Beige Fat, Energy, and the Natriuretic Peptide System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Beige Fat, Energy, and the Natriuretic Peptide System (NCT04357964), a registered phase not stated study. The primary outcome is Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status.

2. Clinical Question

The broader scientific question in the registry description concerns possible links among obesity, race, the natriuretic-peptide system, beige adipose tissue, and energy expenditure. The description proposes that natriuretic-peptide deficiency might contribute to less beige adipose tissue and lower energy expenditure in obese and black individuals. These statements describe the investigators’ postulate; they are not findings established by the registry entries. The listed secondary questions concern associations between UCP1 expression and natriuretic-peptide markers, and differences in UCP1 expression by race. Results for those questions are not reported in the registry record.

3. Trial Design

The record identifies NCT04357964, titled “Beige Fat, Energy, and the Natriuretic Peptide System,” and lists the official title as “Beige Fat, Energy, and the Natriuretic Peptide System (ENDA-025-17S).” The sponsor is the VA Office of Research and Development. The study is marked completed, with a start date of 2020-04-13 and a primary completion date of 2022-10-31. Enrollment is listed as 137.

The listed group description is “obese and lean individuals.” The primary endpoint compares those groups on adipose-tissue UCP1 gene expression. The registry record does not describe a randomized allocation, and the comparison is not a like-for-like control comparison. It does not report how participants were recruited, how obesity status was defined, or whether other study procedures could affect the comparison. These details should not be inferred from the group labels.

The primary endpoint is specified for Study Day 1. Its population is all participants who had data for the endpoint, but the number with such data is not reported in the registry record. The record lists three outcome measures and three analyses, but does not provide enough information to match each analysis to a particular outcome or to describe all analysis procedures.

The registry description says the investigators proposed to quantify adipose-tissue gene expression and energy expenditure in states of natriuretic-peptide deficiency. UCP1 gene expression is the identified primary endpoint; the record does not report numerical energy-expenditure results. The listed secondary outcomes address UCP1 associations with natriuretic-peptide markers and UCP1 differences by race. Numerical results for these outcomes are not reported in the registry record. A sample-size justification, detailed protocol, and analysis plan 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: Enrolled subjects underwent a screening visit to determine eligibility for the study. The screening visit included a medical history, physical examination, calculation of BMI, and a blood draw for CMP, CBC, HbA1c, TSH, and free T4. A pregnancy test was completed on female subjects of child-bearing potential. Eligible subjects who still wished to participate in the study were then enrolled for the main study visit.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who had data for primary endpoint (adipose tissue UCP1 gene expression).

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 Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status, measured over Study Day 1.

The primary endpoint is relative adipose-tissue gene expression of UCP1, also called Uncoupling Protein 1. The registry record describes measurement using quantitative real-time reverse-transcription polymerase chain reaction, abbreviated qRT-PCR, with expression normalized to a housekeeping gene. The endpoint is expressed in fold change and is measured on Study Day 1. The stated comparison is obese versus lean individuals.

In general, gene-expression assays quantify a biological signal in a tissue sample. Normalizing the target signal to a housekeeping gene is intended to account for differences in the amount or quality of material being measured. The registry record identifies this normalization approach but does not report the specific housekeeping gene, assay details, laboratory procedures, or quality-control criteria.

UCP1 expression is relevant to the stated research question because the registry description concerns beige adipose tissue and energy expenditure. That context explains why UCP1 expression was selected as an endpoint; it does not mean that the endpoint directly measures beige-fat quantity, whole-body energy expenditure, or a clinical outcome. The record does not report evidence that a particular expression value corresponds to a particular amount of tissue or energy expenditure.

The planned summary is the median with an inter-quartile range. In general, the median describes the middle of an ordered set of observations, while the inter-quartile range describes the span of the central half. These summaries can describe skewed data without requiring a symmetric distribution. The actual median, inter-quartile range, group sizes, and comparison result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measurement of relative UCP1 expression, summarized by median and inter-quartile range. The registry record does not report the numerical summaries or the inferential procedure used to compare obesity-status groups. The statistical concepts below are general explanations, not claims about unreported methods in this study.

What do the median and inter-quartile range describe?

In general, the median is the central observation after measurements are ordered. It is less affected by unusually high or low values than the arithmetic mean. The inter-quartile range describes the middle portion of the distribution, from the lower quartile to the upper quartile. Reporting both can help readers understand the typical value and the spread of a distribution, especially when the data are skewed. These summaries do not by themselves test whether groups differ. For this study, the registry record specifies these summary measures but does not report their values.

What does qRT-PCR measure?

In general, qRT-PCR is a laboratory method used to quantify a target gene’s expression in a biological sample. Normalization to a housekeeping gene is intended to make target measurements more comparable by accounting for variation in the sample or assay. The registry record states that UCP1 expression was quantified using qRT-PCR and normalized to a housekeeping gene. It does not identify the housekeeping gene or provide enough assay detail to assess the laboratory method further. The endpoint is gene expression, not a direct measurement of energy expenditure or a clinical outcome.

What would a group comparison require?

In general, a comparison of two groups can be described with an effect estimate, an uncertainty measure such as a confidence interval, and a test result if a test is used. The choice of method depends on the measurement scale, distribution, study design, and analysis plan. A method suited to comparing medians may differ from one suited to comparing means. The registry record does not identify the statistical test, any model, covariate adjustment, or a confidence-interval method for the primary endpoint. No particular approach should be assumed.

The groups are defined by obesity status rather than by a stated random assignment. In general, randomization can balance measured and unmeasured factors on average, whereas a nonrandomized group comparison can be affected by differences between groups. Statistical adjustment may address some measured differences, but it cannot automatically remove all confounding. The registry record does not report whether adjustment was used, which variables might have been considered, or how group classification was established.

Why can dispersion matter?

In general, biological measurements can vary substantially among participants. If variability is greater than expected under a simple model, standard errors and test results based on that model may be unreliable. Over-dispersion is one term for variation beyond what a model assumes; it matters because an overly restrictive model can understate uncertainty. The registry record does not say that over-dispersion was assessed or that any particular model was used. Because the endpoint is summarized with a median and inter-quartile range, the record signals a distribution-focused summary, but it does not establish the distribution or analysis method.

How should planning illustrations be read?

In general, a sample-size calculation describes the number of participants or events needed under stated assumptions to target a specified power for detecting an effect. The registry record’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. These are planning illustrations, not evidence of the study’s original design and not observed power. Sample-size outputs are sensitive to the assumed effect, variability, allocation, test, and significance level. No original sample-size justification is reported in the registry record.

For non-time-to-event planning illustrations, the stated convention is participants per arm; for time-to-event illustrations, it is the total number of events. These conventions describe how a planning quantity is expressed, not the number actually enrolled or analyzed. The registry enrollment is 137, but that figure should not be substituted for the number contributing to the primary endpoint or treated as an analysis-specific sample size.

What can be learned from the record’s outcome listing?

The record identifies one primary endpoint and lists secondary questions involving natriuretic-peptide markers and race. It also lists three outcome measures and three analyses. In general, separate outcomes and comparisons may call for careful attention to multiplicity, because testing many hypotheses can increase the chance of at least one apparently unusual result. The registry record does not describe a multiplicity strategy, a hierarchy among secondary analyses, or which results were designated confirmatory. Numerical results and methods for those analyses are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint and secondary outcomes concerning associations of UCP1 expression with natriuretic-peptide markers and differences in UCP1 expression by race. It also lists three outcome measures and three analyses. The detailed mapping of analyses to outcomes, the planned hierarchy of questions, and any multiplicity adjustment are not reported in the registry record.

In general, when several hypotheses are tested, the chance of at least one false-positive result can increase if each test is interpreted independently. A prespecified primary endpoint can help distinguish the main question from supporting or exploratory questions, while multiplicity procedures can adjust inference across a family of tests. The registry record identifies the primary endpoint, but does not report whether any adjustment was planned or applied. Since the numerical results are not reported, the effect of any possible multiplicity approach cannot be assessed.

The primary-endpoint population is described as all participants with data for adipose-tissue UCP1 gene expression. The number meeting that description is not reported in the registry record. The record does not describe missing-data reasons, how missing endpoint values were handled, whether any imputation was performed, or whether sensitivity analyses were conducted. In general, missingness can affect both precision and the interpretation of a group comparison, particularly if the availability of data differs across groups or relates to the outcome.

The analysis populations for the secondary outcomes and any other analyses are not reported in the registry record. No intention-to-treat population is specified, and no such population should be inferred for this nonrandomized group comparison. The record does not state whether analyses included all participants with available measurements, a subset meeting additional criteria, or another defined population. These omissions limit assessment of which participants contributed to each result and how robust any findings might be.

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 adverse-event listing reports zero serious adverse events among 55 lean individuals at risk and zero among 22 obese individuals at risk. It lists 8 other adverse events among the 55 lean individuals at risk and zero among the 22 obese individuals at risk. The registry also lists 8 deaths for lean individuals and zero for obese individuals. These are the figures as recorded; the record does not give descriptions of the serious events because none are listed in the serious-event terms field.

The record does not report the causes, timing, circumstances, or relationship to study participation of the listed deaths or other adverse events. It also does not provide further explanation of how the adverse-event groups were assembled or how these counts relate to the overall enrollment of 137. The at-risk counts should therefore be read as the denominators listed for these adverse-event entries, not as the total enrollment or the primary-endpoint analysis population.

In general, adverse-event counts describe reported events within the reporting framework; they do not by themselves establish causation. Counts without fuller context cannot show whether events were anticipated, related to study procedures, or comparable across groups. The registry record does not provide those details, so the figures should not be interpreted as evidence that the study caused or prevented an event.

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

The record establishes that a completed study asked whether adipose-tissue UCP1 expression differed between obese and lean individuals, and that it identified related questions about natriuretic-peptide markers and race. It specifies the primary endpoint, its measurement approach, its summary statistics, and its time point. It does not report the primary endpoint’s numerical results or the inferential results for the secondary questions. The direction, magnitude, and precision of those comparisons therefore cannot be determined from the registry record.

The study description also sets out a broader postulate linking obesity and race with natriuretic-peptide deficiency, beige adipose tissue, and energy expenditure. That proposed biological explanation should be kept separate from the endpoint definition and from any results. UCP1 expression is the primary endpoint, but it does not by itself establish all parts of the proposed pathway. Numerical energy-expenditure results are not reported in the registry record.

In general, an association between a group characteristic and a measurement is not automatically causal. The record describes an obese-versus-lean comparison and does not describe random assignment. Any group difference, if present, could reflect other differences between participants as well as obesity status. The registry record does not provide the adjustment methods or participant details needed to assess that possibility.

Completion status indicates that the study is marked completed in the registry; it does not supply missing outcome estimates or establish the strength of evidence. Similarly, enrollment of 137 does not tell readers how many participants contributed data to the primary endpoint. The endpoint population is defined by data availability, but its size is not reported.

The adverse-event entries report the listed counts for lean and obese individuals, including deaths, but do not explain causes, timing, or relationship to study participation. Those entries should be interpreted as registry counts rather than causal conclusions. Overall, the available record defines research questions and reports limited safety counts, but it does not permit a conclusion about whether UCP1 expression differed or about the broader proposed biological relationships.

13. Why This Trial Matters Statistically

This study is statistically notable because it asks a group-comparison question using a biological measurement and a distribution-focused summary. Relative UCP1 expression is measured in adipose tissue, normalized to a housekeeping gene, and summarized by median and inter-quartile range. Those details matter: the endpoint is a laboratory measure, not a direct clinical outcome, and the chosen summary describes the distribution rather than providing a treatment effect.

The record also distinguishes a primary question from related secondary questions. Comparing UCP1 expression by obesity status is not the same as examining associations with natriuretic-peptide markers or differences by race. Each addresses a different relationship, and the broader hypothesis about beige tissue and energy expenditure encompasses more than the primary endpoint alone. The registry record does not report numerical results for these questions, so readers cannot assess the size or precision of the associations.

The nonrandomized nature of the listed comparison is important for interpretation. Groups defined by obesity status may differ in other ways, and those differences can complicate attribution of an observed association. The record does not report a covariate-adjustment strategy or sufficient detail to assess confounding. Describing the design accurately prevents a group comparison from being mistaken for a randomized treatment contrast.

Finally, this record illustrates why enrollment, endpoint population, and outcome results are distinct pieces of information. Enrollment is listed as 137, but the number with primary-endpoint data is not reported. The study is marked completed, yet the numerical primary and secondary results are not reported in the registry record. A complete interpretation depends on those results and on their uncertainty, not only on the registered question or completion status.

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 study-specific limitations of interpretation follow from the registry entries. First, the primary endpoint’s numerical summaries and comparison result are not reported in the registry record. Without those results, the direction, magnitude, and precision of the obesity-status comparison cannot be evaluated. The same applies to the listed secondary questions about natriuretic-peptide markers and race.

Second, the primary-endpoint population is described as participants with available UCP1 data, but its size is not reported. The record does not describe missing-data handling, reasons for unavailable measurements, or sensitivity analyses. This prevents assessment of how much data contributed to the endpoint and whether missingness could affect interpretation.

Third, the registry record describes obese and lean groups but does not state how participants were assigned or classified, how obesity was defined, or whether other characteristics were addressed analytically. Since the comparison is not a like-for-like randomized control comparison, possible confounding cannot be ruled out from the record. No adjustment strategy is reported.

Fourth, the endpoint is gene expression measured by qRT-PCR, not a direct measure of beige adipose-tissue amount, energy expenditure, or a clinical outcome. Although the study description connects these topics, the registry record does not report numerical energy-expenditure results or establish that changes in expression correspond to changes in those other measures.

Finally, the record does not report a sample-size justification, a detailed statistical analysis plan, multiplicity handling, or the specific statistical test for the primary endpoint. The planning assumptions described for sample-size illustrations are not evidence of the study’s original design. The adverse-event listing also lacks details on event timing, causes, and relationship to study participation. These limitations constrain what can be concluded from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Beige Fat, Energy, and the Natriuretic Peptide System — NCT04357964.
• Registry record last updated 2024-08-01; status last verified 2024-05.
• Results first posted 2024-08-01.
• 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

NCT04357964 is a completed study titled “Beige Fat, Energy, and the Natriuretic Peptide System,” sponsored by the VA Office of Research and Development. The registry lists enrollment of 137, a start date of 2020-04-13, and a primary completion date of 2022-10-31. The study concerns obese and lean individuals.

The primary endpoint is relative adipose-tissue UCP1 gene expression measured using qRT-PCR, normalized to a housekeeping gene, and summarized by median and inter-quartile range for Study Day 1. Secondary questions concern UCP1 associations with natriuretic-peptide markers and differences by race. Numerical results for the primary and secondary outcomes are not reported in the registry record.

The adverse-event listing records zero serious adverse events in both listed groups, other adverse events among lean individuals, and deaths among lean individuals. It does not report details explaining those counts. The registry record does not report the primary-endpoint analysis population size, missing-data methods, a statistical test, or the study’s sample-size justification.