analysis or study procedure was inappropriate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Melatonin and Osteogenic Loading on Osteopenia — NCT04233112.
- Registry record last updated 2026-10-22; status last verified 2026-04.
- Results first posted 2026-10-22.
- 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
NCT04233112, titled “Melatonin and Osteogenic Loading on Osteopenia,” is listed as completed and sponsored by Duquesne University. The record identifies the study as randomized, quadruple masked, and early phase 1, while also classifying its model as single group. Enrollment is 27.
Four combinations are listed: Placebo/Mock, Melatonin/Mock, Placebo/Osteogenic Loading, and Melatonin/Osteogenic Loading. The primary endpoint is change in femoral-neck BMD T-score from baseline over 0-12 months, measured by DXA. The record posts means and standard deviations for the combinations, but indicates that a two-arm comparison of the continuous outcome is not estimable.
The primary outcome excludes one participant in the melatonin/loading combination whose DXA measurement could not be obtained because of hip implants. The safety record lists zero serious adverse events, zero other adverse events, and zero deaths in every group. Comparative analyses, detailed missing-data methods, and a full statistical analysis plan are not reported in the registry record.