The Diurnal Rhythm in Natriuretic Peptide Levels: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Diurnal Rhythm in Natriuretic Peptide Levels (NCT03834168), a na na study. The primary outcome is Plasma MRproANP.

2. Clinical Question

3. Trial Design

The registry describes a completed, single-group study sponsored by the University of Alabama at Birmingham. The record lists an enrollment of 42. The study started on 2019-04-01, reached primary completion on 2020-02-29, and has a completed status. The phase is listed as NA. These administrative details describe the registry entry; they do not establish how many participants contributed data to each outcome analysis.

Participants were to be healthy, self-identified African-American and white men. The study's stated aim refers to assessing natriuretic peptide rhythms in obese and African-American individuals compared with lean and white individuals. The primary outcome description specifically frames the comparison as obese versus lean. The registry does not provide the number of participants in each demographic or weight category for the primary outcome analysis.

The record lists a standardized study diet as the intervention. The primary outcome timeframe is about 24 hours on the inpatient study visit day after participants consumed study meals for 5 days. The diet therefore forms part of the study conditions under which the temporal measurements were planned; it is not described as a randomized intervention comparison.

Allocation is listed as NA and masking as none. The registry identifies the study model as single-group and cautions that the arms are not a like-for-like control comparison. The record does not report a detailed protocol for the measurement schedule, the assignment of participant categories, or the statistical model used to evaluate the rhythms. These design details matter because a comparison between observed participant categories does not, by itself, identify a causal effect of obesity or race.

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: A total of 42 participants agreed to participate in the study following the completion of the informed consent process and were assigned to each Arm/group. We had one study dropout and one participant was not able to complete the protocol. A total of 40 participants completed the study.

Overall Study

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 Plasma MRproANP, measured over About 24 hours on the in-patient study visit day after consuming study meals for 5 days.

The primary outcome is plasma MRproANP, measured in pmol/l. The registry says it is summarized using a median and an inter-quartile range and assessed over about 24 hours on the inpatient study visit day, after study meals for 5 days. The stated purpose is to assess the diurnal rhythm in circulating MRproANP among obese individuals and compare it with the rhythm among lean individuals.

A median describes the middle of an ordered set of measurements, while the inter-quartile range describes the spread of the central portion of those measurements. These summaries can convey both a typical level and variability without assuming that the measurements follow a symmetric distribution. This is a general explanation of the statistics, not a claim about the distribution of the study data.

Assessing a rhythm requires attention to how the measurement varies with time, rather than relying only on a single overall concentration. A time-dependent pattern may be described by features such as its level and timing. The registry does not report the specific sampling schedule, the method used to estimate the rhythm, or the observed median and inter-quartile range. It also does not provide a numerical estimate of the difference between obese and lean participants. The biological or clinical rationale for selecting MRproANP as the primary measure is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a time-varying biomarker question, but does not describe the statistical procedures used to answer it. The explanations below are general statistical context. They should not be read as a description of methods that the investigators necessarily used.

What does a median and inter-quartile range describe?

A median is the central value after measurements are ordered. The inter-quartile range describes the spread between the lower and upper quarters of that ordered distribution. Together, these summaries give information about a typical measurement and the variability among measurements. They can be useful when data are skewed or contain values that would strongly influence a mean. The registry specifies these summaries for plasma MRproANP, but does not report their numerical values. It also does not explain why this summary was selected or provide information about the distribution of the measurements.

Why does timing matter for a rhythm?

A diurnal rhythm is a pattern that changes over time within a daily cycle. To describe it, measurements need to be considered in relation to their timing. A summary that collapses all observations into a single value may omit the shape or timing of a pattern. Rhythm analyses can estimate features such as the timing of a peak, often called an acrophase, and the extent of variation around an average level. This is general background; the registry does not state which rhythm model, if any, was fitted, how measurements were timed, or how rhythm parameters were estimated.

The primary outcome timeframe is about 24 hours during the inpatient visit, following study meals for 5 days. This describes the intended assessment context, but not the frequency or exact timing of blood pressure and blood sampling. The registry also does not explain how missing time points, irregular sampling, or within-participant correlation were handled. Those details are important because repeated observations from the same participant are not generally independent of one another.

How should a comparison between participant categories be understood?

Comparing obese with lean participants can describe how observed measurements differ between those categories. Because the registry lists allocation as NA, masking as none, and the model as single-group, this is not described as a randomized treatment comparison. Random assignment, when used, can help balance measured and unmeasured characteristics between treatment groups. In a nonrandomized category comparison, differences in other characteristics may contribute to an observed contrast. The registry does not report an adjusted analysis or identify covariates included in any model.

For a general estimate of a group difference, an effect measure should be considered alongside its uncertainty. A confidence interval communicates a range of values compatible with the data and assumptions of the analysis. A p-value addresses compatibility with a specified null model, but does not express the size or practical importance of an effect. Neither a confidence interval nor a p-value for the primary result is reported in the registry record, so the statistical evidence cannot be evaluated from the posted outcome information.

What is an acrophase difference?

Acrophase refers, in general, to the timing of a rhythm's peak. A difference in acrophase can express how far apart the peak timings of two rhythms are. The registry names a secondary outcome as the acrophase difference in hours between MR-proANP and systolic blood pressure rhythms. That outcome could address timing, but a numerical estimate is needed to determine its observed size and direction. The record does not report its estimate, uncertainty, or the method used to calculate it.

What do the planning assumptions mean?

The registry includes sample-size planning assumptions based on the observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning illustrations, not the trial's own design justification. The registry does not report the sample-size justification used to plan this study. Planning calculations based on an observed effect should not be called observed power, and they do not replace an estimate of the effect's uncertainty.

For a general comparison, over-dispersion means that variability is greater than a chosen model expects. Ignoring it can make standard errors too small and statistical evidence appear more precise than warranted. The registry does not report whether over-dispersion was assessed or whether any model required such an adjustment. More broadly, the statistical analysis plan, model diagnostics, handling of repeated observations, and any recalculated estimates are not reported in the registry record. The available information therefore supports a methodological reading of the question and design, but not a reconstruction of the analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and names a primary plasma MRproANP outcome and a secondary outcome concerning the acrophase difference between MR-proANP and systolic blood pressure rhythms. The other outcome details are not reported in the registry record. Considering several outcomes or analyses can increase the chance that at least one result appears noteworthy by chance. A prespecified hierarchy, adjustment procedure, or other multiplicity strategy can help readers understand how multiple results were handled. Such a strategy is not reported in the registry record.

The registry lists two analyses, but does not describe their methods, hypotheses, or relationship to the outcome measures. It does not report whether analyses were prespecified, whether additional exploratory analyses were conducted, or whether any results were adjusted for multiple comparisons. Consequently, the posted record does not allow readers to distinguish confirmatory analyses from exploratory ones.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment entry is 42, but that does not establish the number with complete primary outcome measurements or the number included in each analysis. The record does not describe exclusions after enrollment, incomplete measurement series, imputation, or sensitivity analyses. These omissions matter for a time-dependent outcome because missing observations could affect estimates of the rhythm's shape or timing.

The registry does not report an intention-to-treat population or another defined analysis set. Because the study is not described as randomized, an intention-to-treat comparison should not be assumed. The record also does not state how eligibility, adherence to the study diet, or availability of blood pressure measurements affected inclusion in the outcome analyses. Without these details, the completeness and selection of the analyzed data cannot be assessed.

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 5% reporting threshold.

The posted adverse-event summary lists a lean group with 18 participants at risk and zero serious adverse events, zero other adverse events, and zero deaths. The obese group has 22 participants at risk and likewise lists zero serious adverse events, zero other adverse events, and zero deaths. No serious adverse-event terms are listed.

These entries describe the registry's reported counts, not a comprehensive assessment of safety. The record does not report the safety observation period, event definitions, methods of event collection, or whether events were actively solicited. It also does not give explanations for the differences between the at-risk group counts and the overall enrollment entry; the number assessed for a specific outcome should not be inferred from enrollment alone.

Zero reported events means no events were entered in these summary fields for the listed groups. It does not establish that the study procedures carry no risk, nor does it establish that every participant had complete safety follow-up. The registry record does not provide further detail with which to evaluate the completeness of safety reporting.

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

This study addresses a measurement question: how plasma MRproANP varies over the daily cycle among obese participants compared with lean participants, and how its timing relates to nocturnal blood pressure. The registry identifies the primary measure, its units, its summary format, and the inpatient assessment timeframe. It also names an acrophase comparison as a secondary outcome. These details make the research question understandable even though the outcome estimates are not reported.

The record does not show whether MRproANP differed between the participant categories, whether a diurnal pattern was detected, or how large or precise any difference was. It does not provide numerical results for the primary outcome or the blood pressure timing outcome. No conclusion about the presence, absence, or strength of a relationship can be drawn from the registry information alone. The lack of a reported result should not be mistaken for a null finding.

The study's single-group classification and nonrandomized participant categories also limit causal interpretation. A difference between obese and lean participants, if observed, would not by itself show that obesity caused the difference. The stated aim includes racial categories, but numerical results by race are not reported in the registry record. The entry therefore cannot establish whether race-related comparisons were analyzed or what their results were.

The standardized diet and inpatient measurement context define conditions for the intended assessment. They do not demonstrate that the findings, if available, would generalize to people studied under other conditions. The registry does not report an analysis of generalizability, a detailed sampling schedule, or the statistical model. Overall, the record documents a completed study question and some design features, but does not provide the results required to judge the observed biomarker rhythm or its relationship with blood pressure.

13. Why This Trial Matters Statistically

The statistical interest of this study lies in its focus on timing as well as concentration. A biomarker measured over a daily cycle may show patterns that an overall average or a single measurement cannot capture. The study's primary outcome is explicitly framed as a diurnal rhythm, and its secondary outcome concerns the timing difference between MR-proANP and systolic blood pressure rhythms. This makes the analysis question about both level and temporal alignment.

That question also makes the measurement plan important. Rhythm estimates depend on when measurements are collected and how observations within a participant are handled. The registry specifies an inpatient assessment of about 24 hours following study meals for 5 days, but does not provide the sampling schedule or modeling details. Without those methods, readers cannot assess how robustly the intended temporal patterns were estimated.

The design illustrates a distinction between describing groups and estimating a causal effect. The registry compares participant categories but does not describe random allocation. A category contrast may be informative about observed associations, while remaining vulnerable to differences between participants that are not accounted for in the analysis. The registry record does not report whether adjustment was used.

Finally, the entry shows why registration details and outcome reporting serve different purposes. It records the question, outcome definition, timeframe, and selected design features, but numerical outcome estimates and uncertainty are not reported. Those results are necessary for assessing the size and precision of any association. The statistical importance of the study question can therefore be recognized without treating the registry entry as evidence for a particular result.

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 study is that the registry record does not report numerical results for the primary or secondary outcomes. The plasma MRproANP median and inter-quartile range, group comparisons, estimates of rhythm features, and uncertainty measures are absent. As a result, neither the magnitude nor the precision of any observed pattern can be evaluated.

The design information is also incomplete for assessing the analysis. The registry identifies a single-group model, no masking, and allocation listed as NA, while describing lean and obese participant categories. It does not provide details of the statistical model, covariate adjustment, measurement schedule, handling of repeated observations, or analysis populations. The registry's warning that the groups are not a like-for-like control comparison is particularly relevant: any group differences would not establish causation.

The stated study population is healthy, self-identified African-American and white male participants, but the number of participants in each relevant subgroup and the analysis results by subgroup are not reported in the registry record. The record does not establish how representative the enrolled participants were or whether findings could be generalized beyond the study population and inpatient conditions.

Although enrollment is recorded as 42 and the adverse-event summary gives group-specific at-risk counts, outcome-specific completeness is not reported. Missing-data handling, exclusions, adherence to the standardized diet, and safety follow-up procedures are not described. The sample-size planning assumptions are identified as illustrations rather than the study's own design justification. These gaps constrain interpretation of both the study's statistical evidence and the completeness of the reported record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Diurnal Rhythm in Natriuretic Peptide Levels — NCT03834168.
• Registry record last updated 2024-02-05; status last verified 2024-01.
• Results first posted 2021-08-31.
• 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

NCT03834168, titled “The Diurnal Rhythm in Natriuretic Peptide Levels,” is a completed study sponsored by the University of Alabama at Birmingham. The registry lists an enrollment of 42, a start date of 2019-04-01, and a primary completion date of 2020-02-29. It describes healthy, self-identified African-American and white male participants and a standardized study diet.

The primary outcome is plasma MRproANP in pmol/l, summarized by median and inter-quartile range over about 24 hours after study meals for 5 days. The research question concerns diurnal patterns and a comparison between obese and lean individuals. The registry also lists an acrophase difference between MR-proANP and systolic blood pressure rhythms as a secondary outcome.

The model is listed as single-group, allocation as NA, and masking as none. Numerical outcome results, analysis methods, missing-data procedures, and multiplicity handling are not reported in the registry record. The adverse-event entries list zero serious events, zero other events, and zero deaths for both listed groups.