This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Intranasal CO2 for Allergic Rhinitis (NCT00618410), a randomized na study. The primary outcome is Change From Diluent Challenge Contralateral Secretion Weight at Antigen Challenge.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00618410 |
| Phase | NA |
| Condition | Allergic Rhinitis |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 13 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Chicago |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with allergic rhinitis, also described in the registry summary as hayfever. The primary endpoint excludes one patient who did not complete the second crossover intervention. The registry record does not report further eligibility details or describe the characteristics of the enrolled participants.
Intervention
Nasal carbon dioxide, USP, was administered 30 minutes before nasal challenge. The study’s stated purpose was to better understand how carbon dioxide affects allergic-rhinitis symptoms and whether its effect on an antigen challenge could help predict a beneficial effect in seasonal allergic rhinitis.
Comparator
The comparator was nasal placebo, also administered 30 minutes before nasal challenge. The study is recorded as randomized, double-masked, and crossover. The registry record does not report the intervention sequence, how masking was maintained, or whether a washout period was used.
Primary question
The primary outcome was the change in contralateral secretion weight, in milligrams, from diluent challenge to antigen challenge. The registry reports a median of 6.0 for carbon dioxide and 19.6 for placebo, with full ranges of -3.1 to 54.1 and 0.0 to 55.2, respectively. These descriptive summaries alone do not establish the size or statistical uncertainty of a within-participant treatment effect.
3. Trial Design
The registry describes a randomized, double-masked crossover study sponsored by the University of Chicago. Its recorded phase is NA, and its status is completed. Enrollment is listed as 13. The record lists allergic rhinitis as the condition and carbon dioxide, USP, and placebo as the interventions. Both were administered nasally 30 minutes before a nasal challenge.
In general, a crossover design exposes participants to more than one intervention, allowing comparisons within the same participant. This can account for stable differences between participants, but the interpretation depends on details such as treatment sequence, period effects, and carryover. The registry record does not report the sequence, period-specific results, washout arrangements, or methods for assessing carryover. It is therefore not possible to assess those design features from the record.
The registry lists a study start of 2008-02 and primary completion of 2008-04. The brief summary frames the study as an investigation of whether carbon dioxide affects symptoms during an antigen challenge, with the challenge response considered as a possible predictor of benefit in seasonal allergic rhinitis. The record does not establish that this challenge measure was validated as a predictor, nor does it describe a treatment trial measuring seasonal symptoms.
For the primary outcome, the registry states that one patient who did not complete the second crossover intervention was excluded. The carbon dioxide and placebo outcome summaries each list 12 participants. These counts describe the posted endpoint summaries; they do not establish how every participant contributed to every other outcome or analysis. Further details of allocation procedures, masking procedures, and the planned statistical analysis 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.
First Intervention
| Stage | Carbon Dioxide, Then Placebo | Placebo, Then Carbon Dioxide |
|---|---|---|
| STARTED | 7 | 6 |
| COMPLETED | 7 | 6 |
| NOT COMPLETED | 0 | 0 |
Washout Period (2 Weeks)
| Stage | Carbon Dioxide, Then Placebo | Placebo, Then Carbon Dioxide |
|---|---|---|
| STARTED | 7 | 6 |
| COMPLETED | 7 | 5 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | Carbon Dioxide, Then Placebo | Placebo, Then Carbon Dioxide |
|---|---|---|
| Physician Decision | 0 | 1 |
Second Intervention
| Stage | Carbon Dioxide, Then Placebo | Placebo, Then Carbon Dioxide |
|---|---|---|
| STARTED | 7 | 5 |
| COMPLETED | 7 | 5 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Excludes one patient who did not complete the second crossover intervention.
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.
| Characteristic | Unit | Entire Study Population |
|---|---|---|
| Participants analysed | 13 | |
| Age, Continuous | years | 30.69 (SD 8.13) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Diluent Challenge Contralateral Secretion Weight at Antigen Challenge, measured over 10 minutes post diluent challenge and 10 minutes post antigen challenge.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | milligrams |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the change from diluent challenge in contralateral secretion weight at antigen challenge, measured in milligrams. To collect secretions, challenge solutions were placed on disks, which were applied to the nasal septum. Filter paper disks were then placed on both sides of the septum to collect nasal secretions. Their weight change was used to measure secretion weight. The endpoint subtracts the contralateral secretion weight for the diluent challenge from that for the antigen challenge.
In general, measuring the nostril opposite the challenge site can describe a response beyond the directly challenged side. A change from a diluent challenge also distinguishes the antigen-associated response from the reference challenge response. These are measurement features; they do not by themselves establish that the endpoint predicts symptoms or treatment benefit.
The registry reports a median change of 6.0 for carbon dioxide and 19.6 for placebo. It identifies the dispersion as the full range: -3.1 to 54.1 for carbon dioxide and 0.0 to 55.2 for placebo. The endpoint description specifies measurement 10 minutes after diluent challenge and 10 minutes after antigen challenge. The record does not report a treatment-effect estimate with a confidence interval or a statistical test for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome summaries are medians of the change in contralateral secretion weight. The median is 6.0 in the carbon dioxide group and 19.6 in the placebo group. The registry reports full ranges of -3.1 to 54.1 and 0.0 to 55.2, respectively. The summaries describe the observed endpoint values; they are not estimates of uncertainty around a treatment effect.
These results should be read as descriptive group summaries rather than as a formal comparison. The registry record contains no analysis entries for the outcome, and it does not report a p-value, a confidence interval for the treatment contrast, or an adjusted analysis. The arm-level medians and ranges do not provide the paired participant-level information needed to evaluate a crossover contrast. The record also does not report period-specific or sequence-specific results. Consequently, the posted summaries cannot establish whether the observed difference is compatible with chance variation or how precisely a within-participant effect is estimated.
In general, a confidence interval describes the precision of an estimated effect under a statistical model. A full range instead describes the lowest and highest observed values in the summarized group. The reported ranges therefore should not be interpreted as confidence intervals, and they do not quantify the uncertainty in a treatment comparison. The registry identifies the endpoint dispersion as full range; it does not report a separate standard deviation or standard error for these values.
The primary endpoint is a change from diluent to antigen challenge, not a direct measure of seasonal allergic-rhinitis symptoms. The study summary presents the challenge response as a possible predictor of whether carbon dioxide might benefit seasonal allergic rhinitis. The registry record does not report a validation analysis linking the challenge response to subsequent seasonal symptoms or treatment outcomes. Thus, the endpoint results address the recorded challenge measure, not that proposed predictive relationship.
The primary endpoint population excludes one patient who did not complete the second crossover intervention. Although the endpoint summaries list 12 participants in each intervention group, the record does not explain how missing observations were handled beyond that exclusion statement. No conclusions about the direction, clinical importance, or reproducibility of a treatment effect can be drawn from the descriptive summaries alone.
9. Statistical Methods Explained
What does the median describe? The median is the middle value when observations are ordered. It describes the center of the observed endpoint values and is less influenced by extreme values than the mean. The registry reports medians for the primary outcome: 6.0 for carbon dioxide and 19.6 for placebo. It does not report a mean or another measure of central tendency for this outcome.
What does the full range describe? A full range gives the lowest and highest observed values in a group. The reported ranges are -3.1 to 54.1 for carbon dioxide and 0.0 to 55.2 for placebo. In general, a range conveys the spread of observed values but does not show how values are distributed between its endpoints. It is not a measure of precision for a treatment-effect estimate. The ranges should not be read as confidence intervals.
Why does the crossover design matter? In general, a crossover study compares interventions received by the same participants. A suitable analysis can use within-participant differences, which may reduce the influence of stable differences between people. That analysis must also account for the design and the timing of measurements. Period effects, treatment sequence, and carryover can matter if responses depend on when an intervention is given or on a prior intervention. The registry record does not report sequence, period results, washout details, or a statistical method for handling these considerations.
The posted summaries are organized by intervention and give medians and ranges. Those summaries do not show each participant’s paired responses across interventions. Without a reported paired contrast or the information needed to reconstruct one, the group summaries cannot be treated as a crossover treatment-effect estimate. It would be inappropriate to derive a new effect estimate by subtracting the reported medians: such a calculation would not recover the participant-level paired comparison, and no recalculated treatment contrast is reported.
How should uncertainty be assessed? In general, a confidence interval gives a range of values compatible with an estimated effect under the chosen model and assumptions. A p-value evaluates data against a specified null hypothesis under a statistical model. Neither is reported for the primary comparison in the registry record. The ranges describe observed outcome values, not uncertainty around a comparison. The registry also does not report a standard error, test statistic, or model specification for the primary endpoint.
What is the role of the challenge measurement? The endpoint is constructed by subtracting contralateral secretion weight for the diluent challenge from that for the antigen challenge. This change measure focuses on the response associated with the antigen challenge relative to the diluent reference. In general, using a change measure can account for a reference measurement, but interpretation still depends on how observations were collected and analyzed. The registry describes the collection procedure and measurement times, but does not report a model for the endpoint or a validation method for using it as a predictor of seasonal treatment benefit.
What does the record say about planning? The record describes a sample-size planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are general planning exercises, not observed power and not evidence that the trial was designed with those assumptions. The registry does not report the trial’s own sample-size justification or a detailed protocol statistical plan. No numerical planning estimates are reported in the registry record for this analysis.
The registry lists no analysis entries. Therefore, the posted primary summaries should not be mistaken for an inferential analysis. The statistical methods used by the sponsor, including any analysis of paired crossover data, are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five secondary outcomes, including secretion weight, histamine levels, and eosinophil influx. It reports six outcome measures. Multiple outcomes can create multiplicity concerns: in general, examining several outcomes can increase the chance of at least one apparently notable result if each is tested separately. A prespecified hierarchy or adjustment can address that issue, but the registry record does not report a multiplicity strategy, a hierarchy among outcomes, or inferential results for the secondary outcomes.
The primary endpoint population excludes one patient who did not complete the second crossover intervention. The record does not report the reason for non-completion, the missing values for other outcomes, or a general missing-data method. It does not describe whether any imputation, sensitivity analysis, or alternative analysis population was used. The primary endpoint summaries list 12 participants for each intervention, but those counts do not establish how missing data were handled across all outcomes.
The registry does not define an intention-to-treat, per-protocol, or other analysis population. It also does not report the planned statistical analysis or any interim-analysis approach. No conclusions about these procedures should be inferred from the posted summaries or the completed status of the study.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Carbon Dioxide | 0 | 12 | 0.0% |
| Placebo | 0 | 13 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Carbon Dioxide | 0 of 12 |
| Placebo | 0 of 13 |
The adverse-event record lists zero serious adverse events and zero other adverse events in the carbon dioxide group, with 12 participants at risk in each category. For placebo, it lists zero serious adverse events and zero other adverse events, with 13 participants at risk in each category. These are the recorded event counts and denominators; they should be read as registry entries, not as proof that no unrecorded events occurred.
Deaths are not reported in the registry record. The different at-risk counts for the two interventions should not be reconciled by assuming that they represent identical analysis populations or exposure periods. The record does not explain the denominator difference or provide further information about event collection, timing, severity beyond the serious/non-serious distinction, or follow-up completeness.
In general, zero events in a small study do not establish that an intervention has no safety risks. These figures describe only the adverse-event information entered in the registry, and they do not support a comparative safety conclusion on their own.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized, double-masked crossover study of nasal carbon dioxide and placebo before nasal challenge in people with allergic rhinitis. Its primary outcome is a change in contralateral secretion weight from diluent to antigen challenge. The posted medians are 6.0 for carbon dioxide and 19.6 for placebo, with full ranges of -3.1 to 54.1 and 0.0 to 55.2.
Those summaries show the recorded distributions’ central values and ranges. They do not provide a formal estimate of the within-participant treatment effect, its precision, or a test of the comparison. The registry record does not report a confidence interval or p-value for the primary outcome. Because this is a crossover study, group-level medians do not reveal how each participant’s response differed between interventions.
The study summary describes the antigen challenge response as a possible predictor of whether carbon dioxide could benefit seasonal allergic rhinitis. The primary endpoint is a nasal secretion measurement during challenge, not a direct assessment of seasonal symptoms. The registry record does not report evidence validating the challenge response as a predictor or an evaluation of seasonal treatment outcomes. The results therefore do not establish that the endpoint predicts clinical benefit.
The adverse-event entries record zero serious and zero other adverse events for both interventions, with different numbers at risk. Deaths are not reported in the registry record. These entries do not establish the absence of risk, particularly because the record does not provide further details about event ascertainment or follow-up.
Overall, the registry supports a description of the study design, endpoint, and posted outcome summaries. It does not support a conclusion about the statistical significance, precision, clinical importance, or seasonal treatment implications of the primary comparison.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and summary format matter. A crossover design can support within-participant comparisons, but interpretation depends on paired data and attention to sequence, period, and carryover. The registry reports intervention-level medians and ranges, not a paired treatment-effect estimate. Those summaries cannot show how the same participants responded under both interventions.
The endpoint also illustrates the distinction between a measured biological response and a clinically meaningful outcome. Contralateral secretion weight is defined as a change from diluent to antigen challenge. The study summary presents this challenge response as a possible predictor of seasonal benefit, but the registry record does not report validation of that relationship. A plausible surrogate or predictor requires evidence linking it to the outcome it is intended to anticipate.
Finally, the record demonstrates the limits of descriptive results without an inferential analysis. Medians and full ranges describe observed values, whereas confidence intervals and statistical tests address uncertainty in a specified comparison. No such primary comparison is reported in the registry record. The study’s results can therefore be described, but they cannot establish the precision or statistical strength of a treatment contrast from the available entries.
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 registry record does not report a detailed statistical analysis plan, the method used to analyze the crossover design, or a formal primary comparison. It provides no primary-outcome confidence interval or p-value. The posted medians and full ranges do not convey the paired responses needed to assess a within-participant contrast or its precision.
Important crossover details are also not reported, including intervention sequence, period-specific results, and washout arrangements. Without these details, the record does not permit assessment of potential period or carryover effects. The primary endpoint excludes one patient who did not complete the second crossover intervention, but the reason for non-completion and broader missing-data procedures are not reported in the registry record.
The registry frames the antigen challenge response as a possible predictor of benefit in seasonal allergic rhinitis, but it does not report validation of that predictive relationship or seasonal symptom outcomes. The primary measurement is a challenge-related secretion-weight change, so it should not be treated as a direct measure of seasonal benefit.
Safety entries show zero reported serious and other adverse events, but the record gives different at-risk counts for the interventions and does not explain the difference. Deaths are not reported in the registry record. Further details about event ascertainment and follow-up are not reported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Intranasal CO2 for Allergic Rhinitis — NCT00618410.
- Registry record last updated 2014-01-27; status last verified 2013-12.
- Results first posted 2014-01-27.
- 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.
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18. Record Summary
The registry record describes a completed, randomized, double-masked crossover study sponsored by the University of Chicago, with enrollment listed as 13. The study compared nasal carbon dioxide, USP, with nasal placebo, each administered 30 minutes before nasal challenge. The recorded phase is NA.
The primary endpoint was the change in contralateral secretion weight from diluent to antigen challenge, measured in milligrams. The reported medians were 6.0 for carbon dioxide and 19.6 for placebo; the full ranges were -3.1 to 54.1 and 0.0 to 55.2. One patient who did not complete the second crossover intervention was excluded from the primary endpoint.
The record lists five secondary outcomes and reports no analysis entries. It does not report a formal primary comparison, a confidence interval, or a p-value. Serious and other adverse-event counts are recorded as zero in both groups; deaths are not reported in the registry record.