The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients (NCT02496780), a randomized phase 2, phase 3 study. The primary outcome is Change From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients.

2. Clinical Question

The registry title describes the intended focus as insulin therapy and protein turnover in pre-diabetic cystic fibrosis patients. The rationale in the record discusses insulin’s potential anabolic effect and the possibility of influencing protein catabolism, undernutrition, and clinical deterioration. Those statements describe the rationale, not a demonstrated trial result. The posted outcome data address change in an intermediate biological measure over a short period. They do not, by themselves, establish what happened to nutrition, symptoms, morbidity, mortality, or longer-term health.

The question is narrower than whether insulin is beneficial overall. It asks about a specific measure, in a specific population, over 4 weeks, with placebo as the comparison. The registry record does not report a result for the stated combined-insulin primary analysis, so interpretation must distinguish that planned contrast from the available Novolog–placebo estimate. The Levemir group’s mean change is posted, but a corresponding comparison estimate is not reported in the registry record.

3. Trial Design

The registry describes a randomized, triple-masked, parallel trial with Phase 2 and Phase 3 designations. Enrollment is listed as 65. The sponsor is the University of Minnesota. The study began in 2015-08, had primary completion in 2022-07, and is listed as terminated. These registry entries describe the trial’s organization and status; they do not explain why the study was terminated.

Three intervention groups appear in the primary outcome data: placebo, basal insulin Levemir, and rapid-acting insulin Novolog. Placebo was described as an injectable insulin diluent given once or three times daily. Levemir was described as once-daily basal insulin, and Novolog as rapid-acting insulin taken before meals three times daily. The separate healthy-control group was matched by age, gender, and BMI to cystic fibrosis participants, but was used only for baseline information. The record says that no intervention or outcome measure was collected from healthy controls.

The primary outcome is change from baseline in endogenous protein breakdown after 4 weeks. The record describes a two-step comparison approach: first combine both insulin types and compare them with placebo, then compare the two insulin types separately with one another and with placebo. The posted primary data include an unadjusted Novolog–placebo comparison and group-level results for all three treatment arms. A result for the combined-insulin contrast is not reported in the registry record. Nor is a separate Levemir–placebo comparison estimate reported there.

The primary outcome groups contain 11.0 placebo participants, 9.0 Levemir participants, and 10.0 Novolog participants. These are the counts associated with the posted outcome values, not the enrollment figure for the whole trial. The registry record does not report how participants moved from total enrollment into each analysis group, or whether all randomized participants contributed primary outcome data. The original sample-size justification, allocation procedures beyond randomization, masking procedures, and reasons for termination 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Healthy controls did not participant in the primary aim

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 From Baseline in Endogenous Protein Breakdown (Flux) After 4 Weeks of Insulin/Placebo Therapy, CF Patients, measured over 4 weeks.

The primary endpoint is change from baseline in endogenous protein breakdown, expressed as flux, after 4 weeks of insulin or placebo therapy in cystic fibrosis patients. The registry describes the measure as a rate and gives its unit as µmol/kg(LBM)/min. It was determined from a stable isotope-labelled test meal. The posted arm values are means of a continuous measure, with dispersion reported as standard error.

Protein breakdown is one aspect of protein turnover. Measuring change from baseline focuses on how the rate differs after the study period compared with the pre-treatment measurement, rather than only comparing post-treatment levels. The record’s rationale connects protein catabolism with undernutrition and clinical deterioration, but the endpoint itself remains a physiological measurement. A change in this measure is not automatically equivalent to a change in nutritional status, symptoms, or longer-term clinical outcomes.

The endpoint was selected to assess a biological effect over 4 weeks, while placebo provides a comparison for changes that might occur without active insulin assignment. The healthy controls are not part of this treatment comparison: they were used for baseline information only and did not participate in the primary aim. A distinction also matters between the stated analysis plan and the result available for review. The record describes an initial combined-insulin comparison, but a posted estimate for that contrast is not reported in the registry record. The available inferential comparison is rapid-acting Novolog versus placebo.

The registry does not report additional details about the test-meal protocol, the timing of measurements, or the exact construction of the change score. Those details should not be inferred from the endpoint name alone.

7. Results Posted in the Registry

• Rapid-acting Insulin Novolog: mean 0.00 versus -0.01 on control; difference 0.01 (95% CI -0.14 to 0.16), standardized effect d = 0.06; z-test p = 0.891.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • CF Total: mean 0.96 versus 0.92 on control; difference 0.04 (95% CI -0.46 to 0.55), standardized effect d = 0.05; z-test p = 0.870.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CF Total and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists one secondary outcome: baseline protein turnover in cystic fibrosis participants compared with healthy controls. The available data describe a cross-sectional baseline contrast rather than a response to treatment. The mean difference is positive, the confidence interval includes zero, and the unadjusted p-value is 0.87. The result is therefore imprecise and does not establish a clear baseline separation between the groups.

This endpoint relates to the primary question by providing baseline context for protein turnover in cystic fibrosis participants relative to healthy controls. It does not estimate the effect of insulin, because the healthy-control group did not receive an intervention and did not contribute to the primary aim. Nor can the baseline contrast confirm or refute a change after 4 weeks. The primary outcome asks about within-treatment-period change in cystic fibrosis patients, while this secondary outcome asks about a difference between populations at baseline.

Only one secondary outcome is listed, and no reported analyses are listed for it. As with the primary result, the available comparison is a simple unadjusted recalculation from posted summary statistics. The registry record does not report further secondary analyses or adjustments for other variables.

Unadjusted secondary results generally carry less weight than a prespecified primary contrast because they may be exploratory and may be interpreted among multiple comparisons. If several outcomes or contrasts are examined, some findings can appear notable by chance alone. The registry record does not report whether multiplicity procedures were planned or used. Here, the baseline comparison is best treated as descriptive context, not as confirmatory evidence about insulin treatment.

The overall pattern across the posted outcome information is limited: the primary endpoint addresses a treatment-related change, while the secondary endpoint addresses baseline group differences. Neither should be substituted for the other. The baseline result cannot fill the gap left by the absence of a posted result for the combined-insulin primary comparison, and it does not supply evidence about longer-term clinical outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Baseline Protein Turnover (Flux), CF Patients vs Healthy Controls

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s measure is expressed on a numerical scale, and the registry reports group means and standard errors. A mean describes the average value in a group. It does not describe every participant, and it can conceal variation or unusual observations. The standard error describes the uncertainty in an estimated mean; it is not the same as the standard deviation, which describes variation among individual measurements.

What does a mean difference describe?

A mean difference compares the average change in one group with the average change in another. For the posted Novolog–placebo comparison, the estimate is based on the group mean changes. A positive estimate means that the Novolog group’s mean change is higher than the placebo group’s mean change on the outcome scale. The estimate alone does not tell how precisely that contrast is known. Precision is assessed with its confidence interval, and compatibility with a null difference is also commonly described using a p-value.

The comparison is an unadjusted calculation from the posted summary statistics. “Unadjusted” means that the estimate is not reported as controlling for other variables or for a more elaborate analysis structure. The registry record does not report a sponsor analysis for the primary outcome, so the available recalculation should be read as a simple comparison rather than as a substitute for an analysis plan or a full participant-level analysis. The discrepancy flag is false; no discrepancy with a sponsor result is identified.

How should the confidence interval and p-value be read?

A confidence interval gives a range of effect estimates compatible with the data under the calculation’s assumptions. It conveys uncertainty around the estimated difference. The Novolog–placebo interval includes zero and extends to both negative and positive values. That breadth means that the data are compatible with more than one direction of difference, as well as with little or no difference. It does not mean that all values in the interval are equally likely, nor does it prove that the true difference is zero.

The p-value of 0.891 is an unadjusted test statistic. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A large p-value is not proof of no effect, particularly when the estimate is imprecise. Interpretation should combine the estimate, its interval, design context, and the limitations of the available analysis.

Why does the reported dispersion matter?

The arm-level dispersion is reported as standard error, not standard deviation. Standard error reflects uncertainty in a group mean and generally depends on both variability in individual observations and the number of observations. It should not be read as the range in which most individuals’ results fall. Since the group counts are limited, standard errors and confidence intervals are important reminders that a mean can be unstable. The registry record does not provide individual data or standard deviations for the primary endpoint.

The pooled standard deviation and standardized effect size used in the recalculated comparison are derived from the summary data. They can express a mean difference relative to an estimate of variability, but they do not add independent clinical information. The standardized effect is not a treatment outcome, and its interpretation depends on the measurement and the variability estimate. It should not be confused with an observed clinical benefit.

What do randomization and masking contribute?

Randomization is intended, in general, to create treatment groups that are comparable on average at assignment, including with respect to factors that may not be measured. Triple masking indicates that the registry identifies the study as masked at three levels, but the identities of those masked are not reported in the registry record. The details of allocation generation, concealment, and how masking was maintained are also not reported. Those implementation details matter when assessing how well a randomized design was carried out.

A parallel design means that the registry identifies participants as being assigned to groups that run alongside one another, rather than describing a crossover. The primary outcome is compared across treatment groups after 4 weeks. The record does not report further detail on the schedule of assessments or whether the analysis accounted for baseline values beyond defining the endpoint as change from baseline.

What is not documented about the analysis?

The record describes an initial combined-insulin comparison and later separate comparisons, but it does not report the result for the combined comparison. It also does not report the sponsor’s statistical analysis, covariate adjustments, handling of missing measurements, analysis population definitions, or whether an intention-to-treat approach was used. The number of reported analyses is listed as zero. This does not establish that no analysis was performed; it means that reported analyses are not listed in the registry record.

The study includes multiple groups, outcomes, and described contrasts. If many hypotheses are tested, the chance of at least one apparently notable result can increase. General methods for controlling multiplicity include adjusting significance thresholds or identifying a primary contrast in advance. Whether any such procedures were used for this trial is not reported in the registry record. The posted p-values are unadjusted and should be interpreted in that context.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data identify the effect being estimated. For the Novolog–placebo comparison, the confidence interval is wide and includes zero, extending to both negative and positive differences. That pattern indicates substantial uncertainty in the direction and size of the contrast. The point estimate is only one location within that range; it should not be read as a precise description of the underlying effect.

A confidence interval is not a guarantee that the true effect lies inside its endpoints. In general, it is a range produced by a method that would cover the true parameter at a stated rate over repeated samples if the method’s assumptions held. Its practical value is that it displays the scale of uncertainty more fully than the point estimate or p-value alone. The record does not provide a confidence level in the outcome text, but the posted comparison interval is available for interpretation.

The primary outcome groups are small: 11.0 participants in placebo, 9.0 in Levemir, and 10.0 in Novolog. The standard errors are similar in scale across these groups, but the sample counts remain limited. Small groups can make estimates sensitive to individual observations and leave broad uncertainty. Individual participant data are not reported, so the influence of particular measurements cannot be assessed.

The posted confidence interval and p-value are unadjusted calculations based on the summary statistics. No discrepancy with a sponsor analysis is identified, but the registry record does not list a sponsor analysis to compare against. The available precision therefore pertains to the posted simple contrast, not to the unreported combined-insulin primary contrast or a separately estimated Levemir comparison.

Precision is distinct from clinical importance. Even a precise estimate would require context about what magnitude of change matters for patients, and that threshold is not reported in the registry record. Conversely, an imprecise estimate does not prove that no important difference exists. It means the posted data leave a broad range of possibilities unresolved.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s own original design assumptions; those original assumptions are not reported in the registry record. The calculation uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect.

For the Novolog–placebo contrast, planning for 100% of the observed effect corresponds to 4,332 participants per arm for 80% power and 5,799 participants per arm for 90% power. Planning for 75% of the observed effect corresponds to 7,700 participants per arm for 80% power and 10,308 participants per arm for 90% power. Planning for 50% of the observed effect corresponds to 17,325 participants per arm for 80% power and 23,193 participants per arm for 90% power.

The 80% power column describes the number of participants per arm that the stated calculation estimates would be needed for an 80% chance of detecting the chosen effect under the assumptions. The 90% column describes the corresponding planning target for a 90% chance. These are design calculations for future planning, not statements about the chance that the observed result is true. They are not observed power.

The smaller-effect scenarios require more participants because a smaller separation between group means is harder to distinguish from random variation. A curve that traces these assumptions should be read in the same way: moving toward a smaller effect target means that the required number of participants rises. The inputs are particularly uncertain because they use the observed effect from a small outcome comparison. If the observed estimate is unstable, planning numbers derived from it may also be unstable.

There are also planning illustrations for the baseline comparison of cystic fibrosis participants with healthy controls. They use the same stated assumptions and likewise express participants per arm. Those calculations do not represent a treatment comparison and should not be interpreted as the original trial’s enrollment target. Neither set of calculations explains the trial’s actual enrollment or the reason the posted primary groups are smaller than total enrollment.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.010; pooled standard deviation σ = 0.173.
2. n = 2 × (1.96 + 0.842)² × 0.173² / 0.010² = 4,331.0, rounded up to 4,332 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.0104                      # observed difference in means
sigma <- 0.172747153225078                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2496780)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 4,332 (80% power), 5,799 (90% power)
 75% of observed effect: n per arm = 7,700 (80% power), 10,308 (90% power)
 50% of observed effect: n per arm = 17,325 (80% power), 23,193 (90% power)
power.t.test: 4332 
Simulated power at n = 4,332 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The primary outcome description sets out more than one contrast: an initial comparison combining both insulin types against placebo, followed by separate comparisons involving each insulin type. The record also lists a baseline secondary outcome comparing cystic fibrosis participants with healthy controls. Multiple outcomes and contrasts can create multiplicity: the more statistical tests considered, the greater the chance that at least one result appears noteworthy by chance. The record does not report whether any multiplicity adjustment, hierarchy, or other control of multiple testing was planned or used. The posted p-values are unadjusted.

The registry record describes the combined-insulin comparison as the first primary analysis, but does not report its estimate. It also does not report a separate Levemir comparison estimate. The available Novolog–placebo estimate is therefore only part of the analysis strategy described for the primary endpoint. The record lists no reported analyses. That listing does not show whether analyses were conducted outside the registry record; it indicates that results of such analyses are not reported there.

Missing-data handling is not reported in the registry record. It is not stated how missing baseline or follow-up measurements were treated, whether participants were excluded from an analysis, or how any incomplete measurements affected the outcome groups. The participant counts attached to the primary outcomes are smaller than overall enrollment, but the record does not explain the difference. It would be inappropriate to assume that the difference reflects withdrawal, missing endpoint data, eligibility, or any particular reason.

The analysis population is also not defined in the posted results. The record does not say whether the primary analysis followed assignment regardless of treatment received, included only participants who completed treatment, or used another rule. Details about adherence, protocol deviations, and exclusions are not reported. These omissions limit assessment of how the randomized groups contributed to the outcome comparison.

The original sample-size justification, the planned statistical model, interim analyses, and the prespecified handling of multiplicity are not reported in the registry record. The planning illustrations based on the observed effect do not fill that gap: they are not evidence of the assumptions used to design the trial. The trial is listed as terminated, but a reason and any consequences for analysis completeness are not reported.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry’s adverse-event summary lists zero participants with serious adverse events in each group: placebo, basal insulin Levemir, rapid-acting insulin Novolog, and healthy controls. It also lists zero deaths in every group. These are counts among the participants listed as at risk in the adverse-event record. The serious-event terms list is empty, so no specific serious adverse-event terms are reported in the registry record.

The summary separately lists participants affected by other adverse events: 2 in placebo, 4 in Levemir, 4 in Novolog, and 5 among healthy controls. The registry does not provide event terms or further descriptions for these counts. The healthy-control group is described as being used for baseline information only, with no intervention or outcome measure collected; its presence in the adverse-event summary does not make it part of the treatment comparison.

These counts describe what is posted, not the probability of harm for an individual or a comparison adjusted for differences in exposure. The record does not give event timing, duration, severity for the other events, or detail about how events were collected. Zero reported serious events should be read as zero recorded in this summary, not as proof that serious events are impossible or that risks are absent.

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

The main numerical result is an imprecise Novolog–placebo comparison for change in endogenous protein breakdown after 4 weeks. The point estimate is positive, but its confidence interval includes zero and spans negative and positive differences. The unadjusted p-value is 0.891. These results do not provide a precise estimate of the direction or size of a difference. They also do not prove that the treatments produce the same change or that a difference of clinical importance is absent.

The endpoint is a measure of protein turnover, not a direct measure of nutrition, symptoms, lung function, quality of life, morbidity, or mortality. The registry rationale mentions possible links between protein catabolism, undernutrition, and clinical deterioration, but the posted data do not establish those links or show whether the measured changes affected clinical status. The trial’s short endpoint timeframe is 4 weeks; longer-term outcomes are not reported in the registry record.

The outcome record includes mean changes for three treatment groups, but only a Novolog–placebo comparison estimate is posted. Although the primary description says both insulin groups were to be combined for an initial comparison with placebo, the result for that combined contrast is not reported in the registry record. The Levemir group’s mean change is posted, but a separate inferential comparison is not. As a result, the available estimate should not be treated as a complete answer to every comparison described in the primary endpoint text.

The secondary baseline comparison with healthy controls provides context, not evidence about treatment response. It cannot show whether insulin altered protein turnover because the healthy-control group did not receive intervention and did not participate in the primary aim. Its unadjusted result is also uncertain.

Finally, enrollment of 65 does not mean that 65 participants contributed to the primary outcome comparison. The outcome groups are smaller, and the reason is not reported in the registry record. The record also does not report missing-data methods, analysis populations, or the reason the trial was terminated. These gaps limit what can be inferred about completeness and robustness. The sound conclusion is descriptive: the posted estimates are uncertain and do not settle the treatment question or establish effects on broader clinical outcomes.

17. Why This Trial Matters Statistically

This trial is statistically instructive because the registry sets out a primary analysis strategy that is not fully represented in the posted comparison results. The outcome description calls for combining both insulin types against placebo, followed by separate comparisons. The available inferential result is for rapid-acting Novolog versus placebo. Keeping the stated analysis strategy distinct from the comparison actually reported is essential when describing what the evidence addresses.

The example also illustrates why a point estimate should not be read alone. The Novolog–placebo estimate has a wide confidence interval that includes zero, and the unadjusted p-value is 0.891. The interval communicates substantial uncertainty; the p-value does not establish equivalence or absence of an effect. A careful interpretation describes the range of uncertainty without converting a non-significant result into proof of no difference.

Small outcome groups are another important feature. The primary endpoint counts are 11.0, 9.0, and 10.0 across the three treatment arms. Such counts can leave estimates sensitive to individual observations and limit precision. Total enrollment of 65 does not remove that limitation when the posted outcome groups are smaller and the reason for the difference is not reported.

The record also distinguishes a biological measure from a clinical outcome. Protein breakdown may be relevant to the study rationale, but the posted endpoint alone cannot demonstrate a change in health status. Similarly, baseline comparisons with healthy controls should not be confused with randomized treatment contrasts. Finally, planning calculations based on the observed effect are illustrative rather than evidence of original design assumptions or achieved power. These distinctions help keep conclusions proportional to what the registry actually reports.

18. 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 outcome groups are small, and the posted comparison is imprecise. Total enrollment is 65, but the primary outcome counts are 11.0 for placebo, 9.0 for Levemir, and 10.0 for Novolog. The reason these counts do not account for the full enrollment is not reported in the registry record. No participant-level results are available to assess outliers, distributions, or the influence of individual observations.

The primary endpoint description includes a combined-insulin comparison, but the registry record does not report its result. A separate Levemir comparison estimate is also not reported. This leaves the posted Novolog–placebo contrast as an incomplete representation of the described analysis strategy. The record lists no reported analyses, so it is not possible to assess whether the displayed recalculation matches a fuller sponsor analysis or a prespecified model.

Details of missing-data handling, analysis populations, adherence, exclusions, and protocol deviations are not reported. The registry status is terminated, but the reason and its effect on enrollment, follow-up, or analysis are not reported. The original sample-size justification, any interim analyses, and the planned statistical analysis are also not reported. Planning figures based on the observed effect cannot be used to reconstruct those decisions.

The endpoint is a short-term physiological measure assessed after 4 weeks. It does not directly report nutritional or broader clinical outcomes, and longer follow-up results are not reported in the registry record. The registry’s rationale discusses potential clinical relevance, but the posted endpoint does not establish changes in morbidity, mortality, or overall status. Finally, the safety summary lacks detailed event descriptions and timing, limiting interpretation of the other adverse-event counts.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: The Impact of Insulin Therapy on Protein Turnover in Pre-Diabetic Cystic Fibrosis Patients — NCT02496780.
• Registry record last updated 2025-03-17; status last verified 2025-03.
• Results first posted 2025-03-17.
• 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.

22. Record Summary

The registry describes a randomized, triple-masked, parallel trial with Phase 2 and Phase 3 designations, sponsored by the University of Minnesota. Enrollment is 65, the study began in 2015-08, primary completion was in 2022-07, and its status is terminated.

The primary endpoint is change from baseline in endogenous protein breakdown after 4 weeks, measured using a stable isotope-labelled test meal. The posted primary comparison is rapid-acting Novolog versus placebo. Its confidence interval spans zero, and its unadjusted p-value is 0.891, indicating substantial uncertainty rather than a precise estimate of the difference. The result for the described combined-insulin comparison is not reported in the registry record.

A secondary outcome compares baseline protein turnover in cystic fibrosis participants and healthy controls. The record also lists adverse-event counts, including zero serious adverse events and zero deaths in all groups. Analysis details, reasons for termination, and explanations for the smaller primary outcome groups are not reported in the registry record.