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 Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer's Disease (NCT00551161), a na phase 4 study. The primary outcome is Changes in the Metabolite Ratios of N-acetylaspartate (NAA) to Creatine (Cr), Myo-inositol (mI) to Cr, Choline (Cho) to Cr, NAA to Cho, and NAA to mI, on Cholinesterase Monotherapy vs Combination of Memantine and Cholinesterase Inhibitor.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00551161 |
| Phase | Phase 4 |
| Condition | Alzheimer Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Northwell Health |
| Results posted | Yes |
2. Clinical Question
Population
Patients with mild to moderate Alzheimer disease who had taken a stable dose of a cholinesterase inhibitor for at least 3 months and had not previously taken memantine. The eligible cholinesterase inhibitors were donepezil, rivastigmine, or galantamine. The registry reports enrollment of 12 participants and describes the outcome population as per protocol.
Intervention
Memantine was added to the participants’ stable cholinesterase-inhibitor treatment during a 24-week open-label period. The arm description says memantine was titrated to a dose of 20 mg per day, in addition to the stable cholinesterase-inhibitor dose.
Comparator
There was no separate control group. Each participant’s earlier 24-week period on stable cholinesterase-inhibitor monotherapy preceded the 24-week period of combination treatment. This is a within-participant comparison across time, not a randomized comparison between groups.
Primary question
Did the changes in five magnetic resonance spectroscopy metabolite ratios during the monotherapy period differ from the changes during the combination-treatment period? The registry describes a Wilcoxon signed-rank test for that contrast. Numerical outcome estimates and the test result are not reported in the registry record.
The study also set out to characterize disease progression using magnetic resonance spectroscopy, cerebrospinal fluid biomarkers, and cognitive outcome measures, and to examine whether changes in cognitive testing correlated with changes in spectroscopy or cerebrospinal fluid biomarkers. Lumbar puncture was optional. The registry record does not report numerical findings for these additional aims, so the relationship between cognition and the biomarkers cannot be assessed from the recorded results.
3. Trial Design
This was a completed, phase 4, open-label, single-group study with enrollment of 12. Allocation was not applicable, masking was none, and the model was single group. These design features mean that the study did not assign participants to separate randomized treatment arms or conceal treatment assignment. The registry lists Northwell Health as sponsor and Alzheimer disease as the condition.
The planned sequence had two periods. During the first 24 weeks, participants continued a stable dose of donepezil, rivastigmine, or galantamine. During the next 24 weeks, memantine was added while the cholinesterase-inhibitor dose remained stable. The arm description specifies open-label memantine titrated to 20 mg per day. The study therefore compared changes across successive periods within participants, rather than comparing concurrently followed intervention and control groups.
Measurements were described at baseline, 24 weeks, and 48 weeks. The primary outcome description refers to measurements at the start of the study, after the monotherapy period, and after the combination-treatment period. This repeated-measure structure permits a comparison between the change in the first period and the change in the second period, but it does not isolate treatment effects from all other changes over time.
The study started in 2007-08 and had a primary completion date of 2011-12. The registry status is completed. The analysis population is described as per protocol, but the number of participants included in the primary analysis is not reported in the registry record. The registry also does not report the protocol’s sample-size justification, detailed statistical plan, or whether interim analyses were planned.
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 | Memantine |
|---|---|
| STARTED | 12 |
| COMPLETED | 11 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Memantine |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Per protocol
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 | Single-arm |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 12 |
| Age, Continuous | years | 76.1 (SD 7.5) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 7 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in the Metabolite Ratios of N-acetylaspartate (NAA) to Creatine (Cr), Myo-inositol (mI) to Cr, Choline (Cho) to Cr, NAA to Cho, and NAA to mI, on Cholinesterase Monotherapy vs Combination of Memantine and Cholinesterase Inhibitor, measured over Baseline, 24 weeks, and 48 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | ratio (normalized to T2-corrected water |
| Endpoint classification | Continuous Endpoint |
The primary endpoint concerns five magnetic resonance spectroscopy metabolite ratios: N-acetylaspartate to creatine, myo-inositol to creatine, choline to creatine, N-acetylaspartate to choline, and N-acetylaspartate to myo-inositol. The registry describes the measurements as ratios normalized to a T2-corrected water signal, assessed using single-voxel proton magnetic resonance spectroscopy. It also describes mean metabolite levels and ratios at baseline, 24 weeks, and 48 weeks.
The planned comparison focuses on whether the change from baseline to 24 weeks differs from the change from 24 to 48 weeks. The first interval represents ongoing stable-dose cholinesterase-inhibitor monotherapy; the second represents memantine added to that treatment. The registry names the Wilcoxon signed-rank test for assessing this contrast. It does not report the numerical mean values, standard deviations, individual ratio estimates, or test results.
Magnetic resonance spectroscopy measures signals associated with metabolites, and ratios can describe their relative levels within the stated measurement framework. General statistical context: a repeated measure can help describe how a measure changes within the same participant over time, while normalization specifies the reference signal used to express the measurement. Those features do not, by themselves, establish that a change was caused by a treatment. The registry’s stated rationale also includes examining relationships between cognitive changes and spectroscopy or cerebrospinal fluid biomarkers, but no numerical results for those relationships are reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary contrast between two successive periods: change during stable cholinesterase-inhibitor monotherapy and change during memantine added to stable cholinesterase-inhibitor treatment. It specifies a Wilcoxon signed-rank test for comparing those changes. However, the posted record does not provide the estimates or test results needed to describe the direction, magnitude, or statistical uncertainty of the primary outcome. The record therefore does not establish whether any of the five metabolite-ratio changes differed between the periods.
For the primary outcome, the registry identifies mean values and standard deviations as the reported measure format, but no numerical values are present in the record. There are no reported confidence intervals or p-values for the primary contrast. Results for the study’s cognitive and cerebrospinal fluid aims are also not reported in the registry record. It is consequently not possible to assess the size or precision of changes, or whether biomarker changes were associated with cognitive changes.
The design calls for measurements at baseline, 24 weeks, and 48 weeks in one group. A within-participant comparison can account for stable differences between participants when changes are analyzed in a paired manner. But the two periods occur in a fixed order, and the registry does not describe a concurrent control group. As a result, a difference between period-specific changes could reflect treatment exposure, the passage of time, measurement variability, or other changes occurring during follow-up. The design alone cannot separate those explanations.
The enrollment was 12, and the outcome population is labeled per protocol. The number contributing to the primary analysis is not reported in the registry record. Without that information, the analysis denominator and any loss of outcome data cannot be established. The record also does not state how missing measurements were handled or whether the analysis included every enrolled participant who had relevant measurements.
Serious adverse event figures are recorded for a single group: 12 participants were at risk and 0 were reported as affected. Other adverse events likewise list 12 at risk and 0 affected. Deaths are not reported. These registry counts describe what was recorded; they do not supply a detailed account of event types, ascertainment, or the duration over which each participant contributed safety data.
Any sample-size values displayed as planning illustrations should be interpreted as hypothetical planning quantities based on an observed effect, not as observed power and not as evidence that the original study was designed to detect a particular effect. The registry record does not report its own sample-size justification. No numerical planning outputs are reported in the registry record available for this analysis. In general, such illustrations depend on their assumptions and should not be treated as additional trial findings.
9. Statistical Methods Explained
The primary analysis is described as comparing two changes in the same participants. For each metabolite ratio, one change is measured from baseline to 24 weeks, and the other from 24 to 48 weeks. The statistical question is whether the distribution of the second-period changes differs from that of the first-period changes, using the contrast written in the registry as (t2 - t1) - (t1 - t0). The registry names the Wilcoxon signed-rank test for this comparison.
What does a paired comparison mean?
General statistical explanation: paired methods work with linked observations, such as measurements taken from the same participant at different times. The pairing matters because measurements from one person are usually not independent of one another. A paired analysis focuses on within-person changes rather than treating each measurement as if it came from a different participant. In this study, the intended contrast compares each participant’s change across one period with that same participant’s change across the other period.
A paired design can reduce the influence of stable differences between participants, because each participant contributes to both periods. It does not remove changes that occur over time or make the periods interchangeable. Here, the monotherapy period always precedes the combination-treatment period in the described sequence. The registry does not describe random assignment of treatment order or a separate group following the same schedule without memantine. Thus, the analysis is a comparison of changes over time in this single group, not a randomized estimate of a treatment effect.
Why use the Wilcoxon signed-rank test?
General statistical explanation: the Wilcoxon signed-rank test is a method for paired data. It uses the signs and ranks of the paired differences, rather than relying on a model that assumes the differences follow a normal distribution. It is commonly used when the analysis is framed around whether paired differences are centered around zero, subject to the method’s assumptions. The registry names this test but does not report further details about its implementation, assumptions checks, or whether any alternative analyses were planned.
The test result would ordinarily be interpreted alongside an estimate of the change and a measure of uncertainty. A p-value alone would not describe the size or practical meaning of a difference. A confidence interval, when reported, describes a range of values compatible with the data and the statistical procedure; it does not guarantee that the true value lies in that range. No test statistic, p-value, confidence interval, or numerical effect estimate for the primary comparison is reported in the registry record.
How should the repeated measurements be understood?
The endpoint description identifies observations at baseline, 24 weeks, and 48 weeks. Those time points map onto the start of the monotherapy period, the end of that period, and the end of the combination-treatment period. The primary contrast is not simply a comparison of the 48-week value with the baseline value. It asks whether the amount of change in the later interval differs from the amount of change in the earlier interval.
General statistical explanation: measurement variation can arise from biological fluctuation, instrument measurement, and other sources. Repeated measurements can help describe the pattern of change, but a small dataset may yield estimates with substantial uncertainty. The registry reports enrollment of 12, but does not report the number with complete measurements at each time point. The precision of the primary comparison therefore cannot be determined from the enrollment count alone.
What is the role of the reported mean and standard deviation?
The registry describes mean metabolite levels and ratios with standard deviations. A mean gives a measure of the center of observed values, while a standard deviation describes the spread of participant values around that mean. General statistical explanation: the standard deviation is not the same as the standard error or a confidence interval. It describes variability among observations; it does not alone quantify uncertainty in an estimated mean or treatment-period contrast. Since the numerical means and standard deviations are not reported in the registry record, their size and pattern cannot be interpreted.
The outcome is continuous, and the registry identifies the mean as its summary parameter. The use of a rank-based paired test alongside mean and standard deviation summaries is not inherently contradictory: descriptive summaries and inferential methods can serve different purposes. But the record does not provide enough numerical detail to reconcile the descriptive values with the test result or assess the distribution of changes.
What can the design establish?
General statistical explanation: a before-and-after sequence can document observed changes within a group. A randomized concurrent control group is often useful for distinguishing changes associated with an intervention from changes that might have occurred over the same period for other reasons. This study is described as single-group and open-label, without a like-for-like control arm. Any period difference therefore needs cautious interpretation and cannot, from this design alone, be attributed uniquely to memantine.
The registry gives no sample-size justification, detailed statistical analysis plan, or information about interim analyses. It also does not report how missing data were handled, whether the five metabolite ratios were treated as separate tests with an adjustment for multiplicity, or how correlations involving cognitive and cerebrospinal fluid measures were analyzed. Those omissions limit assessment of the analysis choices and the chance of false-positive findings across multiple outcomes. They should not be filled in by assuming standard practice.
Planning illustrations are conceptually distinct from observed trial findings. General statistical explanation: a planning calculation may use an assumed effect, allocation, significance level, and statistical model to estimate the sample size needed under those assumptions. The calculation is not evidence that a study had that probability of detecting an effect after the fact. The registry’s illustration description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, but this trial itself is not a two-arm randomized comparison. The registry does not report the trial’s own sample-size rationale. Any planning illustration should therefore be read as a hypothetical scenario, not as a feature of the enrolled study or a substitute for reported results.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome includes five metabolite ratios. Testing several ratios raises a general multiplicity issue: when multiple hypotheses are tested, the chance of at least one apparently unusual result can increase if each test is judged separately without an adjustment. The registry does not report whether the five ratios were handled as one family of tests, whether an adjustment was used, or whether one ratio was designated as more central than the others. The numerical test results are not reported in the registry record, so the effect of any multiplicity approach cannot be assessed.
The study’s stated aims also include cognitive measures, cerebrospinal fluid biomarkers, and correlations between those measures and magnetic resonance spectroscopy changes. The registry does not describe a hierarchy among these aims or report whether these additional analyses were prespecified as confirmatory or exploratory. The study is identified as exploratory in its official title, but detailed analysis procedures for the secondary aims are not reported in the registry record.
The registry labels the primary outcome population as per protocol. It does not report the number analyzed, the number with measurements at each time point, reasons for missing measurements, or methods used to address missing data. Optional lumbar puncture is described, but the record does not report how many participants underwent it or how missing cerebrospinal fluid measurements were handled. Without such details, the impact of incomplete observations cannot be evaluated.
General statistical explanation: complete-case analyses can be affected when the participants with observed data differ systematically from those without observed data. Other missing-data methods rely on their own assumptions. No particular approach can be attributed to this study from the registry record. The analysis population label alone does not establish how deviations, incomplete follow-up, or missing outcomes were treated.
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 |
|---|---|---|---|
| Single-arm | 0 | 12 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Single-arm | 0 of 12 |
The serious adverse event record lists a single group, with 12 participants at risk and 0 affected. The record also lists 12 participants at risk and 0 affected for other adverse events. These are registry counts, not a comparison between treatment and control groups, because the study had a single-group design.
Deaths are recorded as null, so the death count is not reported in the registry record. No serious adverse event terms are listed among the top serious terms. A count of 0 affected means that the registry reports no participants affected in that category; it should not be expanded into a claim about specific event types, severity patterns, or surveillance procedures not described in the record.
General statistical explanation: safety counts are most informative when read with clear definitions, observation periods, and denominators. The registry identifies the number at risk but does not provide detailed participant-time, event narratives, or information about how events were collected and classified. The counts should therefore be read as the recorded safety summary, not as a complete description of every aspect of safety monitoring or as a comparison of relative safety between treatments.
12. What the Result Does, and Does Not, Mean
The record describes a small, completed, open-label study examining magnetic resonance spectroscopy ratios across a stable cholinesterase-inhibitor period and a later period when memantine was added. Its primary statistical question is whether the changes in the two periods differed within participants. The registry specifies the outcome measures and the Wilcoxon signed-rank test, but does not report numerical primary results. It is therefore not possible to state the direction, size, or precision of the observed differences.
The study’s stated aims extend to cognition and cerebrospinal fluid biomarkers, including whether changes in cognitive function correlate with changes in spectroscopy or cerebrospinal fluid measures. Numerical findings for those aims are not reported in the registry record. The record consequently does not allow an assessment of whether those measures changed, how they related to one another, or how uncertain any associations were.
The single-group sequence is useful for describing measurements across time in the enrolled participants, but the periods are not a randomized treatment comparison. Changes across the later interval may coincide with memantine exposure, yet the design does not by itself distinguish treatment-associated change from time-related change, measurement variation, or other influences. The open-label design also means treatment was not masked, although the registry does not state how this affected measurement or analysis.
These limitations do not mean that the study’s measurements are uninformative. They define what can be concluded from the registry record: the study was designed to explore longitudinal biomarker and cognitive patterns, and it recorded a specific within-participant contrast. Without posted outcome estimates and analysis details, however, neither the magnitude of any pattern nor its statistical precision can be judged. The safety counts likewise report no affected participants in the recorded categories among 12 at risk, while deaths are not reported.
13. Why This Trial Matters Statistically
This study illustrates a common statistical challenge in exploratory clinical research: several biological measurements are collected repeatedly, while the treatment sequence and the available comparison structure constrain what can be inferred. Measuring the same participants at baseline, 24 weeks, and 48 weeks creates a paired longitudinal framework. The registry’s contrast compares changes across two successive periods rather than simply comparing an endpoint value with baseline.
That approach makes the statistical question explicit, but it does not turn a single-group before-and-after study into a randomized comparison. Because the combination-treatment period follows the monotherapy period, treatment exposure and time are linked in the design. A difference between period changes can be described, but the design alone cannot determine which factors produced it.
The study also highlights why complete reporting matters. The registry names five metabolite ratios, descriptive summaries, and a paired test, yet numerical estimates, uncertainty intervals, and test results are not reported in the registry record. Without those results, readers cannot assess the direction, scale, or precision of the primary findings. Without details on multiplicity and missing observations, readers also cannot fully evaluate the analysis across the several measurements and study aims.
Finally, the work connects imaging biomarkers, cerebrospinal fluid biomarkers, and cognitive outcomes. Such relationships are scientifically distinct from a treatment-period contrast and require their own clearly reported analyses. The registry’s description makes those aims visible, while the absence of numerical findings means their results cannot be interpreted from this record. The study is therefore statistically informative as an example of an exploratory repeated-measures design, but its posted record does not support a quantitative conclusion about the measured changes.
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 for interpreting results is that the registry record does not report numerical estimates for the primary outcome. Although it specifies five metabolite ratios, three assessment times, summary statistics, and a Wilcoxon signed-rank test, it gives no values for the ratios, no test statistics or p-values, and no confidence intervals. The size and precision of any period difference are therefore unknown from the record.
The study’s single-group, open-label design provides no concurrent control group and no masking. The monotherapy period precedes the combination-treatment period, so the comparison is vulnerable to effects of time and other changes over follow-up that are not separated from the treatment sequence. The study can describe within-participant changes, but the design does not independently establish their cause.
Enrollment was 12, while the number included in the per-protocol analysis is not reported in the registry record. There is no reported accounting of completion at each measurement time, missing measurements, withdrawals, or the handling of incomplete observations. Optional lumbar puncture introduces additional uncertainty about the availability of cerebrospinal fluid measurements, but the record does not state how many participants provided them.
Five primary metabolite ratios are named, and additional cognitive and biomarker aims are described. The record does not report whether analyses were adjusted for multiplicity, how secondary analyses were specified, or whether interim analyses were planned. The protocol’s sample-size justification and detailed statistical analysis plan are also not reported. These gaps limit evaluation of precision, analysis choices, and the robustness of any results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Magnetic Resonance Spectroscopy Study of Memantine in Alzheimer's Disease — NCT00551161.
- Registry record last updated 2014-01-28; status last verified 2013-12.
- Results first posted 2013-12-18.
- 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
NCT00551161 is a completed phase 4, open-label, single-group study sponsored by Northwell Health, with enrollment of 12 and Alzheimer disease listed as the condition. It studied patients with mild to moderate disease who were already taking a stable cholinesterase inhibitor and had not previously taken memantine.
Participants continued stable cholinesterase-inhibitor treatment for 24 weeks, followed by 24 weeks of open-label memantine added to that treatment. The primary outcome concerned five magnetic resonance spectroscopy metabolite ratios measured at baseline, 24 weeks, and 48 weeks. The registry describes a Wilcoxon signed-rank test comparing changes across the two periods.
The stated aims also included cognitive measures, optional cerebrospinal fluid biomarkers, and correlations among changes in these measures. Numerical results for the primary and additional aims are not reported in the registry record. The safety record reports 0 serious adverse events and 0 other adverse events among 12 at risk; deaths are not reported.