Ictal and Interictal Inflammatory Markers in Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ictal and Interictal Inflammatory Markers in Migraine (NCT01138150), a randomized phase 4 study. The primary outcome is Change in the Total Serum Adiponectin (T-ADP).

2. Clinical Question

The scientific premise in the registry is that inflammatory proteins in blood might be higher during an acute migraine attack than during a pain-free period. The study description says the investigators planned to evaluate blood levels during an attack and compare them with pain-free levels. The posted primary outcome is narrower: it reports changes in total serum adiponectin after treatment, separated by response status and time point. The registry does not provide a posted pain-free comparison within these primary results.

That distinction matters for interpreting the question. The results describe mean changes within two response-status groups at several times. They do not directly estimate the difference between the randomized Treximet and placebo groups, nor do they establish that response status itself caused a change in adiponectin. The record does not report the formal statistical test for a between-group contrast. Therefore the posted means and intervals should be read as descriptive estimates of change in the reported groups, rather than as a demonstrated treatment effect.

3. Trial Design

The registry identifies this as a phase 4, randomized, triple-masked, parallel study of people with migraine. It records enrollment of 36 participants and a completed status. The record lists a start in 2009-09 and primary completion in 2013-06. These dates describe the registry record; they do not by themselves specify when each participant was enrolled, treated or followed.

The listed interventions are Treximet and placebo. The arm descriptions say that participants were randomized to receive Treximet or placebo during an acute migraine attack. The Treximet description identifies the drug as sumatriptan and naproxen. Blood collection was intended to assess immune and inflammatory markers, including adipocytokines and cytokines, as well as sex hormones. The primary outcome names measurements 30, 60 and 120 minutes after treatment. The placebo description also refers to repeated blood draws after presentation, including these time points.

The registry’s narrative arm descriptions refer to fourteen participants in each randomized arm, while the posted primary outcome rows report n=17 for each response-status group. The safety record also lists 17 participants at risk in each intervention group. The record does not explain the differing counts or how the response-status groups relate to the randomized arms. In particular, the primary result rows are titled as treatment responders and non-responders; they are not labeled as the randomized Treximet and placebo arms. These groups should not be silently treated as interchangeable.

A parallel randomized design ordinarily assigns participants to separate intervention groups. Masking indicates that the study was registered as triple-masked, but which individuals were masked and how masking was implemented are not reported in the registry record. Further details about allocation procedures, eligibility criteria, treatment adherence and follow-up are not reported in the registry record. The registry lists seven secondary outcomes, including several adiponectin measures, leptin and resistin. The registered primary results concern total serum adiponectin change by response status and time.

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

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 Change in the Total Serum Adiponectin (T-ADP), measured over 30 minutes after treatment, 60 minutes after treatment, 120 minutes after treatment.

The primary endpoint is change in total serum adiponectin (T-ADP), measured in ug/mL. Adiponectin is one of the proteins that the study sought to measure as an inflammatory marker. The registry frames the broader biological question around whether blood levels of inflammatory proteins differ during an acute migraine attack and when pain free. For the primary outcome, the reported measure is the mean change after treatment, classified by treatment response and assessed at 30, 60 and 120 minutes.

Using change focuses the endpoint on how a measured level shifts over the stated period, rather than on a single blood concentration alone. Repeated time points can describe whether the estimated change varies over the early post-treatment period. The endpoint is continuous: its values can take a range of numerical amounts, and the record reports means with 95% confidence intervals.

The registry does not report the precise reference measurement used to define the change, the operational definition of a responder, or whether changes were calculated from a baseline sample for each participant. Those details are important to reproduce or fully assess the endpoint. They are not reported in the registry record, so interpretation should remain limited to the stated mean changes by response group and time point. The endpoint is a laboratory measurement; by itself it does not describe symptom relief, clinical benefit or the causal effect of one randomized intervention compared with the other.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports a mean and 95% confidence interval for each listed response group and time point. These summaries describe the estimated average change and the uncertainty around that estimate. A mean is sensitive to the values contributing to it, and it does not show the full distribution of individual measurements. The registry does not report standard deviations, medians, individual observations or a distributional plot in the information used for this interpretation.

What a confidence interval conveys

In general, a confidence interval is a range generated by a statistical procedure to express uncertainty about an estimated quantity. A narrower interval indicates greater precision under that procedure, while a wider interval indicates less precision. A 95% confidence interval is not a guarantee that a particular interval contains the true value, nor does it give the probability that the true value lies within the observed interval. Its interpretation depends on the assumptions and method used to construct it.

For responders, the three reported intervals are entirely negative. For non-responders, the reported intervals extend across zero. That observation concerns each group’s mean change relative to zero. It is not equivalent to a test comparing the groups. To assess a difference between groups, an analysis would need to estimate that contrast and its uncertainty, taking account of the study design and repeated measurements. Such a contrast and its method are not reported in the registry record. Overlap or non-overlap of separate confidence intervals is not a substitute for the confidence interval or test for the difference itself.

Repeated measurements and response groups

The outcome includes measurements at multiple post-treatment times. In general, measurements from the same participant are related rather than independent. Analyses of repeated observations can account for that within-participant relationship, for example by modeling time and participant-level correlation. The record does not report whether the primary analysis used a repeated-measures model, separate time-specific analyses, or another approach. It also does not report whether baseline values or other covariates were included.

The reported group labels are responders and non-responders. In general, response status is a grouping variable, not necessarily a randomized assignment. Randomization to an intervention supports certain comparisons between assigned groups when the analysis preserves that assignment; a comparison based on a post-treatment response category has a different interpretation. The registry does not describe the responder definition or how participants were categorized, so the status groups cannot be interpreted as randomized treatment arms. No causal claim about response status follows from the displayed means alone.

Analysis choices that are not documented

The registry identifies the outcome as a mean with 95% confidence intervals, but the specific estimator, standard error calculation, model, hypothesis test and confidence-interval construction are not reported in the registry record. It does not state whether the analysis followed randomized assignment, whether any participants were excluded, or how missing measurements were handled. These omissions prevent an independent assessment of whether the uncertainty estimates reflect the design and available data.

There are several reported outcomes: the primary adiponectin measure and seven listed secondary outcomes, covering additional adiponectin forms and other markers. In general, testing several outcomes or time points can increase the chance of at least one apparently notable result when each is examined separately. A prespecified hierarchy or multiplicity adjustment can address that issue, but neither is described in the registry record. No adjustment should be presumed. The posted result provides no p-value for the primary estimates, and no formal comparison should be inferred from the confidence intervals alone.

The registry states the primary outcome’s three time points, but does not identify a single time point as the sole primary contrast or explain how the repeated times were incorporated into the analysis. It also does not report a sample-size justification, an interim analysis plan, a stopping rule, or a detailed statistical analysis plan. Those items are not reported in the registry record. Without them, the precision and analysis choices can be described from the posted summaries, but the original planned inferential framework cannot be reconstructed.

Reading the estimates in context

The values are reported to two decimal places and should be read at that precision. The confidence intervals express uncertainty in group means, not the range of changes among individual participants. They also do not capture every source of uncertainty, such as uncertainty arising from measurement choices, missing data or unreported analysis decisions. In general, biological measurements can vary within and between people; the record does not provide enough information to characterize that variation.

Finally, the registry lists a randomized parallel trial but reports this endpoint by response category. The distinction between the design’s randomized assignment and the result’s grouping is central. The reported estimates are useful as descriptive summaries of the posted outcome, but a direct randomized treatment effect, its precision and the statistical evidence for a treatment contrast are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome assessed at 30, 60 and 120 minutes, and seven secondary outcomes. In general, examining multiple outcomes and time points creates a multiplicity issue: when many estimates or tests are considered, some may appear noteworthy by chance even if there is no underlying effect. A prespecified primary contrast, testing hierarchy or statistical adjustment can help define how multiple comparisons are interpreted. Such a strategy is not reported in the registry record. The primary result rows do not include p-values or a reported test across time points, so no multiplicity adjustment can be assumed.

Missing-data handling is also not reported in the registry record. The outcome is based on blood measurements at repeated time points, but the record does not state whether every participant contributed a measurement at each time, how incomplete measurements were treated, or whether any participants were excluded from the analysis. The n=17 listed for each result row does not establish that all randomized participants had complete observations or that the same analysis population was used at every time.

The registry does not identify an intention-to-treat population, a per-protocol population, or another analysis set for the primary endpoint. It also does not explain the relationship between the randomized Treximet and placebo groups, the response-status categories, the enrollment of 36 and the reported n=17 values. These gaps make it difficult to assess whether the posted results represent all randomized participants and how missing observations might affect the estimates.

The record does not report a prespecified statistical analysis plan or a sample-size justification. Consequently, it is not possible to determine from the registry whether the displayed groupings and time-point analyses were specified in advance or how the investigators planned to address multiple testing and incomplete measurements. The absence of these details is a limitation in interpretation, not evidence that any particular analysis choice was made.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The safety record lists Treximet and Sugar Pill groups, with 17 participants at risk in each. It reports zero serious adverse events and zero other adverse events for each group. These are the posted event counts for the groups and categories shown. The record does not list any serious adverse-event terms.

These figures should be interpreted as registry-reported counts, not as proof that no adverse events occurred outside the definitions, observation period or reporting process used for the record. The registry information presented does not describe how adverse events were collected, the duration of safety follow-up, or the criteria used to classify events as serious or other. The adverse-event counts therefore cannot be used to compare event rates over an unreported follow-up period or to assess events not captured in the record.

Death counts are not reported in the registry record. The blank death fields should not be read as zero deaths. The figures are also separate from the primary adiponectin outcome and do not resolve the mismatch between the narrative arm descriptions and the group sizes listed for safety and outcome results. They are limited safety summaries, with the reporting detail needed for broader interpretation not reported in the registry record.

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

The posted results show negative estimated mean changes in total serum adiponectin among treatment responders at 30, 60 and 120 minutes after treatment. The corresponding 95% confidence intervals are entirely below zero. Among non-responders, the estimated mean changes are positive at the reported times, but each confidence interval extends across zero and includes both negative and positive values. These summaries describe the direction and precision of the recorded group means.

They do not demonstrate that the responder and non-responder groups differ statistically. No direct estimate or test of that contrast is reported. They also do not establish a Treximet-versus-placebo effect: the primary results are labeled by response status, and the record does not explain how those categories correspond to randomized assignment. A difference in group means cannot be attributed to treatment without an appropriate comparison and documented analysis.

The result is a laboratory outcome, not a direct measure of migraine symptoms or patient experience. The broader study description concerns inflammatory markers during migraine and pain-free periods, but the posted primary results report changes after treatment by response status. The record does not provide a pain-free comparison in these primary result rows. Nor does it provide enough information to determine the clinical meaning of a particular change in ug/mL.

The confidence intervals communicate uncertainty in the mean estimates but do not describe the range of individual responses. The non-responder intervals are wide enough to encompass changes in either direction, while the responder intervals are on the negative side of zero. Neither pattern alone determines the biological mechanism, the cause of response status, or the effect of randomized assignment.

The registry does not report the responder definition, detailed analysis plan, missing-data approach or reconciliation of enrollment and reported group counts. Those omissions constrain what can be concluded from the posted numbers. The defensible interpretation is therefore descriptive: the record reports different directions of mean change by response-status label, with notably different interval positions, but does not report the comparison needed to establish a between-group or treatment effect.

13. Why This Trial Matters Statistically

This study illustrates why the labels attached to a result matter as much as the design label attached to a trial. The registry records randomized assignment to Treximet or placebo, yet the primary results are presented for treatment responders and non-responders. Randomized groups and response-status groups answer different statistical questions. The former can support a comparison by assigned intervention; the latter may describe patterns among participants classified after treatment. Without knowing how response was defined and how those categories relate to assignment, the estimates cannot be read as a randomized treatment contrast.

The record also makes precision visible. The responder mean-change intervals lie below zero at each listed time, while the non-responder intervals span zero and extend in both directions. This provides a useful example of why a point estimate alone is incomplete: uncertainty affects how confidently the direction and size of a mean change can be described. At the same time, confidence intervals for separate groups do not replace an interval for the difference between them.

Repeated laboratory measurements raise further design and analysis questions. Observations at several times from the same participants are generally related, and multiple outcomes can complicate interpretation. The registry does not specify how those features were modeled or how multiplicity was addressed. Recognizing the distinction between what is reported and what remains undocumented is an important part of statistical reading.

Finally, the enrollment figure, narrative arm counts and reported result counts do not align transparently in the record. Rather than resolving that discrepancy by assumption, a careful reader should recognize it as a constraint on understanding participant flow and analysis populations. This trial is statistically instructive because its posted summaries invite careful separation of descriptive patterns, randomized comparisons, precision and missing methodological detail.

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 define treatment response, even though the primary results are divided into responders and non-responders. Without an operational definition, the classification cannot be reproduced or evaluated, and it is unclear when the classification was determined relative to the outcome measurements. The record also does not explain how these categories relate to assignment to Treximet or placebo.

Participant counts are not reconciled. The study enrollment is 36; the narrative arm descriptions refer to fourteen participants randomized to each intervention; and the result rows and safety groups list 17. The record does not explain these differences, the number analyzed for each outcome or any participant flow. This prevents a clear account of how many randomized participants contributed to the primary estimates.

The primary endpoint description does not specify the reference value used to calculate change, the exact measurement procedures, or how observations at the several time points were analyzed together. Standard deviations and individual data are not reported in the posted primary results. The analysis model, confidence-interval method, covariate adjustment, missing-data handling and analysis population are also not reported in the registry record.

Although seven secondary outcomes are listed and the primary outcome has multiple time points, the record does not describe a multiplicity strategy or identify a complete statistical analysis plan. It does not report a sample-size justification or interim analysis plan. The limited safety summary does not give follow-up duration or detailed event-collection procedures, and death counts are not reported in the registry record. Together, these reporting gaps limit reproducibility and restrict interpretation to the posted descriptive estimates and event counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ictal and Interictal Inflammatory Markers in Migraine — NCT01138150.
• Registry record last updated 2016-10-06; status last verified 2016-08.
• Results first posted 2016-10-06.
• 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 describes a completed phase 4 randomized, triple-masked, parallel study of migraine, with enrollment of 36. The listed interventions are Treximet and placebo. The study description concerns blood markers during acute migraine, while the primary outcome is mean change in total serum adiponectin after treatment at 30, 60 and 120 minutes.

Primary results are reported for treatment responders and non-responders, with n=17 in each row and 95% confidence intervals. The responder estimates are negative at all three time points; non-responder estimates are positive, with intervals spanning zero. The registry does not report a direct randomized treatment comparison or a formal test between response-status groups.

The registry also lists seven secondary outcomes and reports zero serious and zero other adverse events in each of the two safety groups, each listed as 17 at risk. Death counts are not reported in the registry record. The record does not reconcile its enrollment, narrative arm counts and reported result counts, or provide several details needed to assess the analysis, including the response definition, missing-data approach and statistical plan.