Effect of Intranasal Insulin on LH Concentrations in Man: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Intranasal Insulin on LH Concentrations in Man (NCT02154477), a randomized phase 1, phase 2 study. The primary outcome is LH.

2. Clinical Question

This is a question about a short-term hormone measurement, not a question about longer-term clinical outcomes. The trial focuses on whether the measured LH concentration changes under the two visit conditions. The registry summary gives a biological rationale involving insulin in the brain and glands that release sex hormones, but that rationale is not evidence of an observed effect in this trial.

3. Trial Design

The registry describes NCT02154477 as a randomized, double-masked crossover trial with Phase 1 and Phase 2 designations. Its status is completed, and the recorded enrollment is 14. The sponsor is Texas Tech University Health Sciences Center. The record lists intranasal insulin and placebo (intranasal saline) as the interventions.

A crossover design means that participants receive more than one study condition at different visits, so each participant can contribute measurements under both conditions. Here, the arm descriptions say that all patients receive insulin at one visit and saline at another. This allows the comparison to be made within participants, which can help account for stable differences between people. It also means that the order and timing of visits can matter when interpreting the comparison.

The registry identifies randomization and double masking, but does not report how the treatment order was generated, who was masked, whether masking was assessed, or how the interval between visits was selected. Details of the insulin dose and saline administration are also not reported in the registry record. These omissions limit the ability to assess how the design was implemented.

The record labels adverse-event groups Diabetes and Control. Those labels should not be read as proof of how the primary endpoint groups were constituted: the intervention descriptions state that all patients received both insulin and saline, while the endpoint description says it was measured in both arms. The registry does not clarify the relationship between these group labels and the crossover comparison. It also does not report a rationale for the enrollment target or whether recruitment followed an original sample-size plan.

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: diabetes

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 LH, measured over 4 hours.

The primary endpoint is LH concentration, measured in IU/L, with the outcome parameter described as a mean and dispersion described as a standard deviation. The stated timeframe is 4 hours. LH is a hormone involved in reproductive endocrine signaling, and the registry summary identifies it as the hormone whose release the trial sought to assess after intranasal insulin compared with intranasal saline.

A continuous endpoint such as hormone concentration retains information about the measured level rather than reducing the result to a yes-or-no event. A mean describes the central value across observations, while a standard deviation describes how spread out those observations are around the mean. In general, both are useful for understanding the pattern of measurements, although neither alone establishes how precisely a treatment contrast has been estimated.

The registry record does not give the mean LH concentration or standard deviation for either condition, nor does it report a numerical contrast, confidence interval, or test result. It therefore does not allow readers to assess the direction, magnitude, or precision of the primary endpoint comparison. The listed 4 hours timeframe describes when the endpoint was assessed; it does not establish whether any difference persisted beyond that measurement window.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why use a crossover design?

In general, a crossover trial compares conditions within the same participants across separate visits. This can reduce the influence of stable participant characteristics on the comparison, because each person serves as their own comparator. The registry describes this trial as a randomized, double-masked crossover and says patients received insulin at one visit and saline at another. It does not report the sequence of those visits or the interval between them.

Measurements from the same person are generally correlated. A suitable analysis should account for this dependence rather than treating each visit measurement as unrelated. The statistical method used for the LH endpoint is not reported in the registry record. The record also does not say whether period, sequence, or carryover effects were assessed. These are design considerations in general, not claims about what was done in this trial.

What do mean and standard deviation describe?

The endpoint is a continuous measure, with the mean specified as the summary parameter and standard deviation as the dispersion measure. In general, the mean gives a central summary of the measured values. The standard deviation describes how much individual measurements vary around that mean. A mean and standard deviation can help describe a group of observations, but a treatment comparison also needs an estimate of the contrast and information about its precision.

For a crossover comparison, the distribution of within-participant differences may be important. Separate means and standard deviations for each condition do not by themselves reveal the variability of paired differences, because the association between a participant's measurements across visits also matters. The registry record reports neither condition-specific summaries nor paired-difference summaries. Therefore, a numerical comparison cannot be reconstructed from the posted information.

How should precision be understood?

In general, a confidence interval expresses uncertainty around an estimated effect under a statistical model. It gives a range of values compatible with the observed data and the assumptions used to calculate it. Its width reflects precision: greater uncertainty tends to produce a wider interval. A confidence interval is not reported for the primary LH comparison, so its precision cannot be assessed from the registry record.

A hypothesis test and a confidence interval answer related but different questions. A p-value measures how unusual the data would be under a specified null hypothesis and model. It does not quantify the size or importance of an effect. Neither a p-value nor a test result for the primary endpoint is reported. A statistically significant finding, if one were reported, would not by itself show that a difference is important in clinical terms; interpretation would also require the effect estimate and relevant context.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability exceeds what a chosen statistical model expects. It is especially relevant to count outcomes, where a simple model may assume a particular relationship between the mean and variance. The LH outcome is described as a continuous measure, not a count. The registry does not report an analysis model or a diagnostic assessment of variability, so no claim about over-dispersion or its handling can be made for this endpoint. More generally, a model that understates variability can make uncertainty appear smaller than it is, while an appropriate model should reflect the data structure and observed variation.

What do the planning assumptions mean?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. These are planning assumptions, not a statement of the trial's own protocol or original design. The registry does not report the protocol's sample-size justification or confirm that these assumptions were used to choose enrollment.

In general, a sample-size calculation estimates how much information a future study may need for a chosen effect size and statistical assumptions. It is not a measure of the probability that the completed study found a true effect. In particular, a sample-size illustration should not be called observed power. The planning values are not reproduced in this explanation; they should be read as hypothetical planning quantities, not as observed results or proof of adequate precision.

The registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report how the outcome categories were analyzed or which comparison, if any, was designated for inference. This prevents assessment of the statistical model, the handling of repeated measurements, and the relation between any analysis and the stated primary question.

10. Multiplicity, Missing Data and Analysis Populations

The registry states that the primary outcome has several categories or time points and was not reduced to one comparison. It lists one outcome measure and zero analyses. The statistical plan for selecting or combining time points and categories, and any method for controlling multiplicity, are not reported in the registry record.

In general, multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. If many comparisons are tested, the chance of finding an apparently unusual result can increase unless the analysis plan accounts for that. This is a general concern, not a claim that a particular unreported analysis was conducted in this trial. Because the record does not give a selected primary contrast or its numerical result, the implications of multiplicity for inference cannot be evaluated.

The record does not report whether any LH measurements were missing, how missing measurements were handled, or whether participants who did not complete both visits were included in an analysis. It also does not describe an analysis population, such as an intention-to-treat or per-protocol population. Enrollment of 14 does not establish how many participants contributed to the endpoint analysis.

These omissions matter in a crossover design because a within-participant comparison depends on measurements from both conditions. In general, missing one visit can affect whether a participant contributes a paired comparison. The registry does not report whether this occurred or how it was addressed. Without the analysis population, missing-data account, and prespecified statistical approach, readers cannot assess the potential impact of incomplete outcome information or the robustness of any primary-endpoint inference.

11. 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.

The adverse-event record lists Diabetes and Control as separate groups. For Diabetes, the serious adverse-event count is 0 among 8 at risk, and the other adverse-event count is 0 among 8 at risk. For Control, the serious adverse-event count is 0 among 6 at risk, and the other adverse-event count is 0 among 6 at risk. Deaths are recorded as 0 in each group. No serious adverse-event terms are listed.

These are registry counts for the groups as labeled; they are not results for the LH endpoint. The crossover descriptions say patients received insulin at one visit and saline at another, but the record does not explain how the Diabetes and Control safety groups relate to the treatment conditions or to each participant's exposure. The adverse-event reporting period and event definitions are not reported in the registry record.

In general, a recorded count of zero means that no event was recorded in that category for the stated group and reporting. It does not establish that an intervention is free of risk, particularly when the record does not detail the observation period or ascertainment process. The safety figures should therefore be read as the posted counts, not as a comprehensive estimate of safety.

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

This completed randomized, double-masked crossover trial was designed to compare LH concentrations after intranasal insulin with concentrations after intranasal saline in men described in the registry summary as obese, diabetic, and having hypogonadotropic hypogonadism. The endpoint was a mean concentration in IU/L measured over a 4 hours timeframe. The record identifies a short-term hormone measurement as the primary question.

The posted record does not report numerical LH results or a statistical comparison. It therefore does not show whether measured concentrations were higher, lower, or similar between the conditions, nor how precisely any difference was estimated. No conclusion about the presence or absence of an effect on LH can be drawn from the registry entry as posted. The biological rationale in the summary is context for the study question, not a substitute for outcome data.

Even if an endpoint comparison were available, a short-term LH measurement would not by itself establish a longer-term effect on hormone function or a clinical outcome. The 4 hours timeframe defines the recorded endpoint window. The registry does not report outcomes beyond that window or results for other clinical measures.

Likewise, the adverse-event counts are limited to the categories and groups reported in the record. They do not establish that no unrecorded events occurred or provide a complete characterization of risk. The group labels and the relation of those safety figures to the crossover exposure are not clarified.

The central limitation for interpretation is the absence of primary outcome results and analysis details. Enrollment, design labels, and safety counts describe aspects of the study record, but they cannot replace the treatment contrast, its uncertainty, and the analysis population. The record supports describing the research question and design; it does not support a conclusion about the observed LH response.

13. Why This Trial Matters Statistically

This trial is statistically notable because its crossover structure makes the participant, rather than an independent group of participants, central to the treatment comparison. In a crossover study, the same person receives both conditions at separate visits. This can make within-person differences informative, but it requires analysis that respects the dependence between measurements and attention to visit order and timing.

The endpoint is a continuous hormone concentration, summarized as a mean with standard deviation. That choice makes it important to distinguish a descriptive summary from an estimate of the insulin-versus-saline contrast. The mean and standard deviation for each condition, the paired difference, and its confidence interval would answer different parts of the statistical question. Those numerical results are not reported in the registry record.

The entry also illustrates why a completed status and an enrollment figure do not establish that the main comparison is interpretable. The record says the primary outcome involves several categories or time points and is not reduced to one comparison. It does not report an analysis, a selected contrast, missing-data handling, or an analysis population. Without those details and the outcome values, readers cannot judge the direction, precision, or robustness of the primary result.

Finally, planning calculations should be kept separate from results. A planning illustration based on an observed effect is not the original sample-size rationale and is not observed power. It cannot resolve the absence of a reported treatment estimate. The statistical value of this registry record is therefore mainly in defining the study question and design, while also making clear what information is unavailable for evaluating the endpoint.

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 most important trial-specific limitation in the registry record is that numerical results for the primary LH endpoint are absent. Although the outcome is identified as a mean concentration in IU/L over 4 hours, the record does not provide condition-specific means, standard deviations, a treatment contrast, confidence interval, or p-value. The primary comparison's direction and precision consequently cannot be assessed.

The registry says the primary outcome has several categories or time points and was not reduced to one comparison. It does not clarify the categories or time points, the analysis chosen for them, or how multiplicity was addressed. The statistical method, analysis population, and handling of missing measurements are also not reported. These omissions prevent assessment of whether the analysis appropriately reflected the crossover structure.

Implementation details are limited. Randomization, double masking, and crossover design are recorded, but the treatment sequence, masking roles, visit interval, and insulin dose are not reported in the registry record. The arm descriptions say patients received insulin at one visit and saline at another; the relation between those descriptions and the Diabetes and Control labels used for adverse events is not clarified.

The recorded enrollment is 14, but the number contributing to the primary endpoint analysis is not reported. The short, 4 hours timeframe also limits what the endpoint can say about outcomes beyond the measured period. The record does not report longer-term results. These limitations concern what can be learned from the registry entry and should not be mistaken for proof that a particular procedure or analysis was not performed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Intranasal Insulin on LH Concentrations in Man — NCT02154477.
• Registry record last updated 2019-08-13; status last verified 2019-07.
• Results first posted 2019-08-13.
• 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

NCT02154477, Effect of Intranasal Insulin on LH Concentrations in Man, is listed as a completed randomized, double-masked crossover trial with Phase 1 and Phase 2 designations. The recorded enrollment is 14, and the sponsor is Texas Tech University Health Sciences Center. The condition listed is hypogonadotropic hypogonadism.

The interventions were intranasal insulin and placebo (intranasal saline). The registry describes patients as receiving each condition at a separate visit. The primary endpoint was mean LH concentration in IU/L, measured over 4 hours. The summary describes obese diabetic men with hypogonadotropic hypogonadism as the study population.

The registry record does not report numerical primary-endpoint results, a statistical comparison, the analysis population, or missing-data handling. It indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Safety counts are reported under Diabetes and Control group labels, but their relationship to the crossover treatment conditions is not clarified.