Mesalamine to Reduce T Cell Activation in HIV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mesalamine to Reduce T Cell Activation in HIV Infection (NCT01090102), a randomized phase 4 study. The primary outcome is Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, double-blind, crossover study, with mesalamine and placebo as the two interventions. The sequences were Mesalamine Then Placebo and Placebo Then Mesalamine. Enrollment was 33. The study is listed as completed, with a start date of 2010-06 and primary completion in 2012-12. It is a Phase 4 study sponsored by the University of California, San Francisco.

A crossover design assigns participants to treatment sequences rather than comparing two groups that remain on separate treatments throughout. Each sequence begins with a different intervention, after which the sequence switches to the other intervention. For the primary endpoint in this study, the stated timeframe is Week 0 to Week 12 and the title specifies the first 12 weeks of study. The primary comparison therefore concerns the initial treatment period, before the sequence switch. The registry record does not report details about any washout period or the timing and handling of later-period measurements.

The primary outcome is a continuous measure: log(10) change in the percentage of activated CD8+ T cells, identified by CD38+HLA-DR+. The record reports a mean and a 95% confidence interval for each sequence. It also reports a two-sided t-test for the comparison. One participant assigned to begin with mesalamine withdrew without receiving the allocated intervention and was excluded from the primary analysis. The record does not describe additional analysis-population definitions or how other missing measurements were handled.

The sequence-specific group sizes reported for the primary outcome are 14 for Mesalamine Then Placebo and 18 for Placebo Then Mesalamine. These are analysis counts for the reported outcome, not a complete account of all participants' follow-up. Details of randomization procedures, masking implementation, treatment adherence, and crossover-period 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 12 Weeks

Reasons for not completing this period:

Second 12 Weeks

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 1 participant assigned to first receive Mesalamine was excluded from analysis due to having withdrawn participation without receiving the allocated 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.

6. Primary Endpoint

The registry lists the primary outcome as Log(10) Change in % Activated (CD38+HLA-DR+)CD8+ T Cells During the First 12 Weeks of Study, measured over Week 0, Week 12.

The primary endpoint is the log(10) change in the percentage of activated CD8+ T cells during the first 12 weeks of study. Activation is identified using the markers CD38+HLA-DR+ on CD8+ T cells. The registry describes the unit as Log10(percentage of T cells) and gives Week 0 and Week 12 as the timeframe. The outcome is continuous, and the reported summary is a mean with a 95% confidence interval for each randomized sequence.

In general, immune activation measures can be used to examine biological activity relevant to a study's research question. Here, the endpoint operationalizes the question of whether mesalamine, added to standard HIV treatment, is associated with a change in systemic immune activation during the initial treatment period. The registry's objective also discusses inflammation and possible immune-system recovery, but this primary endpoint is specifically a measure of activated CD8+ T cells. It is not itself a direct measure of symptoms, HIV disease progression, or broader clinical benefit.

The logarithmic scale represents change on a transformed scale rather than a raw percentage-point change. In general, a log transformation can make a distribution's scale more suitable for analysis when values vary multiplicatively. The record does not explain the transformation's rationale or provide a raw-scale version of the primary outcome. As a result, the reported means and confidence intervals should be read in the stated log(10) units, not interpreted as direct percentage-point changes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry summarizes it with a mean and 95% confidence interval in each sequence. A mean describes the arithmetic average on the measurement scale. Here the measurement scale is log(10) change in the percentage of activated CD8+ T cells. The mean is a group-level summary: it does not indicate that every participant had a change close to that value, and it does not describe the range of individual responses.

What does the confidence interval describe?

In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. The registry reports 95% confidence intervals for the mean in each sequence. Those intervals are not intervals containing a specified proportion of individual participants, and they do not by themselves estimate the uncertainty around the difference between the sequences. The record does not provide a confidence interval for a comparative effect.

The two reported intervals concern separate group means. It is tempting to infer a treatment comparison by looking at whether such intervals overlap, but interval overlap is not itself the reported hypothesis test. The record gives a separate two-sided t-test for the comparison. In general, a t-test evaluates a contrast in means relative to its estimated variability, subject to the assumptions of the test. Its two-sided form considers departures in either direction rather than specifying only an increase or only a decrease.

How should the reported p-value be read?

The sponsor-reported p-value is 0.63. In general, a p-value is calculated under a null hypothesis and a statistical model. It measures how unusual a test result at least as extreme as the observed result would be if that null hypothesis and model were appropriate. It is not the probability that the treatment has no effect, and it does not establish that the two sequence means are equal. It also does not measure the magnitude or importance of a difference. Interpretation should consider the point estimates, uncertainty, endpoint definition, and analysis population alongside the p-value.

The registry identifies the method as a two-sided t-test but does not report further details of its implementation, including any adjustments or specific variance assumptions. The record does not report a model that combines measurements across both crossover periods. Accordingly, the posted primary analysis is best understood as the reported comparison for the first 12 weeks, not as a complete account of treatment effects across the entire crossover.

Why does the crossover design matter?

In general, a crossover trial assigns participants to a sequence of interventions, with each participant scheduled to receive both interventions. This can allow within-participant comparisons, because measurements from the same participant may be more alike than measurements from different participants. Such an analysis needs to account for the sequence, period, and possible carryover of an earlier intervention. The primary endpoint is explicitly limited to the first 12 weeks, so the posted primary comparison uses the initial assigned treatment period rather than a within-participant contrast across both treatments.

That first-period comparison has a parallel-group structure: the sequences begin on different interventions, and the outcome is summarized by sequence at the end of the stated initial period. This description follows from the design and endpoint timing. The registry record does not report the detailed statistical model or whether later-period data were analyzed in a separate crossover model. It also does not report a washout period or details that would allow assessment of possible carryover.

What does the log transformation imply?

The endpoint is explicitly expressed as log(10) change in the percentage of activated cells. In general, transformations change the scale on which a quantity is analyzed and summarized. A mean on a log scale is a mean of transformed values, not the same quantity as a mean raw percentage-point change. The confidence intervals are likewise on the stated scale. The registry does not report a conversion back to the raw scale, so interpretations should preserve the log(10) scale rather than translating the values into an unreported raw-scale effect.

Over-dispersion is a general issue when observed variability exceeds what a chosen statistical model expects. In such settings, model-based standard errors and tests may understate uncertainty if the extra variability is not accounted for. The registry record does not report a variance assessment or a model designed to address over-dispersion. Because the primary method is identified only as a t-test, the available record does not support further conclusions about variance diagnostics or robustness analyses.

What can the posted analysis establish?

The reported analysis estimates sequence-specific average changes and provides a two-sided test of the primary comparison. It does not, by itself, establish causation beyond the randomized comparison as analyzed, quantify a clinical effect, or resolve uncertainty about other endpoints. A statistically non-small p-value is not proof of no effect, just as a small p-value would not by itself establish clinical importance. In general, precision, study design, endpoint relevance, missing data, and the complete set of analyses matter when interpreting trial results.

The registry record does not report a sample-size justification, target power, interim analyses, or a prespecified statistical analysis plan. It is therefore not possible to assess from the record whether the study was designed to detect a particular effect size or how multiple analyses were planned. Sample-size planning is conceptually distinct from observed power: planning calculations describe what a future design might need under assumptions, while observed data and their uncertainty describe the trial that was conducted. No unreported planning target or power should be inferred from the outcome summaries.

10. Analyses Reported by the Sponsor

The registry reports the sponsor's analysis as a two-sided t-test with p = 0.63. It does not give a comparative mean estimate or a confidence interval for the contrast in the available primary outcome details. The two sequence-specific means and their 95% confidence intervals are reported separately, so they can describe each group's average change but cannot be substituted for a direct interval estimate of the between-sequence effect.

No discrepancy between a sponsor analysis and a recalculated result is identified in the record. A separately recalculated comparative estimate and confidence interval are not reported in the registry record. The most direct inferential result available is therefore the sponsor-reported test, interpreted alongside the posted group summaries. The p-value does not quantify the size of a difference, and its value does not prove that the treatments are equivalent. Any interpretation should remain limited to the first-12-week primary endpoint and the analysis reported.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one secondary outcome, concerning log(10) change in the percentage of activated CD8+ T cells after treatment crossover. It also lists two outcome measures and two analyses. The available record does not provide results for that secondary outcome in the registry record for this analysis, nor does it describe a complete hierarchy of primary and secondary hypotheses.

When a study evaluates multiple outcomes or performs multiple analyses, the chance of obtaining at least one apparently noteworthy result can increase. In general, multiplicity procedures can control error rates across a defined family of tests, or an analysis plan can prioritize outcomes and state which results are confirmatory. The registry record does not report a multiplicity adjustment, an outcome hierarchy, or whether the reported p-value should be interpreted as adjusted or unadjusted. No correction should therefore be assumed.

For the primary analysis, the record states that one participant assigned to begin with mesalamine withdrew without receiving the allocated intervention and was excluded. The reported primary group sizes are 14 and 18. These details indicate that the primary analysis did not include every enrolled participant as described by the enrollment count. The registry does not report an intention-to-treat analysis, a per-protocol definition, or a sensitivity analysis addressing the withdrawal.

Other missing-data details are not reported in the registry record. In particular, the available description does not state how missing Week 0 or Week 12 measurements were handled, whether any further participants lacked outcome data, or whether imputation was used. Missingness can affect interpretation if the availability of measurements is related to treatment or outcome. Without details on the reasons for missing measurements and the analysis choices, the extent of any such influence cannot be assessed.

The record also does not report a detailed analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of prespecification, the intended analysis population, and how the multiplicity of endpoints was considered. They do not show that particular procedures were or were not used; those details are simply not reported in the registry record.

12. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (3.4%).

The adverse-event summaries report serious adverse events affecting 1 participant in the Mesalamine group, with 31 at risk, and 1 participant in the Placebo group, with 29 at risk. Other adverse events affected 2 participants in the Mesalamine group and 0 in the Placebo group, using the same respective at-risk counts. These are descriptive counts in the registry record and should be read with the group denominators shown, rather than as comparative safety estimates.

The record also lists Death among the top serious-event terms, with 3.4%. The death counts themselves are not reported in the registry record. The listed term and percentage cannot be reconciled with participant-level details from the information available, and the percentage should not be converted into a count or attributed to a particular group. The record does not provide event narratives, timing, severity breakdowns, or a causal assessment of whether events were related to treatment.

In general, adverse-event summaries describe events observed and recorded during a study; they do not on their own establish that an intervention caused an event. Differences in exposure and observation, as well as the small reported counts, constrain interpretation. These figures are not a substitute for detailed safety reporting and do not support a broad conclusion about comparative safety.

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

The primary result describes average change in a specific immune-activation measure during the first 12 weeks among participants assigned to begin with mesalamine or placebo. The mean estimates and their 95% confidence intervals show uncertainty around each sequence-specific average. The sponsor's two-sided t-test reports p = 0.63. Together, these results do not provide strong statistical evidence of a difference in the primary outcome under the reported first-period analysis.

That interpretation is narrower than saying that mesalamine has no effect. A p-value of 0.63 does not establish equivalence, and the record does not report an equivalence margin or a non-inferiority analysis. The absence of a reported comparative confidence interval also means the precision of the between-sequence contrast cannot be read directly from the registry result. The group intervals quantify uncertainty in the group means, not the treatment contrast.

The endpoint is a transformed measure of activated CD8+ T cells. It does not directly measure all systemic inflammation, immune recovery, clinical symptoms, or HIV-related outcomes. Although the study objective discusses inflammation and possible immunologic benefit, the primary result should not be taken as a result for every part of that broader objective. Nor does the posted primary comparison establish what happened after crossover; the primary endpoint timeframe is the first 12 weeks.

The study enrolled 33 participants, and the registry reports an exclusion from the primary analysis after withdrawal before receiving the allocated intervention. The available record does not give a full account of missing outcome data, analysis populations, or the detailed crossover-period analysis. Those limitations mean the reported primary estimates should be interpreted as the results of the posted analysis, not as a complete description of every participant or every scheduled outcome.

In general, trial interpretation depends on the estimate, its uncertainty, the endpoint's relevance, the design, and the completeness of reporting. Here, the available evidence supports a restrained description: the reported group summaries and test do not show a clear difference in the specified first-period endpoint, while leaving uncertainty about the magnitude of any underlying difference and about outcomes not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates how the estimand—the specific effect a study aims to describe—depends on the design and endpoint timing. Although the trial is a crossover, the primary endpoint is limited to the first 12 weeks. The reported primary comparison is therefore between randomized sequences at the start of treatment, not a comparison that combines both treatment periods within participants. Recognizing that distinction prevents the crossover label from being mistaken for a within-participant primary analysis.

It also highlights the value of distinguishing group means from a comparative effect. The registry gives a mean and confidence interval for each sequence and a p-value for the test. Those summaries answer related but different questions: the means describe average change within each sequence, while the test addresses a comparison. A direct effect estimate and confidence interval for that comparison would make its magnitude and precision easier to assess, but such an estimate is not reported in the registry record.

The endpoint is biologically focused and transformed onto a log(10) scale. That makes it important to retain the stated scale when describing the results and not translate them into raw percentage changes without a reported conversion. The study objective reaches beyond the endpoint to inflammation and potential immune-system recovery, underscoring the need to distinguish a measured biomarker from broader clinical questions.

Finally, the record shows why outcome reporting and missing-data details matter. It identifies a withdrawal before intervention and an exclusion from the primary analysis, but gives limited information about other missing measurements, multiplicity, and the analysis plan. These are not reasons to dismiss the reported result; they are boundaries on how confidently readers can assess its precision, generalizability, and relationship to other trial questions.

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 primary endpoint concerns a biomarker, not a direct clinical outcome. It measures log(10) change in the percentage of activated CD8+ T cells, and the registry record does not report a raw-scale conversion. The result consequently addresses a specific immune-activation measure rather than the full set of outcomes suggested by the study objective, including systemic inflammation or immune-system recovery.

The primary comparison is restricted to the first 12 weeks, although the design is crossover. The record does not report details of the later-period analysis, a washout period, or how possible period or carryover effects were addressed. Conclusions from the primary result therefore should not be extended to a combined analysis of both treatment periods.

One participant assigned to begin with mesalamine withdrew without receiving the allocated intervention and was excluded from the primary analysis. The record does not describe other missing data, the full analysis population, or sensitivity analyses. The reported group sizes may be understood as the analyzed counts, but the available information does not explain all differences between enrollment and outcome analysis.

The registry reports sequence-specific confidence intervals and a two-sided t-test p-value, but does not report a comparative effect estimate with its confidence interval. It also does not report a sample-size justification, interim analyses, detailed statistical analysis plan, or multiplicity procedures. These reporting gaps constrain assessment of prespecification, precision of the treatment contrast, and interpretation across outcomes. They do not establish that procedures were absent; those details are not reported in the registry record.

The adverse-event information is also limited. It gives counts and at-risk denominators, lists Death with a percentage among the serious-event terms, and does not report death counts or event-level details. Causal attribution, timing, and the clinical context of these events cannot be determined from the summary alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Mesalamine to Reduce T Cell Activation in HIV Infection — NCT01090102.
• Registry record last updated 2014-08-13; status last verified 2014-08.
• Results first posted 2014-08-11.
• 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

This completed Phase 4 study was a randomized, double-blind crossover trial of mesalamine and placebo in HIV infection, sponsored by the University of California, San Francisco. Enrollment was 33. The primary endpoint was log(10) change in the percentage of activated CD8+ T cells during the first 12 weeks.

The registry reports mean changes of 0.03 (95% confidence interval -0.14 to 0.2) for Mesalamine Then Placebo and -0.01 (95% confidence interval -0.1 to 0.07) for Placebo Then Mesalamine. The sponsor-reported two-sided t-test p-value was 0.63. One participant assigned to begin with mesalamine withdrew before receiving the intervention and was excluded from the primary analysis.

The result is limited to the posted primary endpoint and first treatment period. Further details about missing data, crossover-period analysis, multiplicity, and the statistical plan are not reported in the registry record.