Effect of 1,25-dihydroxyvitamin D3, Treatment on Insulin Secretion and Muscle Strength in Pre-diabetic Persons: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of 1,25-dihydroxyvitamin D3, Treatment on Insulin Secretion and Muscle Strength in Pre-diabetic Persons (NCT04286529), a randomized phase 1 study. The primary outcome is Glucose Levels.

2. Clinical Question

The study was designed to compare calcitriol with placebo in men and premenopausal women with pre-diabetes. The record lists separate calcitriol and placebo arms for each of these groups. It does not describe whether those groups were intended as separate treatment comparisons or how sex and treatment were handled in the analysis.

The primary endpoint description specifies blood glucose after an overnight fast and ingestion of a drink containing 75 grams of glucose. Blood is obtained over a 120 minute period. The stated measurement timeframe is baseline and 8 weeks. However, the registry record reports that data were not collected or analyzed at 8 weeks for the one participant in the Premenopausal Women-Placebo arm.

Although the clinical question concerns a possible change in glucose levels, the registry record does not post the glucose results or an analysis comparing calcitriol with placebo. The question can therefore be described from the trial design, but the treatment contrast cannot be answered from the posted results.

3. Trial Design

The registry record classifies this as a randomized, triple-masked, parallel Phase 1 trial. It lists an enrollment of 17 and a terminated status. The reason for termination is not reported in the registry record. Randomization indicates that assignment was intended to be by chance, while the record does not identify the masked parties or provide further details about the randomization procedure.

The parallel design means that the listed groups received their assigned treatment over the study period rather than being described as crossing from one treatment to another. Four arms are listed: men receiving calcitriol, premenopausal women receiving calcitriol, men receiving placebo, and premenopausal women receiving placebo. For both calcitriol groups, the regimen was a 0.25mcg capsule daily for eight weeks. The placebo descriptions state a 0.25mcg capsule daily for eight weeks.

The registry record gives a study start date of 2020-10-01 and a primary completion date of 2021-05-28. These dates indicate the recorded study timeline, but they do not explain why the trial was terminated or whether its intended enrollment or follow-up changed. Such explanations are not reported in the registry record.

The primary outcome is titled Glucose Levels, with measurements described at baseline and 8 weeks. The record also lists PROMIS 10 Questionnaire as a secondary outcome and states that there are four outcome measures. It does not provide details about the remaining outcome measures in the registry record for this account.

Although the record includes an enrollment total and adverse-event risk counts by arm, it does not report participant flow, numbers completing each assessment, or the analysis population for the primary endpoint. It also gives no statistical analysis plan or outcome comparisons. The trial design is therefore identifiable at a broad level, while key operational and analytical details remain unavailable 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data not collected or analyzed at 8 weeks for the one participant in the Premenopausal Women-Placebo study arm.

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 Glucose Levels, measured over Baseline and 8 weeks.

The primary endpoint is titled Glucose Levels and is recorded as a continuous measure summarized by a mean with standard deviation. The stated unit is mg/dL, and the timeframe is baseline and 8 weeks. The test description says blood is obtained after an overnight fast, followed by a drink containing 75 grams of glucose, with blood obtained over a 120 minute period.

As a general statistical point, glucose measured following a glucose tolerance test can describe how blood glucose changes during the body’s response to an oral glucose challenge. A continuous measure retains more detail than a simple classification into categories, and the mean describes the average level while the standard deviation describes spread among observations. Those summaries are useful for characterizing measurements, but by themselves they do not establish a treatment contrast or show how precisely a contrast has been estimated.

The registry record does not specify which time point or summary of the glucose tolerance test defines the primary endpoint comparison. It says there are several categories or time points, and the outcome was not reduced to one comparison. Nor does the record post the glucose means, standard deviations, or an estimated effect with uncertainty. Data were not collected or analyzed at 8 weeks for the one participant in the Premenopausal Women-Placebo arm. Consequently, the endpoint’s intended measurement process is described, but its numerical findings and treatment comparison are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the design tell us?

The record describes randomized assignment, triple masking, and a parallel model. In general, random assignment is intended to make treatment groups comparable with respect to factors that may affect an outcome. Masking is intended to reduce the influence of knowledge about treatment assignment on behavior, assessment, or analysis. The record does not say which people were masked, how assignment was generated, or how allocation was concealed, so those procedural details are not reported in the registry record.

A parallel design assigns participants to a treatment group and follows them under that assignment. This differs from a crossover design, in which participants would receive more than one treatment in sequence. The record lists four arms based on calcitriol or placebo and men or premenopausal women. It does not specify whether the primary analysis was planned as a pooled treatment comparison, separate sex-group comparisons, or an analysis incorporating both factors.

What do mean and standard deviation describe?

The primary endpoint is continuous, and its stated summary is mean with standard deviation. In general, the mean is the arithmetic average of measurements and the standard deviation describes how dispersed observations are around that average. These summaries describe the distribution of observed data; they are not, by themselves, a statistical test of whether treatment groups differ.

A treatment comparison can be expressed as an estimated difference between groups or as a comparison of changes over time, depending on the analysis plan. A confidence interval describes uncertainty around an estimate under a specified statistical method. It can communicate both the range of effect sizes compatible with the data and the precision of the estimate. The registry record does not report an estimate or confidence interval for glucose levels, nor does it identify the method planned for the repeated measurements.

Why do the time points matter?

The endpoint description includes baseline and 8 weeks, and the glucose tolerance test involves blood collection over a 120 minute period. These are multiple dimensions of measurement: the study visit and the time course following the glucose drink. A statistical analysis needs to define which measurements or summaries answer the primary question. For example, an analysis might focus on a prespecified time point, a change from baseline, or a summary across the test period, but no such approach is reported in the registry record and none should be assumed.

When several outcomes, time points, or comparisons are examined, the chance of finding at least one apparently noteworthy result can increase if each is tested separately without an appropriate strategy. As a general concept, multiplicity methods address the interpretation of multiple statistical tests, for example by adjusting thresholds or defining a hierarchy of outcomes. The record does not report a multiplicity plan or identify a single glucose comparison among its several categories or time points.

What can be learned from the planning illustrations?

The sample-size assumptions describe planning illustrations computed from the observed effect, rather than the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. In general, such an illustration asks how many participants per arm would be needed under those assumptions to target a chosen level of power for a specified effect.

These illustrations are not the observed enrollment, do not show the trial’s planned sample size, and are not observed power. The record does not report a sample-size justification for the actual trial. It also does not report numerical planning results in the registry record, so no numerical sample-size conclusion can be stated. Because the endpoint has not been reduced to a single comparison and no primary outcome analysis is posted, the assumptions behind an illustrative calculation should not be mistaken for the analysis actually conducted.

How should an absent analysis be read?

The record lists zero analyses. This means that no analysis results are posted in the registry record, not that a statistical test found no difference. A missing estimate is not an estimate of zero, and the absence of a p-value does not indicate that a comparison was nonsignificant. The appropriate statistical conclusion is that the outcome effect and its precision cannot be assessed from the posted results.

In general, interpreting a clinical trial also requires knowing the analysis population, handling of missing observations, and any adjustments or modeling choices. The registry record does not provide these details for glucose. The available design and endpoint descriptions are informative about what the study set out to measure, but they cannot replace the outcome data and analysis needed to answer the treatment question.

10. Multiplicity, Missing Data and Analysis Populations

The record describes glucose measurements at baseline and 8 weeks and a glucose tolerance test with blood collection over a 120 minute period. It also states that the primary outcome has several categories or time points and is not reduced to one comparison. The statistical plan for selecting or combining measurements is not reported in the registry record. Nor is a multiplicity strategy reported. As a general matter, multiple outcomes, time points, or comparisons can complicate interpretation because repeated testing can make chance findings more likely; the record does not say how this issue was addressed.

The primary outcome description identifies one participant in the Premenopausal Women-Placebo arm for whom 8-week data were not collected or analyzed. The reason is not reported in the registry record. It does not state whether baseline data were available for that participant, whether the participant contributed to other outcomes, or how the absent 8-week measurement was handled in analysis. The record also does not describe missingness in other arms or time points.

The analysis population is not reported in the registry record. It is therefore not possible to determine whether the primary analysis was based on randomized participants, participants with complete data, or another defined group. The method for handling missing outcomes, any imputation, and any sensitivity analysis are also not reported. No statistical analysis plan or primary outcome analysis is posted. These omissions limit assessment of both multiplicity and the potential influence of incomplete measurements on the result.

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 record lists serious adverse events separately from other adverse events for each of the four arms. It reports zero serious adverse events in each listed group, and zero deaths in each group. For other adverse events, one event is listed in the Men-Calcitriol group; the other listed groups have zero. No serious adverse event terms are listed.

These are event counts, and the record also gives the number at risk for each adverse-event category and arm. They should be read as descriptive information from this trial record rather than as a definitive comparison of safety. In general, a count of zero in a small study does not establish that the true risk is zero. Likewise, an event recorded in one group does not by itself show that treatment caused it. Interpretation would depend on event definitions, follow-up, ascertainment, and comparisons with appropriate uncertainty, which are not reported in the registry record.

The study is listed as terminated, but the record does not state that termination was due to an adverse event or provide a reason. The posted safety figures should not be used to infer a reason for termination or to make a treatment recommendation.

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

The record establishes that a randomized, triple-masked, parallel Phase 1 study was registered to examine calcitriol and placebo in pre-diabetic persons, with glucose levels as the primary outcome. It describes daily capsules for eight weeks, identifies men and premenopausal women in separate arms, and specifies glucose measurements at baseline and 8 weeks after a glucose tolerance test. This information clarifies the study question and measurement context.

What the posted results do not establish is whether glucose levels differed between calcitriol and placebo, how large any difference was, or how precisely it was estimated. The registry record lists no analyses and does not post the primary outcome values or treatment contrasts. That absence must not be interpreted as a null result, as proof of no effect, or as evidence of a particular direction of effect.

The enrollment of 17 and the four-arm structure are important context for the scope of the record, but enrollment alone cannot show whether the study could answer its question. The registry record does not report the trial’s sample-size justification or a planned primary comparison. Planning illustrations based on an observed effect are not a substitute for a prespecified design rationale and are not observed power.

Similarly, the adverse-event counts describe what is listed in the record, but do not provide a definitive assessment of risk. The study’s terminated status is reported without an explanation. No reason for termination should be inferred, and the record does not say whether the status affected the outcome analysis.

The most defensible conclusion is limited to the distinction between design and evidence: the registry describes a trial intended to measure glucose response, but the posted results do not permit estimation or interpretation of a calcitriol-versus-placebo effect on the primary endpoint.

13. Why This Trial Matters Statistically

This trial illustrates why a registered research question and a statistical result are not the same thing. The record contains a clear broad design description: randomized assignment, triple masking, parallel arms, calcitriol and placebo, and glucose as the primary outcome. Yet it lists no analyses and posts no numerical primary outcome comparison. Without an estimate and its uncertainty, the treatment question remains statistically unanswered by the registry record.

The endpoint also raises a common design issue: a measurement can involve more than one visit and multiple readings within a test. Naming an outcome as glucose levels does not, on its own, specify which time point, change, or summary is the primary comparison. The record notes several categories or time points but does not reduce them to a single comparison. This makes a prespecified analytical definition important for interpreting any eventual result.

The four-arm structure further highlights the need for clarity about the intended contrast. Treatment groups are listed separately for men and premenopausal women, but the planned handling of these groups is not reported in the registry record. Without the analysis plan, readers cannot tell whether the intended inference was pooled, group-specific, or based on another approach.

Finally, the listed enrollment, the one missing 8-week observation identified in the primary outcome description, and the terminated status underscore that outcome completeness and trial conduct matter to interpretation. The record does not provide enough detail to assess their analytical consequences. The statistical lesson is not that the treatment had a particular result, but that a design description, adverse-event counts, and planning assumptions cannot replace posted outcome estimates, uncertainty, and transparent methods.

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.

Several trial-specific details needed to interpret the primary outcome are not reported in the registry record. These include the reason for termination, the reason the 8-week data were not collected or analyzed for the one participant in the Premenopausal Women-Placebo arm, and the analysis population. The record does not provide participant flow by arm or describe completion of the glucose assessments.

The primary endpoint description refers to multiple categories or time points, but does not identify a single comparison. It does not specify which measurement from the 120 minute glucose tolerance test defined the primary analysis, how baseline and 8-week measurements were compared, or whether results were to be analyzed separately or jointly across the sex-specific arms. These analytical choices are not reported in the registry record.

No primary glucose values, treatment estimates, confidence intervals, or p-values are posted. No statistical analysis plan, missing-data approach, multiplicity strategy, or sample-size justification for the trial is reported in the registry record. Consequently, it is not possible to evaluate the precision of a treatment effect, assess whether a planned analysis was followed, or determine how incomplete observations may have influenced findings.

The adverse-event information is limited to the listed counts and risk groups; further details about event ascertainment, timing, and attribution are not reported. The enrollment total and terminated status provide context but cannot explain study conduct or the absence of outcome analyses. Together, these limitations restrict interpretation to the registered design and descriptive safety figures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of 1,25-dihydroxyvitamin D3, Treatment on Insulin Secretion and Muscle Strength in Pre-diabetic Persons — NCT04286529.
• Registry record last updated 2022-04-18; status last verified 2022-02.
• Results first posted 2022-04-18.
• 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 identifies NCT04286529 as a randomized, triple-masked, parallel Phase 1 study of calcitriol and oral placebo in pre-diabetic persons. Enrollment is listed as 17, and the study status is terminated. Four arms are described for men and premenopausal women receiving calcitriol or placebo. The calcitriol regimen is a 0.25mcg capsule daily for eight weeks.

The primary outcome is glucose levels, measured at baseline and 8 weeks in connection with a glucose tolerance test. The record notes that 8-week data were not collected or analyzed for one participant in the Premenopausal Women-Placebo arm. PROMIS 10 Questionnaire is listed as a secondary outcome. No outcome analyses are posted, and the registry record does not report the reason for termination, a statistical analysis plan, or the intended single glucose comparison.