Hyperpolarized Xenon-129 Magnetic Resonance Imaging and Spectroscopy of Brown Fat: Healthy Adult Volunteer Pilot Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hyperpolarized Xenon-129 Magnetic Resonance Imaging and Spectroscopy of Brown Fat: Healthy Adult Volunteer Pilot Study (NCT02220426), a na phase 1 study. The primary outcome is Brow Adipose Tissue Surface Area.

2. Clinical Question

3. Trial Design

This was a phase 1 pilot study sponsored by the University of North Carolina, Chapel Hill. The registry describes a single-group design, allocation as not applicable, and no masking. Enrollment was 17. The record lists the condition as Obesity, but the title and study summary describe healthy adult volunteers; it does not explain the difference in wording.

The intervention was xenon inhalation. Participants could inhale up to 5 doses of 750ml of hyperpolarized xenon-129 gas. The study summary says MRI was performed at 3 Tesla using a prototype surface coil and pulse sequence. Imaging was intended to assess image quality and the ability to visualize BAT and detect thermogenic activity, at thermoneutrality and under mild cold conditions.

The primary outcome was BAT surface area on Day 1. The registry describes deriving this measure from two-dimensional images acquired before and during cold exposure. It also lists change in BAT temperature as a secondary outcome. The record gives 2 outcome measures and lists 0 analyses.

The study start is recorded as 2015-09-01, with primary completion on 2016-07-01. Its status is terminated. The registry record does not explain the reason for termination or describe a separate comparator group. Consequently, the design can address the feasibility of image acquisition and the recorded imaging measures, but it does not establish a randomized comparison between interventions.

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: No imaging data were collected for 9 participants because the Xenon signal did not reach the needed threshold required for imaging.

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 Brow Adipose Tissue Surface Area, measured over Day 1.

The primary endpoint is BAT surface area derived from two-dimensional MR images. The registry describes images obtained before and during cold exposure, with each image evaluated for pixels whose signal intensity increased by more than 5% during cold stimulation relative to baseline. The area represented by BAT-positive pixels is used to estimate the activated BAT area within the image field of view for each subject. The stated timeframe is Day 1, and the measure is characterized as a mean of a continuous measure with standard deviation as its dispersion.

This endpoint is intended to quantify an imaging feature associated with activated BAT rather than to measure a clinical outcome. In general, converting image signal into an area provides a defined summary of the observed image pattern, which can be described across participants. The registry says that the subject-level areas were averaged, but gives no numerical mean or standard deviation. It also does not report the detailed image acquisition results or a numerical estimate of change. Thus, the endpoint definition indicates what was intended to be measured, not the magnitude or precision of the observed group result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it represents an area measured from images, and the registry describes the group summary as a mean with standard deviation. A mean gives a central summary of the measured values, while a standard deviation describes how dispersed individual measurements are around that mean. Both are useful for characterizing a distribution, but neither is reported numerically for this study. Without them, readers cannot assess the observed scale of the endpoint or its variability.

How is the image-based area defined?

The registry describes acquiring two-dimensional MR images before and during cold exposure. A pixel is classified as BAT-positive when its signal intensity increases by more than 5% during cold stimulation relative to baseline. The area associated with those pixels is then used to derive a subject-level BAT surface-area measure. In general, an image-derived area depends on both the classification rule and the spatial calibration of the image. The threshold defines which pixels count, while pixel dimensions determine the area represented by each counted pixel. This operational definition makes the endpoint more specific than a general judgment that BAT is visible, but it does not establish that the signal rule is accurate or reproducible.

The record says that the resulting value for all subjects was averaged. However, it also states that no imaging data were collected for 9 participants because the xenon signal did not reach the threshold required for imaging. The available description does not explain exactly how the phrase “all subjects” relates to participants without imaging data. It does not give the number contributing to the mean, a missing-data method, or an analysis population definition. These details matter because a group mean describes only the observations included in its calculation, and the participants with usable images may differ from those without them.

What does a confidence interval ordinarily add?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, while an interval around a mean also helps distinguish uncertainty in the group estimate from variation among individuals. No confidence interval is listed for the primary outcome. No numerical mean or standard deviation is reported either, so readers cannot reconstruct a confidence interval from the registry record. The record also lists 0 analyses, and it does not give an outcome model or inferential procedure.

Why is image availability part of the statistical interpretation?

When an intended measurement cannot be obtained, the issue is not only a smaller set of values to summarize. The inability to acquire the measurement may relate to the imaging signal itself, so the missing observations can be connected to the feasibility question. General statistical practice distinguishes data that are unavailable for reasons unrelated to the outcome from data whose absence may depend on the measurement process or participant characteristics. The registry record does not describe which missing-data assumptions, if any, were considered. It also does not report sensitivity analyses or a comparison of the participants with and without usable images.

Accordingly, a mean based only on imageable cases would answer a narrower descriptive question than a summary for everyone enrolled. This does not imply that either summary was calculated; the numerical result and analysis population are not reported in the registry record. The available information is sufficient to identify the image-acquisition threshold as a relevant source of missing endpoint data, but not to determine its effect on an estimate.

How should planning illustrations be read?

Any sample-size illustrations associated with the posted results are planning calculations based on fractions of an observed effect, not the study’s own design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record does not report a sample-size justification for this trial. It also describes this trial as single-group, so a hypothetical two-arm planning framework is not the same as the design that was conducted. Such illustrations can show how assumed effect size and design choices affect planning, but they are not observed power and do not supply missing outcome evidence.

In general, power is a property of a planned statistical test under specified assumptions; it is not a measure of whether a study result is true. Retrospective calculations based on an observed effect do not establish that a study was adequately designed, nor do they compensate for missing results. No observed effect estimate is numerically stated in the registry record, so the illustrations cannot be interpreted from the record alone as a direct account of the primary endpoint.

Finally, over-dispersion is a general concern when observed variability is greater than a model’s assumptions allow. It can make standard errors and confidence intervals unreliable if the model does not account for the extra variability. The registry does not report a model for the primary outcome or information that would permit assessment of over-dispersion. This is therefore a general methodological consideration, not a finding about this study.

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("Xenon Inhalation")
n   <- c(4)
m   <- c(3541)
sp  <- c(2474)
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  Xenon Inhalation  4  3541.000  2474.000  -395.686  7477.686

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome as BAT surface area and the secondary outcome as change in BAT temperature. It reports 2 outcome measures and 0 analyses. The record does not provide numerical results for either outcome, statistical tests, or a description of how any analyses were conducted.

Multiplicity arises when several outcomes or statistical tests are evaluated: the chance of at least one apparently notable result can increase as more tests are considered. In general, a prespecified analysis plan can clarify which outcome is primary and how additional analyses will be interpreted or adjusted. The registry record does not report a multiplicity strategy, an analysis plan, or whether any outcome analyses were performed outside the registry entry. It is not possible to determine from this information whether multiplicity adjustments were relevant to the analyses actually conducted.

Missing primary-outcome data are explicitly noted: no imaging data were collected for 9 participants because the xenon signal did not reach the required imaging threshold. The record does not report how many participants contributed to the primary endpoint summary, how missing measurements were handled, or whether sensitivity analyses were conducted. It does not describe an analysis population, such as a group defined by enrollment or by successful image acquisition. Those omissions limit assessment of whether the reported endpoint was intended to represent all enrolled participants or only those with usable images.

The record also does not explain why the study was terminated. No inference about the reason should be drawn from the status alone. The absence of a reported analysis plan or numerical endpoint results means that neither multiplicity handling nor the consequences of missing imaging measurements can be evaluated fully.

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’s safety entries list 0 serious adverse events among 13 at risk, 12 other adverse events among 13 at risk, and 0 deaths. The at-risk counts are those recorded for the safety group; they are not the same as the overall enrollment figure of 17. The record does not give the terms or descriptions for the other adverse events, so their nature and severity cannot be characterized from these entries.

These are descriptive counts, not a comparison between groups: the study has a single group and no separate control arm. A count of 0 serious adverse events means that none are listed for the recorded safety group; it does not establish that risk is absent. General interpretation of safety counts depends on the size and follow-up of the group, the events monitored, and how events were collected. The registry record does not provide enough detail about follow-up or event ascertainment to assess those features.

The record lists 0 deaths. It does not report a comparative safety analysis or provide a causal assessment attributing events to xenon inhalation. The counts should therefore be read as the safety information entered in the registry, not as proof of safety or a treatment-effect estimate.

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

This trial addresses a measurement question: whether hyperpolarized xenon-129 MRI can be used to detect BAT and characterize an image-derived area measure in healthy adult volunteers. The registry describes a specific approach based on changes in signal during cold exposure, and it reports that some participants did not have imaging data because the xenon signal failed to reach the required threshold. Those details are relevant to feasibility because successful acquisition is a necessary step before the intended image-based endpoint can be calculated.

The record does not state a numerical primary-outcome result, its standard deviation, or an uncertainty interval. It therefore cannot show the measured mean BAT surface area or the precision of that estimate. Nor does it give a numerical result for the secondary temperature outcome. The absence of these results prevents a quantitative assessment of the imaging findings from the registry record.

The single-group design also sets a limit on what can be concluded. There is no separate control group and no randomized comparison. The before-and-during-cold image approach is part of the measurement procedure; it does not create a between-group treatment contrast. The record cannot establish comparative effects or distinguish the imaging method’s performance from other influences through a controlled comparison.

This study is not a clinical-outcome trial in the information recorded. Its stated focus is imaging feasibility and the detection of BAT and thermogenic activity, not a patient benefit or a treatment decision. The safety counts are descriptive and do not establish either the presence or absence of risk beyond the recorded events. Taken together, the registry record documents the intended imaging method and a substantial image-availability constraint, but it does not provide enough numerical outcome information to judge the magnitude, variability, or reliability of the primary measure.

14. Why This Trial Matters Statistically

The statistical interest of this trial lies in the link between a technical imaging process and an endpoint defined from the resulting image. The endpoint is not simply whether a scan was attempted: it depends on obtaining an adequate xenon signal, classifying pixels by a stated response to cold exposure, and converting those pixels into an area measure. Separating those steps helps readers recognize that a missing image and a measured area are distinct parts of the feasibility question.

The record’s note that 9 participants had no imaging data because the signal did not reach the required threshold makes data availability central to interpretation. In an imaging pilot, failure to obtain a usable measurement is itself informative about the method’s feasibility. At the same time, a summary based on the measurements that can be obtained may not describe all enrolled participants. The record does not report the analysis population or a numerical outcome summary, so this distinction cannot be resolved quantitatively.

The study also illustrates why design and planning assumptions need to be kept separate. It is a single-group study, while the stated planning illustration assumes equal allocation between two arms. That illustration is not a description of the trial design, and it is not observed power. Recognizing the difference prevents a hypothetical calculation from being mistaken for evidence generated by the study.

Finally, defining an image-derived endpoint in detail does not substitute for reporting its observed distribution and uncertainty. The registry gives a rule for calculating BAT surface area but no numerical mean or standard deviation. This leaves a gap between the measurement definition and the evidence needed to assess what the study observed. The distinction is valuable beyond this particular trial: clarity about endpoint construction, image availability, analysis populations, and uncertainty is essential when interpreting exploratory imaging research.

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.

The most direct limitation in the registry record is the absence of a numerical primary-outcome result. Although the endpoint definition specifies how BAT-positive pixels contribute to a surface-area measure, the record does not give the mean, standard deviation, or another numerical summary. It also does not provide an uncertainty interval or outcome-analysis result. The magnitude and precision of the endpoint therefore cannot be evaluated.

Image availability is another specific concern. No imaging data were collected for 9 participants because the xenon signal did not reach the threshold required for imaging. The record does not explain whether the threshold failure was related to participant characteristics, technical conditions, or another factor. It also does not report how many participants contributed to the endpoint summary, how missing imaging data were handled, or whether results were examined under alternative assumptions.

The endpoint is derived from a two-dimensional image and uses a signal-increase rule during cold stimulation. The registry does not report validation of that rule, repeatability of the measurement, reader agreement, or the relationship between the image-derived area and another reference measure. These are not claims that the method lacks validity; they are questions the available record does not answer.

The single-group design has no separate comparator, and no masking is listed. The record does not describe a statistical analysis plan, multiplicity handling, or the reason the study was terminated. It lists a secondary temperature outcome but gives no numerical result for it. The safety entries list other adverse events without event terms. These reporting gaps, together with the missing imaging measurements, constrain interpretation of feasibility, endpoint performance, and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hyperpolarized Xenon-129 Magnetic Resonance Imaging and Spectroscopy of Brown Fat: Healthy Adult Volunteer Pilot Study — NCT02220426.
• Registry record last updated 2025-11-25; status last verified 2025-09.
• Results first posted 2025-11-25.
• 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

NCT02220426 is a phase 1, single-group pilot study sponsored by the University of North Carolina, Chapel Hill. It examines hyperpolarized xenon-129 MRI for detecting brown adipose tissue in healthy adult volunteers. Enrollment was 17; the registry status is terminated.

The intervention was inhalation of up to 5 doses of 750ml of hyperpolarized xenon gas. The primary outcome was BAT surface area from images acquired before and during cold exposure, with a signal increase of more than 5% used to identify BAT-positive pixels. Change in BAT temperature is listed as a secondary outcome. No imaging data were collected for 9 participants because the xenon signal did not reach the required threshold.

The record lists 0 outcome analyses and does not report a numerical result for the primary endpoint. Safety entries list 0 serious adverse events among 13 at risk, 12 other adverse events among 13 at risk, and 0 deaths. The reason for termination, outcome analysis methods, and handling of missing imaging data are not reported in the registry record.