Human Cerebral Blood Flow Regulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Human Cerebral Blood Flow Regulation (NCT04265053), a non-randomized early/phase 1 study. The primary outcome is Cerebrovascular Conductance (CVC) in Response to Hypoxia, Male vs Female.

2. Clinical Question

The primary question concerns whether the change in cerebrovascular conductance during hypoxia differs between male and female groups. Conductance is defined in the registry as cerebral blood flow divided by blood pressure, and the endpoint is the difference between its baseline value and its value during hypoxia. The registry describes an intended population of healthy young adults aged 18–40 years, with age and disease identified as potential confounding influences the study aims to mitigate.

These are distinct comparisons: the primary outcome is framed as a male-versus-female contrast during hypoxia, while the listed drug and placebo visits describe within-participant study procedures. The registry record does not report the order of those visits, a statistical comparison of indomethacin with placebo, or the results for either contrast.

3. Trial Design

This is a completed, early-phase study with a non-randomized allocation, no masking recorded in the overall design fields, and a parallel model. The registry lists enrollment of 42 and identifies the University of Wisconsin, Madison as sponsor. The recorded start date is 2021-04-12, primary completion date is 2025-03-31, and status is completed.

The brief summary describes an objective to examine how sex and sex hormones influence cerebral blood flow control in healthy young adults, while reducing potential confounding by age and disease. It proposes that differences in cyclooxygenase signaling may contribute to differences in cerebral vasodilator function. These statements describe the study's rationale and hypothesis, not findings. The record also says that differences and mechanisms may vary by brain region, and describes multimodal MRI assessment.

Male and female participants are each described as attending MRI twice: one visit with indomethacin and one with placebo. Both visits include hypoxia and hypercapnia, with cerebral blood flow measured using MRI sequences and hemodynamics monitored for safety and research. The arm descriptions call the visit design double-blind and placebo controlled. However, the registry's overall allocation field says non-randomized and its masking field says none. The record does not explain this difference, specify the visit sequence, or report whether visit order was counterbalanced.

The registry includes two outcome measures, but reports no analyses in the record summarized by these design fields. The endpoint described as primary is mean change in cerebrovascular conductance in response to hypoxia, compared between male and female groups. The registry gives an enrollment target or count but does not report the number of participants contributing data to that endpoint. It also does not report a sample-size justification, the statistical analysis plan, or participant flow through study visits.

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: Originally, healthy adults between 18-40 years of age were recruited for a study on NOS and COX to test sex differences in CBF. After the study was unable to obtain the drug (L-NMMA) to test the NOS mechanism, the protocol was amended to remove the NOS intervention. The new version of the study used Indomethacin to test COX as a potential mechanism explaining sex differences in CBF control. To do this, 2 MRI visits were conducted in a double-blind placebo controlled design.

Overall Study

Reasons for not completing this period:

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 Cerebrovascular Conductance (CVC) in Response to Hypoxia, Male vs Female, measured over up to 75 minutes for entire visit, but hypoxia lasts about 20 minutes.

The primary endpoint is cerebrovascular conductance (CVC) in response to hypoxia, expressed in mL/100g/min. The registry defines CVC as cerebral blood flow divided by blood pressure. The outcome is the change from baseline: baseline CVC is subtracted from CVC during hypoxia. The comparison of interest is this change between male and female groups. The stated measurement period is up to 75 minutes for an entire visit, while hypoxia itself is described as lasting about 20 minutes.

In general, expressing cerebral blood flow relative to blood pressure is intended to characterize flow in relation to the pressure driving it. A change from baseline focuses the endpoint on the response during the challenge rather than on the absolute conductance value alone. A group contrast in that change can address whether the observed response differs between the groups studied. It cannot, by itself, establish why a difference arose or whether it applies to other populations or settings.

The registry says the hypothesis is that women will exhibit 50-60% more vasodilation in response to hypoxia. That is a stated hypothesis, not an observed outcome. No group means, standard deviations, between-group estimate, confidence interval, or p-value for the primary endpoint is reported in the registry record. Consequently, the magnitude and precision of the observed primary comparison cannot be described from the recorded outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a continuous measurement, and the registry identifies the primary summary as a mean with standard deviation. General statistical interpretation of a mean comparison depends on the estimated group means, the amount of variability within each group, the number of participants contributing data, and the method used to account for the design. The registry record does not report the endpoint estimates or its analysis method, so those components cannot be assessed for this comparison.

What does a mean difference describe?

In general, a mean describes the central value of a continuous outcome in a group. A between-group contrast describes how far apart the group means are on the measurement scale. For this endpoint, that scale is mL/100g/min and the measurement is the change in CVC from baseline during hypoxia. The numerical contrast would describe the observed average difference, but would not by itself show whether individual responses were similar or widely spread. Standard deviations describe variability around group means; they are not the same as confidence intervals and do not directly quantify uncertainty in the estimated group contrast.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. Its width reflects statistical precision: a narrower interval indicates greater precision under that method, while a wider interval indicates more uncertainty. A confidence interval is not a guarantee that the true value lies within its endpoints. The registry record does not report a confidence interval for the primary outcome, so the precision of the male-versus-female estimate cannot be evaluated.

What does a p-value answer?

In general, a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It does not measure the probability that the null hypothesis is true, nor does it describe the size or importance of an effect. Interpretation would depend on the test, its assumptions, and whether the analysis matched the study design. The registry record does not report a primary-endpoint p-value or identify the test used. The stated significance level of 0.05 appears in the sample-size planning assumptions and should not be mistaken for a reported outcome p-value.

Why does the design matter?

General statistical methods should reflect how observations are assigned and collected. A non-randomized comparison between groups can be affected by differences between those groups, including factors not measured or adjusted for. The registry describes male and female groups as the primary comparison and records overall allocation as non-randomized. It does not report a statistical adjustment strategy or enough participant characteristics to judge comparability.

The record also describes repeated MRI visits within each sex group: indomethacin at one visit and placebo at another. In general, repeated measurements from the same participant are related, rather than independent. An analysis of the drug and placebo visits would ordinarily need to account for that within-participant structure. The registry does not report whether those visits were analyzed as paired observations, how visit order was handled, or whether the primary endpoint analysis used data from both visits. No treatment comparison should be inferred from the visit descriptions alone.

What is over-dispersion?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. It matters because standard errors can then be too small, making confidence intervals appear more precise and p-values more favorable than warranted if the model is not adjusted. This concept is most directly relevant to outcomes modeled as counts or rates. The primary endpoint is continuous, and the registry does not report a model or evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion affected this study's primary analysis.

How should planning illustrations be read?

The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. In general, a sample-size calculation estimates the number of participants needed under specified assumptions about effect size, variability, allocation, and statistical error rates. Changing an assumed effect changes the resulting planning requirement. These calculations are not observed power, do not demonstrate that an effect is real, and do not replace an analysis of the collected data.

The assumptions also specify that time-to-event calculations would report total events, while other calculations would report participants per arm. The primary endpoint is continuous rather than time-to-event. No numerical planning values, variability assumptions, or justification for the original enrollment are reported in the registry record. The planning illustration should therefore be distinguished from the trial's own design justification, which is not reported.

These general principles explain what would be needed to interpret an analysis, but they cannot fill gaps in the record. Without endpoint estimates, uncertainty measures, participant counts for the analyzed outcome, and the statistical method, the strength and precision of the primary comparison remain unknown.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Hypoxia Male Indomethacin", "Hypoxia Male Placebo", "Hypoxia Female Indomethacin", "Hypoxia Female Placebo")
n   <- c(19, 22, 16, 17)
m   <- c(2.44, 4.9, 4.32, 9.04)
sp  <- c(4.59, 10.4, 4.27, 11)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Hypoxia Male Indomethacin  19  2.440  4.590  0.228  4.652
CARM  Hypoxia Male Placebo  22  4.900  10.400  0.289  9.511
CARM  Hypoxia Female Indomethacin  16  4.320  4.270  2.045  6.595
CARM  Hypoxia Female Placebo  17  9.040  11.000  3.384  14.696

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, but the information describing the primary endpoint does not explain how multiple outcomes or multiple comparisons were handled. The statistical plan, including any hierarchy of outcomes, adjustment for multiple testing, or designation of exploratory analyses, is not reported in the registry record. The number of analyses recorded is zero, so no analysis-specific multiplicity method can be identified from these entries.

Multiplicity matters in general when researchers perform several statistical tests: the chance of obtaining at least one apparently unusual result can increase as the number of tests increases. Whether adjustment is appropriate depends on the study questions and analysis plan. The available record does not establish how many comparisons were planned or performed, so no conclusion about the consequences of multiplicity is possible.

Missing-data handling is also not reported. The record does not state how many participants completed each visit, contributed measurements to the primary endpoint, or had incomplete MRI or physiological data. It does not describe imputation, exclusion rules, or sensitivity analyses. Consequently, the extent and possible influence of missing outcome data cannot be assessed.

The analysis population is not described. The registry does not specify whether analyses were based on all enrolled participants, participants completing both visits, or another defined group. Nor does it report an intention-to-treat approach or a per-protocol analysis. These omissions limit interpretation of any estimate that might appear elsewhere in a complete results report; no such primary estimate is reported in the registry information.

12. 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 four adverse-event groups: male participants during placebo and indomethacin visits, and female participants during placebo and indomethacin visits. The at-risk counts are 24 in each male group and 18 in each female group. Serious adverse events are recorded as 0 for all four groups, and deaths are also recorded as 0 in all four groups.

Other adverse events are recorded as affecting 3 male participants during placebo, 0 during indomethacin, 6 female participants during placebo, and 2 during indomethacin. The registry does not provide event terms for these non-serious events, so their nature and clinical importance cannot be described. The record also does not report timing, recurrence, severity, relatedness to study procedures or drug, or details of how events were collected.

These are descriptive counts, not a statistical comparison. The indomethacin and placebo visits occurred within the study groups, but the record does not report an analysis that accounts for repeated visits or establishes causation. The absence of recorded serious events in these entries does not establish that no other harms occurred or that the interventions have equivalent safety. The registry record does not report a formal safety analysis.

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

The record establishes that a completed study was designed to examine cerebral blood flow regulation, including a primary comparison of mean CVC change during hypoxia between male and female groups. It defines CVC, describes the baseline-to-hypoxia change, names the unit, and outlines indomethacin and placebo MRI visits. Those details clarify the research question and measurement strategy.

The record does not report the primary endpoint results. It contains no group means, standard deviations, effect estimate, confidence interval, or p-value for the male-versus-female comparison. Therefore, the direction, magnitude, and precision of any observed difference cannot be determined from the registry record. The stated expectation of 50-60% more vasodilation in women remains a hypothesis, rather than a result.

The record also does not establish whether indomethacin changed CVC relative to placebo. Although both visits are described for male and female participants, the analysis of those visits is not reported. Visit order and the methods for accounting for repeated observations are not reported either. The described procedures alone cannot establish a treatment effect or a mechanism involving COX signaling.

More generally, a finding in the study population would not automatically establish the same response in other ages, people with disease, or other settings. The stated objective focuses on healthy young adults aged 18–40 years, and the record does not report participant-level characteristics that would define the enrolled sample more fully. This does not diminish the value of a carefully designed physiological question; it defines the scope within which any result would need to be interpreted.

The appropriate conclusion from the available registry information is limited: the study was completed and the registry describes its rationale, outcome definition, procedures, and adverse-event counts. It does not report the statistical results needed to conclude whether the primary group contrast was observed or how precisely it was estimated.

14. Why This Trial Matters Statistically

This study raises a statistical question in which the biological comparison and the measurement strategy are closely connected. The primary endpoint is not simply cerebral blood flow at one time point: it is conductance, defined as flow relative to blood pressure, and the outcome is a change from baseline during hypoxia. Making that definition explicit helps distinguish the physiological quantity from a raw flow measurement and clarifies the contrast the investigators intended to study.

The record also illustrates why design labels need to be read together. It identifies the overall study as non-randomized, while arm descriptions refer to double-blind, placebo-controlled drug and placebo visits. These statements concern different aspects of the design, but the registry does not explain their relationship. A statistical interpretation depends on knowing which comparisons were randomized, which measurements were repeated within participants, and what analysis addressed those features.

There is also a useful distinction between a biological hypothesis and an empirical estimate. The proposed sex difference and COX mechanism motivate the study, but neither is established without results. The planned sample-size illustration is likewise conceptually different from an observed analysis: planning assumptions cannot substitute for estimates and uncertainty based on the collected endpoint data.

Finally, outcome reporting is central to statistical interpretation. Enrollment and a clear endpoint definition do not reveal the observed effect, its variability, or its precision. The absence of primary estimates in the registry record means readers cannot judge whether the data were compatible with a small difference, a larger difference, or no clear distinction. This makes the registry useful for understanding the question and design, but insufficient for assessing the primary result.

15. 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.

A central limitation of the available record is that it does not report the primary endpoint result or the analysis used to obtain it. Group means, standard deviations, confidence intervals, p-values, and the number of participants contributing endpoint data are not reported. Thus, the primary comparison cannot be evaluated for magnitude, precision, or statistical compatibility with different values.

The registry contains potentially discordant design descriptions: overall allocation is non-randomized and masking is none, while the male and female arm descriptions call the two MRI visits double-blind and placebo controlled. The record does not explain the distinction, specify how participants were assigned to visit order, or describe who was masked. These missing details restrict assessment of bias and of the appropriate analysis for the repeated visits.

Participant characteristics, actual age distribution, eligibility details, and participant flow are not reported in the endpoint information. Although the study objective refers to healthy young adults aged 18–40 years, the record does not establish how closely the enrolled participants matched that description or how many completed each procedure. Missing-data methods and analysis populations are also not reported.

The record describes two outcome measures but does not report a statistical plan, a multiplicity strategy, or the analyses performed. It also gives no event terms for non-serious adverse events. These gaps limit interpretation of both efficacy-related outcomes and safety counts. The registry's completed status does not itself provide evidence about the direction or certainty of the primary outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Human Cerebral Blood Flow Regulation — NCT04265053.
• Registry record last updated 2026-06-12; status last verified 2026-05.
• Results first posted 2026-06-12.
• 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.

19. Record Summary

NCT04265053, titled “Human Cerebral Blood Flow Regulation,” is recorded as a completed early-phase study sponsored by the University of Wisconsin, Madison. The registry lists enrollment of 42, non-randomized allocation, no masking in the overall design fields, and a parallel model. Its stated objective concerns cerebral blood flow regulation in healthy young adults aged 18–40 years.

The primary endpoint is mean change in cerebrovascular conductance during hypoxia, comparing male and female groups. The record describes indomethacin and placebo MRI visits involving hypoxia and hypercapnia. It reports no primary endpoint estimates or analyses, so the observed group difference and its precision are not reported in the registry record.

Adverse-event entries record no serious events and no deaths across the four listed groups, with other adverse events recorded for some groups. Event descriptions and a formal safety analysis are not reported.