This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients. (NCT01436045), a randomized phase 2 study. The primary outcome is Cognitive Performance.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01436045 |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | HealthPartners Institute |
| Results posted | Yes |
2. Clinical Question
The study asked whether a single intranasal administration of insulin glulisine was associated with differences in cognitive performance and memory compared with saline in people diagnosed with probable mild to moderate Alzheimer's disease. It also assessed safety and olfactory function. The registry record frames cognitive performance as the primary outcome and olfactory function as a secondary outcome.
Population
People diagnosed with probable mild to moderate Alzheimer's disease. The planned enrollment was 12 participants, and the registry record lists 12 enrolled.
Intervention
A single intranasal dose of insulin glulisine, described in the record as a rapidly acting insulin derivative. Cognitive performance was assessed 20 minutes post-intranasal administration.
Comparator
Saline, used as the placebo. The crossover design specified that participants received both insulin glulisine and saline during separate visits.
Primary question
How did mean total correct responses on the cognitive assessments compare after intranasal insulin glulisine and after saline? The registry lists several cognitive measures but does not reduce them to one reported comparison.
This is a question about the short-term cognitive measurements recorded after a single administration, not about long-term change in cognition or disease progression. The assessment time specified for the primary outcome is 20 minutes after administration. The registry record does not report a single overall cognitive score or a single treatment-effect estimate that combines the listed assessments.
3. Trial Design
The registry identifies this as a phase 2, randomized, quadruple-masked crossover trial. It describes the study as double-blind and placebo-controlled, and records quadruple masking. The design therefore compares insulin glulisine with saline within a crossover framework rather than describing two groups that each receive only one intervention.
According to the arm descriptions, all participants were to receive insulin glulisine and placebo during separate visits. Randomization is recorded, but the registry record does not describe the sequence assignments, how randomization was implemented, or whether the treatment sequences were balanced. It also does not report the interval between visits or any washout procedures. Those details matter when assessing how a crossover comparison was organized and whether effects from one visit could carry into another.
The study was planned as a single-dose investigation. The stated primary outcome was cognitive performance, measured as mean total correct responses, with the assessment scheduled 20 minutes post-intranasal administration. Olfactory function is listed as a secondary outcome. The brief study description also identifies safety as an objective.
The registry lists 12 participants enrolled and describes the study as completed. Its recorded start is 2011-09, and its primary completion is 2013-06. These entries describe the registered study timeline; they do not establish when particular participants attended visits or how long each participant was followed.
The record does not report eligibility criteria beyond the diagnosis and disease-severity description in the study summary, participant characteristics, treatment sequence counts, adherence, or the number of participants contributing data to each outcome. It also does not report a protocol-level explanation of the planned sample size. Without these details, the design can be described from the registered features, but not fully reconstructed.
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
| Stage | Insulin Glulisine, Then Placebo | Placebo, Then Insulin Glulisine |
|---|---|---|
| STARTED | 6 | 6 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | All Study Partipants |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 72 (SD 4.6) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 9 |
| Region of Enrollment: United States | participants | 12 |
| Mini Mental State Examination (MMSE) | units on a scale | 22.17 (SD 2.62) |
| University of Pennsylvania Smell Inventory Test (UPSIT) | units on a scale | 11.8 (SD 2.52) |
6. Primary Endpoint
The registry lists the primary outcome as Cognitive Performance, measured over 20 minutes post-intranasal administration.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | mean total correct responses |
| Endpoint classification | Continuous Endpoint |
The primary outcome is titled Cognitive Performance and is expressed as mean total correct responses. The assessment time is 20 minutes post-intranasal administration. The registry explains that a lower number of correct responses indicates a higher cognitive deficit, so the measure represents performance on cognitive tasks rather than a direct measure of disease progression.
The listed assessments include measures of learning, memory, figure copying and recall, orientation, semantic fluency, digit span, and naming. The registry gives score ranges for many of these measures and notes that semantic fluency has no stated upper limit. These tasks cover different aspects of cognition and use different possible score ranges. The listed results are intended to be means for the individual cognitive assessments, not necessarily a single combined score.
General statistical context: a mean describes the average observed score in the assessed group. It can be useful for describing performance on a measure, but a mean alone does not show how uncertain the estimate is or whether scores differ between treatments. The registry identifies standard error as the dispersion measure. General statistical context: standard error describes the precision of an estimated mean, rather than the spread of individual participants' scores.
The registry record does not report numerical results for the listed cognitive assessments in a single treatment comparison. It therefore does not support a quantitative statement about the size or precision of a difference between insulin glulisine and saline.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies cognitive performance as the primary outcome but lists multiple cognitive assessments rather than one result that summarizes them. It also records that the primary outcome has several categories or time points and is not reduced to one comparison. Consequently, the available record does not establish a single numerical estimate of the difference between insulin glulisine and saline for cognitive performance.
The record does not report means, standard errors, confidence intervals, or p-values for a treatment comparison across the cognitive assessments. It also does not identify which assessment results, if any, were selected as the main basis for an overall conclusion. Without those results, the direction, size, and precision of any treatment contrast cannot be described from the registry record. This is an absence of a reportable summary comparison, not evidence that the treatments produced identical results.
The crossover design means that the planned comparison involved each participant receiving both insulin glulisine and saline at separate visits. General statistical context: a within-participant comparison can account for stable differences between people because each person can contribute observations under both conditions. The treatment contrast still depends on the recorded measurements, the sequence of visits, and the analysis used. The registry record does not report the sequence allocation, visit interval, or statistical model, so those aspects cannot be evaluated.
The primary assessment timing was 20 minutes after administration. This is a short-term measurement following a single dose; it does not answer questions about sustained cognitive effects, repeated administration, or longer-term outcomes. Olfactory function is listed as a secondary outcome, but numerical findings for it are not reported in the registry record.
There were 12 participants enrolled. General statistical context: results from a small enrolled group may be imprecise, and confidence intervals are useful for showing that uncertainty. No confidence intervals are reported in the registry record for the cognitive comparisons. The enrollment number alone cannot establish the precision of an estimate, particularly when the number of participants contributing usable data to each measure is not reported.
The safety figures list 12 participants at risk and zero affected for serious adverse events, as well as 12 at risk and zero affected for other adverse events. The registry does not list serious adverse-event terms. These entries describe the reported counts in this record; they do not establish that no adverse events occurred outside the registry's reporting, nor do they provide a detailed assessment of event type, timing, or severity for non-serious events.
Overall, the record supports a description of the trial question, crossover design, assessment timing, and recorded safety counts. It does not support a numerical conclusion about cognitive benefit, lack of benefit, or the comparative precision of insulin glulisine and saline.
9. Statistical Methods Explained
The registered design and outcome definitions determine what can be interpreted statistically. The study was randomized, quadruple-masked, placebo-controlled, and crossover. Its primary outcome was mean total correct responses across multiple cognitive assessments, with standard error identified as the dispersion measure. The registry record does not report a single numerical treatment comparison for that outcome.
What does a crossover comparison mean?
General statistical context: in a crossover design, participants receive more than one assigned condition at different visits. A comparison can then use the contrast between a participant's measurements under the different conditions. This can be informative because stable characteristics of a participant are shared across their visits. It does not remove the need to consider visit order, period effects, carryover, missing measurements, and the method used to analyze paired observations.
For this study, the arm descriptions say all participants received insulin glulisine and saline during separate visits. The registry record does not report treatment sequences, visit spacing, washout procedures, or a model that accounts for within-participant measurements. Without those details and the outcome values, it is not possible to assess how the crossover structure was handled in the analysis.
What does the mean and standard error describe?
General statistical context: the mean is an average of observed scores. The standard error describes the uncertainty in an estimated mean and is affected by the variability of observations and the amount of information contributing to the estimate. It is distinct from a standard deviation, which describes the spread of individual observations. A standard error can help characterize the precision of a mean, but does not by itself show the treatment contrast or its uncertainty.
The outcome is a mean number of correct responses for each assessment. The tests have different score ranges, and semantic fluency is described as having an unlimited upper range. This makes it important to interpret each measure according to its own definition rather than assume that all test scores can be directly combined. The registry does not identify a combined cognitive score or a prespecified summary across the tests.
What can a confidence interval or p-value contribute?
General statistical context: a confidence interval describes the range of effect estimates compatible with the data and the method used, while a p-value measures how inconsistent the observed data are with a specified null hypothesis under the analysis assumptions. Neither measure indicates clinical importance on its own. The size and direction of an estimated effect, its uncertainty, the outcome definition, and the analysis plan all matter for interpretation.
No confidence intervals or p-values for the cognitive treatment comparisons are reported in the registry record. Since the result is not presented as a single comparison, it would be inappropriate to characterize statistical significance or precision for the primary outcome from these registry entries.
Why do multiple cognitive assessments matter?
The registry describes a range of assessments, including memory, language, attention-related, and visuospatial tasks. When several outcomes are examined, the interpretation can depend on whether a primary measure was chosen in advance, how many comparisons were made, and whether any adjustment or other multiplicity strategy was used. General statistical context: examining many outcomes can increase the chance that at least one result appears notable by chance, depending on the testing strategy. A clear analysis plan helps distinguish a prespecified primary comparison from exploratory findings.
The record notes four outcome measures and two analyses, and that the primary outcome has several categories or time points rather than one reduced comparison. It does not report a multiplicity adjustment or the detailed statistical plan. It is therefore not possible to determine how the analyses addressed multiple measures or comparisons.
What does the planning illustration represent?
The registry-related planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect to detect is expressed as a fraction of the observed effect. These are planning assumptions, not evidence about an observed result. General statistical context: sample-size calculations are conditional on assumptions about the target effect, variability, design, and analysis. A planning illustration based on an observed effect should not be called observed power or interpreted as proof that the trial was adequately powered.
The numerical planning outputs and a protocol-based sample-size justification are not reported in the registry record. The record also does not report the statistical model, analysis populations, missing-data methods, or interim analyses. These omissions limit assessment of how planned comparisons were defined and how the posted results, if any, were derived.
For the safety counts, the record reports the number at risk and the number affected for serious and other adverse events. General statistical context: event counts describe observed reports within the stated group and follow-up context; they do not by themselves estimate comparative risk or rule out events that were not captured or reported. Because this is a crossover study and the safety record gives an all-participant group rather than treatment-specific counts, these figures do not provide a glulisine-versus-saline safety contrast.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is described as cognitive performance, but it comprises multiple cognitive assessments. The registry record notes that the primary outcome has several categories or time points and is not reduced to one comparison. It also lists four outcome measures and two analyses. In addition, olfactory function is named as a secondary outcome. Together, these features make it important to know which comparisons were prespecified and how the analysis accounted for examining multiple outcomes.
The multiplicity strategy, prespecified outcome hierarchy, and detailed analysis plan are not reported in the registry record. It is not possible to determine whether any adjustment was used, whether some analyses were exploratory, or how the two analyses relate to the listed outcome measures. Without a single reported primary contrast, interpretation of any individual test result would require caution.
The record does not describe missing-data handling, participant flow by outcome, or the number of people contributing data to each cognitive measure. It also does not report whether analyses used all randomized participants, only participants with measurements from both visits, or another analysis population. These distinctions can matter in crossover studies because a participant may have measurements for one visit but not another.
The analysis populations and missing-data methods are not reported in the registry record. There is also no description of sensitivity analyses for missing observations or deviations from the planned treatment sequence. Consequently, the completeness and robustness of the reported outcome analyses cannot be assessed from the registry information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Study Partipants | 0 | 12 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Study Partipants | 0 of 12 |
The registry lists an all-study-participants group with 12 participants at risk for serious adverse events and zero affected. For other adverse events, it also lists 12 at risk and zero affected. No serious adverse-event terms are listed. These are the recorded counts in the registry entry.
The deaths field is not populated, so deaths are not reported in the registry record. A missing entry should not be read as a reported count of zero. The record also does not give event descriptions, timing, duration, severity details, or treatment-specific adverse-event counts.
General statistical context: an observed count of zero means that no affected participants are listed in that reporting category for the recorded group. It does not show that the underlying risk is zero, and the count alone does not indicate how precisely risk has been estimated. A small enrolled group and limited event detail restrict what can be inferred about uncommon events. In this crossover study, the all-participant safety figures do not provide a direct comparison of adverse events after insulin glulisine versus saline.
These entries should therefore be read as registry-reported counts, not as a complete account of all possible safety outcomes or a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2 randomized, quadruple-masked, placebo-controlled crossover study evaluated a single intranasal dose of insulin glulisine against saline in people with mild to moderate Alzheimer's disease. The primary assessment concerned mean total correct responses on cognitive tasks, measured 20 minutes after administration. Olfactory function and safety were also part of the study's stated aims.
What the record does not establish is a numerical cognitive treatment effect. The primary outcome comprises several assessments, and the registry does not reduce them to one reported comparison. Means, standard errors, confidence intervals, and p-values for a glulisine-versus-saline comparison are not reported in the registry record. Without those results, the direction and magnitude of a cognitive difference, and its precision, cannot be characterized.
The record also cannot answer whether any short-term measurement reflects a lasting change. The registered assessment time follows a single dose, and the study description does not report long-term outcomes. The findings described by the registry should not be generalized to repeated dosing or to disease progression.
The safety listing records zero affected participants for both serious and other adverse events in a group of 12 at risk. This is a description of the registry's counts, not proof of an absence of risk. The record does not give treatment-specific safety comparisons, and deaths are not reported in the registry record.
General statistical context: a study's design and its reported results answer different questions. Randomization and masking describe how a comparison was intended to be conducted; they do not substitute for outcome estimates and their uncertainty. Here, the record supplies useful design and outcome definitions, but not the numerical treatment results needed to assess how the measured cognitive outcomes differed between conditions.
13. Why This Trial Matters Statistically
This trial is statistically notable for its crossover structure and for the range of cognitive assessments used to represent performance. Each participant was described as receiving both insulin glulisine and saline on separate visits. In principle, this structure permits a within-participant comparison, but interpretation depends on sequence, visit timing, carryover, and the analysis of paired measurements. The registry record does not report those details.
The primary outcome is not a single score in the available description. It includes several cognitive tasks with distinct score ranges and meanings. That makes the choice of primary comparison and the handling of multiple measures important. The registry notes four outcome measures and two analyses, but does not report a detailed multiplicity strategy or a single summary estimate.
The record also illustrates why design descriptions are not enough to evaluate evidence. Randomization and masking can support a controlled comparison, yet a reader still needs effect estimates, uncertainty, analysis details, and participant counts for each outcome. Those cognitive results are not reported in the registry record, so the size and precision of any difference cannot be assessed.
Finally, the safety counts show how event data need context. Zero affected participants are listed for serious and other adverse events among 12 at risk, but the record does not provide treatment-specific counts or detailed event information. Statistically, these counts are descriptive and do not establish a zero underlying risk. The trial therefore offers a useful example of the distinction between a registered design, outcome definitions, and the information needed to interpret comparative results.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record leaves several trial-specific details unavailable. It reports 12 participants enrolled, but does not report participant characteristics beyond the diagnosis of probable mild to moderate Alzheimer's disease. The number of participants with usable data for each cognitive assessment is not reported in the registry record.
The crossover description says participants received insulin glulisine and saline during separate visits, but sequence assignments, visit interval, and washout procedures are not reported in the registry record. Nor does the record describe how the analysis addressed within-participant observations, period effects, or possible carryover. These details are particularly relevant to interpreting a crossover comparison.
The primary outcome comprises multiple cognitive assessments, but no single numerical treatment comparison is reported. The record does not provide the means, standard errors, confidence intervals, or p-values needed to assess the direction, magnitude, or precision of those comparisons. It also does not identify a single combined cognitive score. Results for the secondary olfactory outcome are not reported in the registry record.
The statistical plan, analysis populations, missing-data methods, and multiplicity approach are not reported in the registry record. The record also does not report a protocol-based sample-size justification, interim analyses, or detailed eligibility criteria. These gaps prevent a full assessment of the planned analyses and the completeness of outcome reporting.
For safety, the registry gives all-participant counts rather than treatment-specific counts, lists no serious adverse-event terms, and does not populate the deaths field. It therefore provides limited detail for comparing safety between the two conditions or understanding the nature of events. These limitations concern what can be evaluated from the registry record; they do not establish that the unreported procedures or results were absent from other study materials.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Effectiveness Study of Intranasal Insulin Glulisine on Cognitive and Memory in Mild-Mod AD Patients. — NCT01436045.
- Registry record last updated 2015-10-19; status last verified 2015-09.
- Results first posted 2015-10-19.
- 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.
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18. Record Summary
This completed phase 2 study was randomized, quadruple-masked, placebo-controlled, and crossover. The registry lists 12 participants enrolled and describes a single-dose investigation of intranasal insulin glulisine compared with saline in people with probable mild to moderate Alzheimer's disease. Participants were described as receiving both conditions at separate visits.
The primary outcome was cognitive performance, expressed as mean total correct responses on multiple assessments, with measurement 20 minutes post-intranasal administration. Olfactory function was listed as a secondary outcome. The registry record does not report a single numerical cognitive comparison or the detailed statistical plan, missing-data methods, or multiplicity approach.
The safety entry lists zero affected participants among 12 at risk for serious adverse events and zero among 12 at risk for other adverse events. Deaths are not reported in the registry record. These counts are descriptive and do not provide a treatment-specific safety comparison.