Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate (NCT01950520), a randomized phase 2 study. The primary outcome is Resting Energy Expenditure at Low Temperature.

2. Clinical Question

3. Trial Design

This Phase 2 study is recorded as randomized, double-masked, and using a crossover model. It is listed as completed, with enrollment of 47. The sponsor is the National Institute of Diabetes and Digestive and Kidney Diseases. The study began on 2014-02-07, and primary completion is recorded as 2022-12-17. These dates and design labels describe the registry entry; they do not establish which participants completed each study procedure or contributed to each outcome.

The study is divided into three cohorts with differing objectives and intervention schedules. Cohort 1 concerns non-shivering thermogenesis. Its description refers to temperature blocks, including low temperature and 27°C, and repeated interventions. The primary outcome is from this cohort and is defined at low temperature. Cohort 2 concerns effects of anti-obesity drugs on basal metabolic rate; the description says interventions were administered in random order during one-day stays. Cohort 3 concerns mirabegron and brown fat activity; its description refers to randomized order during overnight inpatient stays.

The crossover label means participants may receive more than one condition or intervention over time, permitting within-participant comparisons in principle. That is a general explanation of crossover designs, not a statement about the exact analysis used in this trial. The registry record does not report the complete sequence schedule, washout periods, allocation procedures, masking procedures, or the statistical model used to account for repeated observations. The intervention descriptions are also incomplete. Therefore, the design label alone is not enough to reconstruct the trial's full conduct or its intended comparisons.

The registry lists a primary endpoint for Cohort 1 but does not report a primary outcome analysis. It records no analyses. The study's completed status should not be read as evidence that results were posted or that each planned cohort question was answered in the 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: Cohort 1

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 Resting Energy Expenditure at Low Temperature, measured over Cohort 1: Days 1-17.

The primary endpoint is resting energy expenditure (REE) at low temperature, measured in kcal/min. The registry defines it as REE at a temperature just above the participant's placebo shivering threshold. It is a continuous measure, with the endpoint parameter described as a mean and dispersion described as a standard deviation. The stated timeframe is Cohort 1: Days 1-17.

In general, REE describes energy use while at rest. Measuring it during cold exposure near an individual's shivering threshold is relevant to the study's focus on non-shivering thermogenesis: energy expenditure in the cold before shivering begins. The endpoint is therefore intended to quantify a physiological response under a specified temperature condition. This is a description of the measure's rationale, not evidence that an intervention changed REE.

The registry record does not report the mean REE for any intervention, a standard deviation, a treatment contrast, or a confidence interval. It also does not report how the threshold was determined in practice, how missing measurements were handled, or whether the reported timeframe reflects all planned observations. Without posted endpoint values and an analysis, the direction, size, and precision of any difference cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design mean?

In general, a crossover study has participants receive more than one intervention or condition over time. Each participant can then contribute measurements under multiple conditions, so an analysis may compare observations within the same person. Such comparisons can account for stable differences between participants, but they must also address time, sequence, and possible carryover effects. The registry labels this study a crossover, but does not report the analysis model, sequence effects, carryover assessment, or washout periods. It is not possible to tell from the label alone how the posted analysis handled these issues.

What does randomization contribute?

Random allocation is generally intended to reduce systematic differences in which intervention is received, especially when assignment is concealed and implemented as planned. The record calls the study randomized and describes random intervention order in Cohort 2 and Cohort 3, as well as block randomization of chamber temperature in Cohort 1. It does not give complete allocation details or describe how randomization was generated or concealed. These general purposes of randomization should not be mistaken for evidence that all potential sources of bias were eliminated.

How should the mean and standard deviation be understood?

The primary outcome is specified as a mean of a continuous measure, with standard deviation as its dispersion statistic. In general, a mean describes the central value of measurements, while a standard deviation describes their spread among observations. The standard deviation is not the same as the uncertainty in the estimated mean or the uncertainty in a treatment contrast. A confidence interval for an estimate is commonly used to express that inferential uncertainty. The registry record reports no primary mean, standard deviation, contrast, or confidence interval, so none can be interpreted for this outcome.

Why does the repeated-measure structure matter?

When one participant contributes measurements under multiple conditions, those measurements are usually correlated rather than independent. General methods for crossover data account for that correlation; treating every measurement as if it came from a different person can give misleading uncertainty. The appropriate approach depends on the actual design, outcome availability, and analysis plan. The registry record does not report a statistical model or enough detail to determine how within-participant correlation was handled. It would be speculation to name a particular paired test, mixed model, or other procedure as the trial's method.

What can a p-value or confidence interval say?

In general, a p-value summarizes how incompatible the observed data are with a specified null model, conditional on the analysis assumptions. It does not measure the probability that a treatment works, and it does not describe the size or practical importance of an effect. A confidence interval gives a range of estimates compatible with the data and model, and helps show precision. Neither is reported for the primary endpoint in this registry record. The completed status and enrollment count do not allow these quantities to be reconstructed.

Why might over-dispersion matter?

For general count outcomes, over-dispersion occurs when observed variability exceeds what a chosen count model expects. If not addressed, uncertainty can be understated. That concept is not directly applicable to the primary endpoint, which is continuous, and the registry does not describe an over-dispersion analysis. It is mentioned only as a general statistical consideration, not as a feature established for this study.

Can the planning sample-size illustration be interpreted as trial power?

A planning sample-size calculation is an illustration of the number of participants per arm that might be needed under stated assumptions. It is not a measure of the probability that this completed study detected an effect, and it is not observed power. The registry's sample-size assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. However, the primary outcome has fewer than two arms in the analysis record, and no observed primary effect is reported. The sample-size illustration therefore cannot establish the trial's achieved power or precision for the primary endpoint. The record does not report the trial's own sample-size justification.

What is the practical limit of the methods information?

The registry provides design labels, endpoint definitions, and some cohort descriptions, but not the analysis details needed to reproduce an inferential result. The statistical plan, handling of missing data, analysis populations, multiplicity strategy, and any interim analyses are not reported in the registry record. These omissions prevent assessment of whether the intended analyses were followed or how robust any result might be. No statistical procedure should be attributed to the study unless it is recorded.

10. Multiplicity, Missing Data and Analysis Populations

The study describes multiple objectives across three cohorts and several intervention conditions. When an investigation examines multiple outcomes, doses, conditions, or contrasts, there is a general risk that chance findings may arise if many statistical tests are conducted. Multiplicity methods can define which comparison is primary, adjust inference across a family of tests, or otherwise distinguish confirmatory from exploratory analyses. The registry record does not report a multiplicity strategy, the complete planned comparison set, or analyses. It is therefore not possible to determine how multiple questions were intended to be handled.

The record names a primary outcome for Cohort 1, but does not report its results. It does not provide an analysis population, participant flow, or the number of participants with available primary endpoint measurements. Although total enrollment is listed, it cannot be used to infer how many participants completed each cohort or contributed measurements. The registry record does not report how missing data were addressed, whether any participants were excluded from analyses, or whether an intention-to-treat or other population was used.

These are important distinctions in a crossover study because incomplete sequences or missing measurements can affect which within-participant comparisons are available. In general, methods for missing data require assumptions about why observations are absent. The record does not describe those assumptions or any sensitivity analyses. No conclusion can be drawn about the impact of missingness or multiplicity on the results because no primary analyses are reported.

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 lists serious adverse events, other adverse events, and deaths separately for the reported groups. For every listed group, the number with a serious adverse event is 0 and deaths are 0. The number at risk is reported by group: 16 for each Cohort 1 condition, 18 for each Cohort 2 condition, and 13 for each Cohort 3 condition. These are group-specific figures and should not be added to create a participant total, particularly because the study is a crossover design.

Other adverse events are not all zero. The registry lists 1 affected participant for Cohort 1 Low Temperature: Magnesium; 1 for Cohort 1 High Temperature: Proprannolol; and 1 for Cohort 1 High Temperature: Pindolol. In Cohort 2, it lists 5 for Naltrexone, 2 for Qsymia, 5 for Topiramate, and 2 for Phentermine. In Cohort 3, it lists 1 each for Placebo, Mirabegron 50mg, and Mirabegron 200mg. These are counts within the recorded groups, not adjusted comparisons or estimates of comparative risk.

Zero serious events in the listed groups does not establish that an intervention has no risk. The counts are descriptive, and the record does not provide a comparative safety analysis or further detail about event types beyond the listed information.

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

The record documents a randomized, double-masked crossover study of healthy volunteers, with several physiological and drug-related objectives. Its primary outcome is resting energy expenditure at low temperature in Cohort 1. This establishes what the registry identifies as the main endpoint; it does not establish what the measurements showed.

No primary outcome results or statistical analyses are reported. Consequently, the registry record does not support a statement about whether REE differed between placebo and any intervention, the magnitude or direction of a difference, or its precision. It also does not support conclusions about basal metabolic rate in Cohort 2 or brown fat activity in Cohort 3. Those are stated study objectives, not posted findings.

In general, a treatment comparison should be interpreted using its estimate, uncertainty, design, and outcome measurement together. A result from a crossover study also needs to be understood in light of the participant-level repeated measurements and the analysis used. Because the record does not include those results or methods, no intervention effect can be inferred from the study description or from the adverse-event counts.

The study is listed as completed and has an enrollment of 47, but completion and enrollment do not substitute for reported outcome data. The record's safety figures are descriptive counts, not evidence about energy expenditure or treatment efficacy. Overall, the registry entry allows readers to identify the study question and some design features, while leaving the principal efficacy questions unanswered in the posted record.

13. Why This Trial Matters Statistically

This trial illustrates a recurring statistical challenge in mechanistic clinical research: a single study record can cover distinct biological questions, cohorts, and intervention comparisons. The primary endpoint is a physiological measure of energy expenditure under a specified low-temperature condition, while the other stated objectives concern basal metabolic rate and brown fat activity. Keeping those questions separate is essential; evidence about one measure or cohort would not automatically answer another objective.

The crossover design is also statistically important. In general, repeated observations from the same participant can be informative because they allow within-person comparisons, but they call for analysis that recognizes the dependence among measurements and the possibility of time or sequence effects. A design label is not enough to evaluate whether those features were handled appropriately. Here, the registry record does not report the analysis model or primary outcome estimates.

The entry also makes clear why a completed status and a stated enrollment are not substitutes for results. Without endpoint-specific data, an estimated contrast, and a measure of uncertainty, readers cannot judge the magnitude or precision of the primary finding. The absence of reported analyses limits both statistical interpretation and comparison with other research. These limitations do not show that the study lacked value; they define what can be concluded from the registry record itself.

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 primary limitation for interpretation is that the registry record does not report primary outcome results or analyses. No intervention-specific REE estimates, contrasts, uncertainty intervals, or p-values are available in the entry. The record therefore cannot support an estimate of the primary outcome effect or its precision.

Design and analysis details are incomplete. Although the study is labeled randomized, double-masked, and crossover, the complete intervention schedules and allocation procedures are not reported. The available cohort descriptions are truncated. The record does not report washout periods, the model used for repeated observations, handling of period or sequence effects, or any interim analyses.

The enrollment figure does not describe the number of participants who contributed to each endpoint or analysis. Participant flow, missing outcome measurements, exclusions, and analysis populations are not reported. The multiplicity strategy and the trial's own sample-size justification are also not reported in the registry record. These gaps prevent assessment of how the planned questions were prioritized, how missingness may have affected estimates, or whether the available information was adequate for a particular comparison.

The study population is described as healthy, lean adult males ages 18 to 35. Results, if reported, would need to be interpreted in that context; the record does not establish applicability to other populations. In this case, the primary efficacy results are absent, so even interpretation within the stated population is not possible from the posted data.

Safety information is also limited to group-level counts. The record provides no serious adverse events or deaths in the listed groups, but the counts do not establish comparative safety and do not replace detailed event descriptions or analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate — NCT01950520.
• Registry record last updated 2024-10-16; status last verified 2024-06-11.
• Results first posted 2024-10-16.
• 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

NCT01950520 is a completed Phase 2 randomized, double-masked crossover study titled “Study of Human Non-Shivering Thermogenesis and Basal Metabolic Rate.” It lists enrollment of 47 and describes three cohorts focused on non-shivering thermogenesis, drug effects on basal metabolic rate, and mirabegron's effects on brown fat activity. The named primary outcome is mean resting energy expenditure at low temperature in Cohort 1, measured in kcal/min, with standard deviation as the stated dispersion.

The registry record does not report primary outcome results or statistical analyses. It lists no serious adverse events and no deaths in the reported groups, alongside some other adverse-event counts. Because participant flow, missing data, analysis populations, and statistical methods are not reported, the record supports description of the study design and endpoint but not an estimate of intervention effects or their precision.