Exploration of Blood Flow Regulation to Bone in Humans: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Exploration of Blood Flow Regulation to Bone in Humans (NCT04083794), a na na study. The primary outcome is Tibial Blood Perfusion.

2. Clinical Question

3. Trial Design

This completed study is described as a cross-sectional laboratory assessment, not a randomized clinical trial. The registry record lists an enrollment of 90 and identifies Spaulding Rehabilitation Hospital as the sponsor. The study began on 2018-05-31, reached primary completion on 2023-04-13, and has completed status. The phase and allocation are listed as not applicable, and masking is listed as none.

The record describes one laboratory-assessment group and explicitly says the study has no arms: all participants undergo the same procedures. The primary outcome description identifies 81 participants across two protocols, including 67 controls and 14 participants with SCI. These are different figures with different stated contexts: the enrollment entry is 90, while the primary outcome population description gives the group breakdown for the outcome. The registry record does not explain the difference, so it should not be interpreted as evidence about why participants were or were not included in that outcome population.

The study investigates tibial perfusion during physiological maneuvers, rather than assigning participants to competing treatment strategies. The listed maneuvers include isometric handgrip exercise, a cold pressor test, nitroglycerin, reactive hyperemia, and leg dependency. The record says that most participants completed only a subset of the maneuvers and that two protocols were involved. It does not report how maneuver assignment or completion varied by participant, protocol, or group.

The study summary describes interest in loading, muscle contraction, sympathetic activity, and systemic perfusion pressure, and proposes comparisons between able-bodied participants and those with SCI. Details of the procedures beyond the named maneuvers, the allocation of participants to protocols, and the statistical 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: The current study does not assign participants to arms; it is a cross-sectional assessment where all participants will undergo the same procedures. Upon enrollment, all participants underwent laboratory based assessments.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 81 participants include 67 controls and 14 SCI across 2 protocols. Thus, most individuals completed only a subset of the total physiological maneuvers. After quality control, unusable data was discarded and outcome measures are reported only in the subgroup of individuals (# of participants analyzed for each group included for each test below) analyzed with appropriate data. Reasons for unusable data: spasticity (SCI), unable to complete certain physiological stimuli, motion artifacts.

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 Tibial Blood Perfusion, measured over 1 day.

The primary endpoint is tibial blood perfusion, represented by tibial total hemoglobin content and expressed as a concentration in μM. The record describes measurement of hemoglobin content in response to several physical maneuvers, including isometric handgrip exercise, a cold pressor test, nitroglycerin, reactive hyperemia, and leg dependency. It states that the outcome is assessed over a timeframe of one day.

The study summary explains that the investigators developed a near infrared spectroscopy device to assess blood content in bone non-invasively. In this study, the endpoint is intended to help characterize changes in tibial blood content associated with physiological conditions and maneuvers. It is a continuous measure, and the registry identifies the summary measure as a mean with standard deviation as the dispersion measure.

The registry record cautions that absolute established values of tibial bone hemoglobin content are not available, so it does not provide an absolute minimum-to-maximum range. That makes the endpoint most interpretable as a measurement to compare across the specified contexts and groups, rather than as a value with a registry-defined normal range. The record does not report numerical endpoint results, subgroup estimates, or uncertainty intervals. It also does not explain how the endpoint relates quantitatively to blood flow beyond its stated use as an assessment of tibial perfusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: tibial total hemoglobin content is reported as a concentration in μM. The registry identifies the summary as a mean and the measure of dispersion as standard deviation. In general, a mean describes the central value of measured observations, while a standard deviation describes how dispersed individual observations are around that mean. These summaries can help characterize an outcome, but interpretation also depends on the number of observations contributing to each estimate and on the pattern of the data. Maneuver-specific means, standard deviations, and analyzed counts are not reported in the registry record.

In general, a confidence interval expresses a range of values compatible with the data and statistical model, and communicates uncertainty around an estimate. A narrow interval indicates greater precision than a wide interval, all else equal. The registry record does not report confidence intervals for the primary endpoint or for comparisons between groups. Without estimates and intervals, readers cannot determine how precisely any response or group contrast was measured.

The study is described as a single-group, cross-sectional assessment with no arms. That structure is different from a randomized trial in which participants are assigned to alternative interventions. The record's intended comparison is between controls or able-bodied participants and participants with SCI, alongside responses to physiological maneuvers. In general, the groups in a cross-sectional study may differ in other ways, and the record does not report a statistical adjustment plan. Accordingly, any group contrast would be descriptive unless supported by additional design and analysis information.

The record says that two protocols were used and that most participants completed only a subset of the maneuvers. This means that the endpoint may have different available observations across maneuvers. In general, repeated measurements on the same person are related, so analyses should account for that dependence when relevant. The registry record does not report whether measurements were repeated within participants in a way that was modeled, what statistical tests or models were used, or how protocol differences were addressed.

The primary outcome description states that data judged unusable after quality control were discarded and that outcome measures are reported only in the subgroup of individuals who were analyzed. This is a limited description of data processing, not a full missing-data method. In general, excluding unusable measurements can affect interpretation if the likelihood of exclusion is related to a participant's group, maneuver, or outcome. The record does not report exclusion counts, reasons by subgroup, or sensitivity analyses assessing the effect of missing measurements.

The study summary identifies several physiological factors of interest, including loading, muscle contractions, sympathetic activity, and systemic perfusion pressure. The listed endpoint description names the maneuvers but does not map each maneuver to a specific hypothesis or report a planned hierarchy of tests. In general, testing multiple outcomes, contrasts, or time points raises multiplicity concerns: the more opportunities to find an apparently notable result, the more important it is to specify primary comparisons and any adjustment strategy. The registry record lists one primary outcome measure but does not report the detailed comparison plan or multiplicity handling.

The sample-size section contains planning illustrations based on an observed effect, using 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. These are planning assumptions, not a description of the study's own design. This study is not a randomized two-arm comparison, and the illustrations should not be read as observed power or as proof that the study was adequately powered. The registry record does not report the trial's sample-size justification or a prospective power calculation.

The registry lists zero analysis records. This indicates that analysis results are not recorded in the registry entry; it does not establish that investigators conducted no analyses. The statistical model, handling of repeated observations, estimates, uncertainty, and inferential results are not reported in the registry record. In general, conclusions about statistical evidence require the estimate, its uncertainty, and an understanding of the analysis that produced it.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, tibial blood perfusion, but the outcome description encompasses responses to several physiological maneuvers and the study summary describes multiple mechanistic questions. The record does not identify a complete hierarchy of maneuver-specific hypotheses, planned contrasts, or a procedure for handling multiplicity. In general, when several comparisons are examined, chance findings become more likely unless the analysis plan and interpretation account for the number and relationship of tests. No multiplicity adjustment is reported in the registry record.

Missingness is relevant because the primary outcome description says that unusable data were discarded after quality control and that outcome measures are reported only in the analyzed subgroup. It also says most individuals completed only a subset of the total maneuvers. The record does not give the number of usable observations for each maneuver, the reasons for unavailable measurements, or whether completion and exclusion patterns differed between the control and SCI groups. It does not report an imputation method, a missing-data assumption, or sensitivity analyses. The reason for the difference between the enrollment entry and the outcome population is not reported in the registry record.

The analysis population is described only broadly as the subgroup with analyzed outcome measures. The record identifies 81 participants in the primary outcome population, including 67 controls and 14 participants with SCI across two protocols, but does not report maneuver-specific analysis populations. It does not state whether every listed comparison used the same participants or whether estimates were restricted to those with complete measurements for a particular maneuver. These details matter when interpreting comparisons, since the participants contributing to one estimate may differ from those contributing to another.

Thus, the record gives a limited account of quality control but not enough detail to assess the influence of missing or unusable data, the analysis population for each comparison, or the handling of multiple tests.

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.

The registry's safety entry is titled Laboratory Based Assessments. It lists 81 participants at risk for serious adverse events and 81 at risk for other adverse events. The reported counts affected are zero for serious events and zero for other events, and the deaths count is zero. No serious adverse event terms are listed.

These figures should be read as the event counts recorded in the registry entry, not as proof that no adverse experience occurred under any definition or that the procedures have no risk. The entry does not provide event descriptions, timing, severity breakdowns, or details about how events were collected or classified. It also does not explain the relationship between the safety population and the enrollment entry of 90 or the primary outcome population of 81.

In general, a zero count in a registry report is a statement about what was recorded for the stated group and reporting period. It does not establish that an event is impossible, and the strength of any safety inference depends on the completeness of monitoring and reporting. The record does not provide enough information to assess those features. The listed counts therefore describe the registry's reported safety data and should not be treated as a broader conclusion about safety.

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

The record establishes that investigators studied tibial blood perfusion in a laboratory-based, cross-sectional assessment involving controls and participants with SCI. It identifies tibial total hemoglobin concentration as the primary endpoint and lists maneuvers intended to examine physiological responses. The study summary describes hypotheses about loading and group differences. These details make the research question and broad measurement approach clear.

However, the registry record does not report numerical results for the primary endpoint, estimates of response to individual maneuvers, or comparisons between the groups. It also provides no confidence intervals, p-values, or other analysis results. Readers therefore cannot determine the size or direction of observed responses, how precise those estimates were, or whether any observed group differences were compatible with chance variation. No claim that a treatment works or does not work follows from this record: the study is not described as a treatment trial.

The endpoint is a concentration measurement of tibial hemoglobin content. The record says there are no absolute established values from which to give a minimum-to-maximum range. The measure is presented as an assessment of perfusion, but the record does not report a numerical calibration or a threshold for interpreting an individual value. Results, if available, would need to be understood in the context of the maneuver, group, and measurement method rather than against a registry-defined normal range.

The study's cross-sectional design can support description of measured physiology and comparisons between the stated groups, but it does not by itself establish why groups differ. The two-protocol structure, partial completion of maneuvers, and post-quality-control exclusions also limit what can be inferred without subgroup counts and analysis details. The registry entry is informative about study aims and design, but insufficient to judge the magnitude, precision, or robustness of the findings.

13. Why This Trial Matters Statistically

Clinical and physiological measurements are often interpreted as though they directly represent an underlying process. This study makes that issue visible by identifying a concentration of tibial total hemoglobin as its endpoint and using it to assess tibial perfusion. The record explicitly notes that absolute established values are unavailable, so interpretation depends on the measurement context and on comparisons rather than on a registry-defined absolute range.

The design also illustrates why a study's structure matters as much as its question. This is a cross-sectional assessment, not a randomized comparison of treatments. It brings together controls and participants with SCI, and considers responses to several physiological maneuvers. Such a design can characterize patterns of measured response, while the registry record does not establish a causal effect of group status or of a treatment.

There are multiple sources of statistical complexity: two protocols, several maneuvers, partial maneuver completion, and data removed after quality control. These features make maneuver-specific analysis populations and missing-data reporting important. Without those details, readers cannot know whether the same participants contribute to each comparison or how exclusions may have shaped the analyzed data.

The record lists the primary outcome but not numerical results or statistical estimates. This is an important distinction for evidence interpretation: a clearly stated question and endpoint do not, by themselves, establish the size or precision of a finding. The record therefore offers a useful example of how design information can be present while the statistical evidence needed to evaluate the central hypotheses remains unavailable.

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 this study from the registry record is that numerical primary outcome results are not reported. There are no posted mean values, standard deviations, group contrasts, confidence intervals, or test results. The entry consequently cannot show the magnitude, direction, or precision of responses to the physiological maneuvers, or of differences between the control and SCI groups.

The outcome description reports 81 participants across two protocols, including 67 controls and 14 participants with SCI, whereas the enrollment entry lists 90. The record does not explain this difference. It also does not state how many participants contributed usable measurements to each maneuver or whether the distribution of available data differed by group. Since most participants completed only a subset of maneuvers and unusable data were discarded after quality control, the missingness and analysis-population details would be important for assessing possible selection effects.

The registry record does not provide a full protocol or statistical analysis plan. In particular, it does not specify the exact comparison for each maneuver, the handling of repeated observations or protocol differences, the model or test used, adjustment for potential confounding, or any multiplicity strategy. The listed summary measure and dispersion measure do not substitute for those details.

Finally, the study is described as cross-sectional with no arms. Its group comparisons should not be interpreted as randomized treatment effects. The endpoint is a hemoglobin concentration used to assess perfusion, and the record says there is no established absolute range. These design and measurement considerations constrain interpretation even if numerical results become available. Further eligibility, recruitment, and procedural details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Exploration of Blood Flow Regulation to Bone in Humans — NCT04083794.
• Registry record last updated 2024-06-17; status last verified 2024-06.
• Results first posted 2024-06-17.
• 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 describes a completed, cross-sectional laboratory assessment of tibial blood perfusion in able-bodied participants and participants with SCI. It lists enrollment of 90, names Spaulding Rehabilitation Hospital as sponsor, and records a study start of 2018-05-31 and primary completion of 2023-04-13. The study has no arms and is not a randomized comparison.

The primary endpoint is tibial total hemoglobin content, reported as a concentration in μM and summarized as a mean with standard deviation. The outcome description names several physiological maneuvers and reports 81 participants across two protocols, including 67 controls and 14 participants with SCI. It states that most participants completed only a subset of maneuvers and that unusable data were discarded after quality control.

Numerical outcome results, analysis estimates, and details of the statistical plan are not reported in the registry record. Safety entries list zero serious events, zero other events, and zero deaths among 81 at risk. These entries describe the counts recorded, while the broader methods and reporting detail needed to assess results and safety are not available in the record.