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 Seizure Activity in Alzheimer's Disease (NCT01554683), a randomized na study. The primary outcome is Number of Participants With Evaluable fMRI Scans.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01554683 |
| Phase | NA |
| Condition | Alzheimer's Disease, Seizures |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Beth Israel Deaconess Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with Alzheimer’s disease, in a record that also lists seizures as a condition. The registry describes the research focus as seizure-like activity in Alzheimer’s disease and its relationship to brain blood flow. Enrollment is reported as 12. The record does not further describe eligibility criteria or the characteristics of the enrolled participants.
Intervention
The intervention is listed as low-dose and high-dose Keppra (levetiracetam), administered by intravenous infusion. The arm descriptions reverse the dose labels: the description under “High Dose Levetiracetam” says low-dose administration, while the description under “Low Dose Levetiracetam” says high-dose administration. The record does not resolve this inconsistency.
Comparator
The comparator is placebo administration, described as saline by intravenous infusion. The listed infusion duration is 20 min for the drug and saline descriptions. The randomized, double-masked crossover design indicates that the study was structured around treatment sequences or periods, but the registry record does not report the sequence details.
Primary question
The registered primary outcome is the number of participants with evaluable functional MRI scans. The scans use arterial spin labeling to measure blood-flow changes in specified brain regions, including the hippocampus. The study summary describes the broader research aim as examining whether levetiracetam changes abnormal brain blood flow associated with seizure-like activity. The registry record does not report an analyzed treatment comparison for this endpoint.
3. Trial Design
The registry describes a randomized, double-masked, crossover study of levetiracetam and placebo. The listed intervention includes high-dose levetiracetam, low-dose levetiracetam, and placebo administration. The record gives enrollment as 12 and lists the study status as completed. Its dates are recorded as a start in 2012-02 and primary completion on 2017-07-01.
A crossover design differs from a parallel-group design: participants receive treatments in different periods or sequences, so comparisons may be made within participants. That structure can account for stable differences between people, but it also makes sequence, period, and possible carryover effects relevant to interpretation. The registry record does not report the treatment sequences, period schedule, washout procedures, or analysis methods for the crossover structure. Those details should not be inferred from the design label alone.
The masking field is recorded as double. The registry does not state which roles were masked, how masking was maintained, or whether it was assessed. Allocation is recorded as randomized, but the method used to generate or conceal the allocation is not reported in the registry record.
The arm descriptions contain a material labeling inconsistency: the “High Dose Levetiracetam” description refers to low-dose administration, and the “Low Dose Levetiracetam” description refers to high-dose administration. Both describe an intravenous infusion over 20 min. The placebo description specifies saline by intravenous infusion over 20 min. The record does not explain the discrepancy, so the dose assigned to each named arm cannot be established from these descriptions alone.
The study lists cognitive measures as secondary outcomes, including the Free and Cued Selective Reminding Test, Montreal Cognitive Assessment (MoCA), Trial Making Test Parts A & B, and Phonemic & Category Fluency Test. The registry record does not report results for these measures or explain how they relate to the primary blood-flow endpoint.
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 | High Dose Levetiracetam, Low Dose, Placebo | Low Dose Levetiracetam, High Dose, Placebo | Placebo Administration, High Dose LEV, Low Dose | High Dose LEV, Placebo, Low Dose | Low Dose LEV, Placebo, High Dose LEV | Placebo, Low Dose LEV, High Dose LEV |
|---|---|---|---|---|---|---|
| STARTED | 2 | 1 | 3 | 2 | 1 | 0 |
| COMPLETED | 2 | 1 | 3 | 2 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 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 Participants |
|---|---|---|
| Participants analysed | 9 | |
| Age, Continuous | years | 72 (SD 9.2) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Evaluable fMRI Scans, measured over 3 MRIs acquired at visit 2,3 and 4 between weeks 1 and 6.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The registered primary endpoint is the number of participants with evaluable functional MRI scans. The scan method is arterial spin labeling, which is used to assess perfusion, or blood flow, in specific brain regions, including the hippocampus. The stated timeframe is 3 MRIs acquired at visit 2,3 and 4 between weeks 1 and 6.
As a count of participants with evaluable scans, this endpoint describes whether the imaging data could be assessed, rather than directly stating the size or direction of a blood-flow change. The distinction matters: scan evaluability is necessary for an imaging comparison, but a count of evaluable scans by itself does not establish whether perfusion differed between treatments. To interpret a treatment effect, readers would need the underlying outcome values, a defined comparison, and an analysis that accounts for the crossover design. These results and methods are not reported in the registry record.
The registry’s primary outcome title therefore identifies an evaluability measure, while its description connects the scans to measurement of blood-flow changes. The record does not report the observed count of participants with evaluable scans, the specific brain-region results, or an estimate of treatment-associated change. Nor does it specify how incomplete or unusable scans were handled in an analysis. The endpoint’s stated purpose is scientifically relevant to the study aim, but the registry entry does not provide results that would permit assessment of the blood-flow question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a completed randomized, double-masked crossover study with enrollment of 12. It describes a research question concerning levetiracetam, seizure-like activity, and brain perfusion in Alzheimer’s disease. However, the registered primary outcome is the number of participants with evaluable functional MRI scans, and no analyzed result for that outcome is reported in the registry record. There is therefore no posted primary estimate, uncertainty interval, or treatment comparison to interpret.
The registry record does report adverse-event counts by listed group. For high-dose levetiracetam, low-dose levetiracetam, and placebo administration, it records 9 at risk in each group, with 0 serious events, 0 other events, and 0 deaths for each. These are the recorded counts for the groups; they do not provide a comparative estimate of safety. In particular, a zero count in these entries is not evidence that an event could never occur, and it cannot resolve safety questions beyond the people and reporting captured in this record.
The arm-label inconsistency limits interpretation of the dose groups. The text beneath the high-dose arm names low-dose administration, while the text beneath the low-dose arm names high-dose administration. Until that conflict is clarified, the dose represented by each arm title is uncertain. This issue matters for any dose-specific reading of the posted adverse-event counts or any treatment comparison.
The registry lists secondary cognitive outcomes but does not report their results. It also records 0 analyses, so the posted record does not give inferential analyses for the outcome measures. The primary outcome is flagged as having several categories or time points and not being reduced to one comparison. This means a single summary contrast cannot be reconstructed from the information in the record.
The completion status and primary completion date describe the registry’s status information, not the availability or completeness of analyzed results. A completed study can have results that are not posted in a registry entry. Here, the record supports a description of the intended study question and design, and a narrow account of reported event counts, but not a conclusion about treatment-associated changes in perfusion, cognition, or clinical status.
9. Statistical Methods Explained
Interpreting a clinical trial requires distinguishing the design, the endpoint definition, the analysis, and the uncertainty around the estimated effect. The registry record identifies a randomized, double-masked crossover study, but does not report a primary-outcome analysis. Consequently, statistical concepts can clarify what would ordinarily be needed, but they cannot fill in missing study results or methods.
What does randomization contribute?
Randomization is intended to make treatment assignment less dependent on participant characteristics, supporting a fair comparison. In a crossover study, treatment assignment also concerns the order or sequence in which interventions are received. The registry records random allocation but does not describe its generation, concealment, or the sequence structure. The label alone does not establish how successfully allocation was protected from prediction or influence.
Why does crossover structure matter?
A crossover comparison can use each participant as their own reference, which may reduce the impact of stable differences between participants. But observations from the same person are related rather than independent. Treatment period, order, and carryover can also affect outcomes. A suitable analysis generally needs to reflect these features; treating all period observations as unrelated can misstate uncertainty. The record does not identify the statistical model, any period or sequence terms, or how carryover was considered. These are general considerations, not claims about analyses performed in this study.
What does the primary endpoint represent?
The primary outcome is a count of participants with evaluable fMRI scans, with arterial spin labeling used to measure perfusion in specific brain regions, including the hippocampus. An evaluability count is distinct from a treatment-effect estimate. A treatment-effect analysis would require a defined blood-flow outcome and comparison, along with a method for relating scan measurements to treatment periods. The record gives no observed evaluability count, region-specific estimate, or inferential result. It also does not specify the criteria used to decide whether a scan was evaluable.
How should uncertainty be assessed?
In general, a confidence interval describes a range of estimates compatible with the observed data under the analysis assumptions. Its width conveys precision: a wider interval indicates less precision, while a narrower interval indicates more. A test result or p-value addresses compatibility with a null hypothesis under a specified statistical model, but neither replaces the estimated effect or its uncertainty. No primary estimate, confidence interval, or p-value is reported in the registry record, so the precision and statistical evidence for a treatment contrast cannot be assessed.
Why can over-dispersion matter?
For count outcomes, over-dispersion means that observed variation exceeds what a basic count model would expect. If it is ignored, standard errors can be too small and uncertainty can appear understated. This is a general issue for count data; the primary outcome in this record is a participant count, but the registry does not report a model or a variance assessment. The concern should not be mistaken for evidence that over-dispersion occurred in this study.
What do the planning assumptions mean?
The registry states that its sample-size assumptions describe a planning illustration based on the observed effect, rather than the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed power and not proof that a study had a particular chance of detecting an effect. The record does not report numerical planning results for a primary comparison. The listed primary outcome is also flagged as involving several categories or time points and not reduced to one comparison, which prevents treating it as a single contrast on the basis of this record.
Finally, the crossover design and the adverse-event entries should be read as different types of information. The former describes how treatment comparisons were structured; the latter reports counts by listed group. Neither supplies the missing primary analysis. The arm-description reversal adds another limitation because treatment labels cannot be mapped confidently to the dose descriptions. These considerations define what can be learned from the registry entry and what remains unresolved.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary imaging outcome and several secondary cognitive outcomes. It records 5 outcome measures and 0 analyses. The primary outcome is specifically flagged as involving several categories or time points and not being reduced to one comparison. The record does not explain which comparisons were considered primary within that outcome or how results across regions, visits, or treatment contrasts would be handled.
Multiplicity is the general statistical issue that arises when many outcomes, regions, time points, or comparisons are tested. Without a prespecified approach, repeated testing can increase the chance that at least one result appears notable by chance. The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or a statistical analysis plan. This absence does not establish that no plan existed; it means the approach is not reported in the registry record.
The record also does not describe missing-data procedures or analysis populations. It does not state whether all randomized participants, participants with evaluable scans, or another defined group would be included in the primary analysis. Nor does it report scan completion, reasons for missing or unusable scans, or the handling of incomplete cognitive assessments. Because the primary outcome itself concerns scan evaluability, those details would be particularly important for interpreting the endpoint.
For a crossover study, the analysis population and treatment-period data structure also affect interpretation. The registry does not report whether participants were analyzed according to assigned sequence, actual treatment received, or another rule, and it does not describe how incomplete sequences were treated. None of these choices should be inferred from the completed status or the randomized design.
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 |
|---|---|---|---|
| High Dose Levetiracetam | 0 | 9 | 0.0% |
| Low Dose Levetiracetam | 0 | 9 | 0.0% |
| Placebo Administration | 0 | 9 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| High Dose Levetiracetam | 0 of 9 |
| Low Dose Levetiracetam | 0 of 9 |
| Placebo Administration | 0 of 9 |
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 |
|---|---|
| High Dose Levetiracetam | 0 of 9 |
| Low Dose Levetiracetam | 0 of 9 |
| Placebo Administration | 0 of 9 |
For each listed group—high-dose levetiracetam, low-dose levetiracetam, and placebo administration—the registry reports 9 at risk. Each group has 0 serious adverse events, 0 other adverse events, and 0 deaths recorded. These counts describe what appears in the registry record for the listed groups; they should not be converted into a broader claim about safety.
The record does not define the adverse-event collection period, provide event-specific detail, or explain how the at-risk group counts relate to the crossover periods. It also does not describe whether the same participants contributed to more than one group’s monitoring. The counts therefore should not be added together or interpreted as a count of distinct participants. The arm-description inconsistency further complicates dose-specific interpretation because the named high- and low-dose descriptions are reversed.
Zero reported events does not establish that no adverse events occurred outside the record’s reporting scope, nor does it show that risk is absent. The entries are a descriptive safety snapshot, not a comparative analysis with an estimate of uncertainty. No serious adverse-event terms are listed.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, double-masked crossover study was completed and that its research focus was seizure-like activity, Alzheimer’s disease, and brain blood flow. It identifies levetiracetam and placebo interventions and defines an imaging outcome based on evaluable arterial spin labeling fMRI scans. These details describe the study’s question and structure, but they do not provide the primary results needed to assess a treatment-associated change in perfusion.
The record does not report an observed primary-outcome count, a blood-flow estimate, a treatment comparison, or statistical uncertainty. It also does not report results for the listed cognitive measures. Accordingly, the registry entry cannot establish the direction, size, or precision of a treatment effect on imaging or cognition. The absence of an analysis in the record is not evidence that the study found no effect; it means the relevant result is not reported in the registry record.
The adverse-event entries show 0 serious events, 0 other events, and 0 deaths in each listed group, with 9 at risk in each. These entries describe reported counts only and do not demonstrate that risk is absent or permit a comparative safety conclusion. The crossover structure, missing analysis details, and reversed dose descriptions also limit interpretation.
Thus, the defensible reading is narrow: the record describes a completed study with a stated imaging objective and reports group-level adverse-event counts, while leaving the primary efficacy analysis and its uncertainty unavailable. A registry status of completed should not be confused with a complete public account of the statistical results.
13. Why This Trial Matters Statistically
This study raises a statistical question that depends on linking physiological measurement to a clinically relevant research objective. The registry describes arterial spin labeling fMRI as a way to assess blood-flow changes in brain regions, including the hippocampus, while its primary endpoint is the number of participants with evaluable scans. Keeping scan availability distinct from measured perfusion is essential: successful measurement is not itself evidence of a treatment-related change.
The crossover design also highlights why trial structure matters to analysis. Within-participant comparisons can be informative, but measurements across treatment periods are related and may be affected by order or carryover. Statistical methods should reflect those dependencies. The registry record does not report those methods, so readers cannot determine how the design was incorporated into an analysis.
The entry also illustrates how incomplete reporting constrains interpretation even when study status is marked completed. Without an outcome estimate and its uncertainty, the size and precision of any treatment contrast cannot be judged. The absence of reported analyses also leaves the handling of multiple regions, visits, cognitive outcomes, and missing scans unclear.
Finally, the reversed dose labels in the arm descriptions show why consistency between intervention names and descriptions is not merely editorial. Dose attribution is needed to interpret dose-specific comparisons and safety counts. The record is useful for identifying the research question and design, but its limitations prevent a statistical conclusion about the primary imaging question.
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 primary limitation is the absence of a reported primary-outcome result. The registry defines the endpoint as the number of participants with evaluable fMRI scans, but does not give that count, an analyzed blood-flow comparison, or an estimate with uncertainty. The record also lists 0 analyses, and no results are reported for the secondary cognitive measures.
The primary endpoint description does not state the criteria for scan evaluability or how incomplete imaging data were handled. The record gives a timeframe of 3 MRIs acquired at visit 2,3 and 4 between weeks 1 and 6, but does not report completion by visit or brain region. It is therefore not possible to assess whether missing imaging data could affect the reported endpoint or any intended comparison.
Details needed to evaluate the crossover analysis are not reported in the registry record. These include treatment sequences, period structure, washout procedures, handling of incomplete treatment sequences, and statistical treatment of period, order, or carryover effects. Allocation generation and concealment details, and the roles covered by double masking, are also not reported.
The arm descriptions reverse the dose labels: the high-dose heading is paired with a low-dose description, and the low-dose heading with a high-dose description. The record does not clarify which is correct. Adverse-event counts are descriptive and lack event-specific detail and a stated collection period. Finally, the registry does not report a multiplicity strategy, analysis populations, missing-data methods, or a statistical analysis plan. These gaps limit both efficacy and safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Seizure Activity in Alzheimer's Disease — NCT01554683.
- Registry record last updated 2020-07-23; status last verified 2020-07.
- Results first posted 2020-07-23.
- 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
The registry identifies NCT01554683, “Seizure Activity in Alzheimer’s Disease,” with the official title “Seizure-like Hippocampal Activity in Alzheimer’s Disease Neurodegeneration.” It lists Beth Israel Deaconess Medical Center as sponsor, a randomized, double-masked crossover design, enrollment of 12, and completed status. The recorded start is 2012-02, with primary completion on 2017-07-01.
The interventions are high-dose and low-dose levetiracetam and placebo administration. The primary outcome is the number of participants with evaluable fMRI scans using arterial spin labeling to measure brain perfusion. The record lists cognitive measures as secondary outcomes, but reports 0 analyses and does not report a primary-outcome result. Serious and other adverse-event counts and deaths are recorded as 0 in each listed group, with 9 at risk per group.
The dose descriptions conflict with their arm headings, and the registry record does not resolve that discrepancy. It also does not report the primary analysis, uncertainty estimates, missing-data methods, or details of the crossover analysis.