Effects of Roflumilast on Insulin and Blood Sugar Levels in Prediabetic Overweight and Obese Individuals: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Roflumilast on Insulin and Blood Sugar Levels in Prediabetic Overweight and Obese Individuals (NCT01862029), a na phase 1, phase 2 study. The primary outcome is Change in Insulin Sensitivity- Pre-roflumilast.

2. Clinical Question

3. Trial Design

This completed study is recorded as a phase 1 and phase 2, single-group trial of roflumilast. The registry lists enrollment as 24. Allocation is marked not applicable, masking is listed as none, and the model is single group. These features mean the registry record does not describe a randomized, masked comparison between roflumilast and a control intervention. It also does not provide a like-for-like control group from which to estimate a treatment contrast.

The brief summary describes a study lasting approximately 8 weeks, with approximately five visits over about 7 weeks, including two overnight inpatient stays. It describes screening with a physical exam and medical history, collection of blood and urine samples, and a 3-day diet and exercise assessment. A special diet and inpatient testing are also described. The summary mentions blood sugar tests and body scans during an inpatient stay. The available description ends while discussing possible tissue sampling, so further procedure details are not reported in the registry record.

The recorded start date is 2013-05-22, and the primary completion date is 2017-07-25. The study status is completed. These administrative details do not establish when each participant was treated or how long each person contributed outcome data. Participant-level follow-up, adherence, withdrawals, and the analysis population are not reported in the registry record.

The registry identifies roflumilast as the intervention, but the arm description is empty. Dose, administration instructions, treatment duration by participant, and concomitant care are not reported in the registry record. The design can describe measurements made during a treatment study, but without a concurrent comparator it cannot isolate a treatment effect from other explanations for any observed change.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Among the 14 subjects who met the inclusion criteria, 3 subjects withdrew participation prior to starting the study procedures due to expected possibility of noncompliance with the protocol schedule. Two additional subjects were withdrawn for new medical findings prior to their initiation of the study medication.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects who underwent the clamp procedure at time point: pre- roflumilast

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 Insulin Sensitivity- Pre-roflumilast, measured over Baseline.

The primary outcome is titled “Change in Insulin Sensitivity- Pre-roflumilast.” Its description says that peripheral insulin sensitivity was assessed using the M value from a hyperinsulinemic euglycemic clamp performed before participants began roflumilast. The recorded timeframe is Baseline, and the specified unit is mg/grams Fat Free Mass/minute. The outcome is defined as a mean with standard error as its dispersion measure.

A hyperinsulinemic euglycemic clamp is a method for assessing how the body responds to insulin while blood glucose is maintained at a controlled level. In general, the M value is used as a measure of insulin-stimulated glucose disposal; a higher value represents greater glucose disposal under the clamp conditions. This general description does not supply a result for this study.

The endpoint wording and description do not align perfectly: the title uses the word “Change,” whereas the description identifies a pre-treatment measurement and the timeframe is Baseline. The record does not state a second measurement or a change calculation for this primary outcome. No mean, standard error, confidence interval, or test result for the endpoint is reported in the registry record. Consequently, the recorded information establishes the intended measurement and its units, but not the magnitude, direction, or precision of any treatment-period change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods need to be interpreted in light of the design and the information actually reported. This study is recorded as single group, with allocation not applicable and no masking. In general, a single-group study can describe the measurements observed among its participants. Without a concurrent control group, however, it cannot directly compare outcomes under roflumilast with outcomes under an alternative condition. Changes over time could reflect treatment, natural variation, measurement conditions, or other influences. The registry record does not report an analysis designed to separate these explanations.

What does the primary measure represent?

The stated primary measure is the clamp M value, with the unit mg/grams Fat Free Mass/minute. The outcome description identifies a pre-roflumilast measurement and the timeframe is Baseline. The result type is a mean, with standard error as the stated measure of dispersion. In general, a mean summarizes the average observed measurement in an analysis group. A standard error describes the precision of an estimated mean, rather than the spread of individual participants’ measurements. A standard deviation, which is not specified as the endpoint’s dispersion measure, describes participant-to-participant spread.

The term “Change” in the endpoint title could suggest a comparison over time, but the description specifies a pre-treatment M value. The registry record does not define a post-treatment value, a change score, or the model used to estimate any change. It would therefore be inappropriate to treat the baseline measurement as a reported treatment response. No mean, standard error, confidence interval, or statistical test for the primary outcome is reported in the registry record.

How should precision be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the statistical model and stated confidence level. A narrow interval indicates greater precision than a wide interval, though interpretation also depends on the endpoint and design. A p-value, in general, describes how unusual the data would be under a specified null hypothesis and model; it is not the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record.

The endpoint’s stated standard error could help quantify uncertainty in its mean if the numerical mean and standard error were available. Those values are not reported. In addition, the analysis count for the clamp endpoint is not reported in the registry record. Although enrollment is listed as 24, the primary outcome population is defined as participants who underwent the clamp at the pre-roflumilast time point. These counts need not be identical.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. These are assumptions for hypothetical sample-size planning, not features of the recorded single-group design. The registry record does not provide the resulting planning counts or the observed effect used to generate them. No new sample-size value or effect estimate can therefore be interpreted from this information.

In general, a planning calculation asks how many participants a hypothetical design might require to detect an assumed effect under specified conditions. It is not a measure of the probability that this completed study detected an effect, and it is not observed power. The planning setup refers to two equally allocated arms, whereas the trial is recorded as single group. That difference means the illustration should not be mistaken for the trial’s actual allocation or analysis.

What can be inferred from the safety counts?

The record reports adverse-event counts for a group titled “Subjects Who Took Roflumilast.” Nine participants are listed at risk for serious adverse events and nine for other adverse events. Serious adverse events are recorded for zero participants, other adverse events for six, and deaths for zero. These figures are descriptive. The record does not provide event-level detail, follow-up time for each person, or a control group for comparison.

Methods for comparing groups, adjusting for baseline differences, handling repeated measurements, or controlling false-positive findings across multiple outcomes are not described in the registry record. The record lists two outcome measures and zero analyses. The specific statistical model, analysis population, missing-data approach, and any prespecified decision thresholds are not reported in the registry record. Without those details and numerical outcome results, statistical significance and precision for the primary question cannot be assessed.

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("Pre-roflumilast")
n   <- c(7)
m   <- c(48.7)
sp  <- c(10.4)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Pre-roflumilast  7  48.700  27.516  23.252  74.148

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns the risk of false-positive findings when several outcomes, time points, subgroups, or statistical tests are considered. In general, prespecifying a primary outcome and an analysis strategy can help make findings easier to interpret, while adjustments or other controls may be used when multiple inferences are planned. The registry record lists two outcome measures and zero analyses, but does not report a multiplicity strategy, a hierarchy of outcomes beyond identifying the primary outcome, or whether any adjustment was planned. It is therefore not possible to determine how multiple comparisons were handled.

The primary outcome population is described as participants who underwent the clamp procedure at the pre-roflumilast time point. The number analyzed for that endpoint is not reported in the registry record. Although enrollment is 24, the record does not establish that every enrolled participant contributed to each outcome. The numbers screened, treated, completing follow-up, and included in each analysis are not reported in the registry record.

Missing-data methods are also not reported in the registry record. There is no description of how missing measurements, incomplete visits, withdrawals, or unavailable clamp results were handled, nor is there a reported comparison of participants with and without outcome data. In general, missingness can affect an estimate if the availability of measurements is related to participants’ characteristics or outcomes. Without counts and methods, the extent and possible impact of missing data cannot be assessed.

The record does not identify an intention-to-treat, per-protocol, or other analysis population. It also does not report an interim-analysis plan, stopping rules, or a statistical analysis plan. These details should not be inferred from the phase designation or study completion status. The absence of a reported method is not evidence that no method was used; it means the registry record does not document it.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event figures are reported for a group titled “Subjects Who Took Roflumilast.” Nine participants are listed as at risk for serious adverse events, with zero affected. Nine participants are listed as at risk for other adverse events, with six affected. Deaths are recorded as zero. These are counts, not estimates comparing roflumilast with another treatment or with no treatment.

The safety denominator of nine is distinct from the enrollment figure of 24. The registry record does not explain why the at-risk group is smaller than the enrollment total, whether all participants received treatment, or whether the at-risk count reflects a particular safety follow-up period. It also does not report the types of other adverse events, their severity, timing, duration, or whether participants experienced more than one event. The count of six affected participants should not be read as six total events.

In general, the absence of recorded serious adverse events in a group does not establish that an intervention has no serious risks. Small or incompletely followed groups can provide limited information about uncommon events, and these counts have no concurrent control group for context. The figures describe what the registry reports; they do not establish causality or comparative safety.

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

The study addresses an important measurement question: how insulin sensitivity and metabolic parameters are assessed in overweight or obese individuals with elevated blood sugar during a roflumilast study. Its primary measure is described as the pre-treatment clamp M value, reported in mg/grams Fat Free Mass/minute. The record also indicates that roflumilast was the intervention and that the study was completed.

The available record does not report the numerical primary outcome or a treatment-period change. It therefore does not show whether the mean M value increased, decreased, or remained similar over time, nor does it quantify uncertainty around such a change. The title’s use of “Change” does not substitute for a reported follow-up measurement or change estimate. The outcome description identifies a baseline measure, and that distinction limits what can be concluded.

The single-group design is also central to interpretation. Even if measurements at multiple times were available, a within-group change alone would not establish that roflumilast caused the change. Without a concurrent control group, other explanations cannot be ruled out through a direct treatment comparison. The registry record does not report an adjusted comparative analysis.

The safety counts describe zero serious adverse events and zero deaths among nine participants at risk, and other adverse events in six participants at risk. They do not establish comparative risk, and the record does not give event-level details. These counts should be read as limited descriptive information rather than as a complete assessment of safety.

Accordingly, the record supports a description of the research question, study structure, intended primary measurement, and reported adverse-event counts. It does not support a numerical claim about the primary result, a conclusion about treatment efficacy, or a causal claim. Missing numerical results and analysis details prevent assessment of the endpoint’s size, precision, statistical significance, and robustness.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why the design, endpoint definition, and reported results must be read together. The registry identifies a specific physiological measurement: the clamp M value for peripheral insulin sensitivity, in a defined unit and at baseline. That specificity helps clarify what the investigators intended to measure. At the same time, the endpoint title refers to “Change,” while its description and timeframe identify a pre-roflumilast baseline measure. This makes the distinction between a measurement and a treatment-period change especially important.

The single-group design also illustrates the difference between describing observations and estimating a comparative treatment effect. A group’s measurements can be summarized, but without a concurrent control group there is no direct estimate of what would have happened under another condition. This is a design limitation, not a statistical technique that can be resolved merely by reporting a p-value.

Enrollment of 24 and an endpoint population defined by clamp participation show why analysis denominators matter. The record does not state how many participants contributed to the primary endpoint, while the safety figures identify nine participants at risk. Clear reporting of the number assessed, number analyzed, and handling of missing measurements is important for judging the scope and precision of findings.

The posted safety counts also demonstrate the limits of descriptive event totals without event details or a comparison group. Finally, planning assumptions based on an observed effect do not amount to observed power or evidence that a study detected an effect. As the registry record does not report outcome estimates or the results of those planning illustrations, readers cannot evaluate the numerical result or its precision. The statistical lesson is to distinguish the stated research aim from the evidence actually reported.

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.

Several limitations specific to this study affect interpretation. First, it is recorded as a single-group study, with no masking and allocation not applicable. There is no concurrent control group for a direct comparison. As a result, the design cannot distinguish a treatment-associated change from other influences on measurements over time.

Second, the primary endpoint description is ambiguous for change assessment. Its title includes “Change,” but the description says the M value was obtained before roflumilast began, and its timeframe is Baseline. The registry record does not report a post-treatment primary measurement, a change estimate, or an analysis contrasting time points. This prevents interpretation of the primary endpoint as a documented treatment response.

Third, the primary outcome result is not reported in the registry record. No mean, standard error, confidence interval, or p-value is available for interpretation. The record also does not report the number analyzed for the clamp endpoint, missing-data handling, or the analysis population beyond stating that participants underwent the baseline clamp.

Fourth, enrollment of 24 should not be confused with the number contributing to each outcome. The safety group lists nine participants at risk, but the registry record does not explain the denominator difference or provide participant flow. The types and timing of other adverse events are not reported, limiting safety interpretation.

Finally, the registry record does not report the dose and schedule, detailed statistical plan, multiplicity approach, or specific analysis methods. The phase designation and completed status do not fill those gaps. Together, these reporting and design limitations constrain assessment of treatment effects, statistical precision, and generalizability beyond the described population.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of Roflumilast on Insulin and Blood Sugar Levels in Prediabetic Overweight and Obese Individuals — NCT01862029.
• Registry record last updated 2018-09-04; status last verified 2018-02-26.
• Results first posted 2018-09-04.
• 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

The registry record describes a completed phase 1 and phase 2, single-group study of roflumilast in overweight or obese individuals with elevated blood sugar. Enrollment was 24; the recorded start date is 2013-05-22 and the primary completion date is 2017-07-25. The brief summary describes a study lasting approximately 8 weeks.

The primary outcome concerns peripheral insulin sensitivity measured by the clamp M value before roflumilast, with a stated unit of mg/grams Fat Free Mass/minute and mean with standard error. Despite the outcome title’s reference to “Change,” numerical primary results are not reported in the registry record. The number analyzed for that endpoint and the statistical analysis methods are also not reported.

For safety, nine participants were listed at risk for serious adverse events and nine for other adverse events. Serious adverse events and deaths were recorded for zero participants; other adverse events were recorded for six. The record does not provide event-level details or a comparison group. These findings are descriptive and do not establish a comparative treatment effect.