CDP-Choline and Working Memory After TBI: A Neuroimaging Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CDP-Choline and Working Memory After TBI: A Neuroimaging Study (NCT00727246), a randomized phase 2 study. The primary outcome is Cognitive Composite Score for Group of Subjects With TBI and Healthy Controls Matched by Age, Education, and Treatment Group..

2. Clinical Question

3. Trial Design

The registry describes a completed phase 2 study with randomized allocation, quadruple masking, and a parallel design. Enrollment was 19. The listed interventions were CDP-Choline and placebo. Results for the primary outcome are presented in four groups: participants with TBI who received CDP-Choline, participants with TBI who received placebo, control participants who received CDP-Choline, and control participants who received placebo.

The study began in 2009-03, and primary completion was recorded as 2013-05. The sponsor is Patricia M. Arenth. The registry’s brief summary says the study sought to compare memory, brain imaging, and information collected before and after study medication in people with TBI and people without TBI. The posted primary measure, however, is a cognitive composite score at 6 weeks.

The primary-outcome description says matching was based on age, education, and treatment group, while its fuller description also names age range, gender, and education level as matching criteria. It reports that only 5 subjects with TBI completed the study and that matching required reducing groups to 2 subjects per group for the planned analysis. This is important context for interpreting the posted group estimates: the randomized enrollment and the analysis groups are not the same population size. Reasons for the difference between enrollment, completion, and analyzed group sizes are not reported in the registry record.

The registry does not report further details of the randomization sequence, allocation concealment, or masking procedures. Those details should not be inferred from the design labels alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: A repeated measure ANOVA was completed to evaluate potential differences in cognitive composite scores of subjects with TBI as compared to healthy controls 6 weeks after treatment with CDP Choline (1000 mg CDP-Choline 2 x per day for 6 weeks) as compared to those treated with placebo. Matching criteria and small n for TBI group reduced group sizes.

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 Cognitive Composite Score for Group of Subjects With TBI and Healthy Controls Matched by Age, Education, and Treatment Group., measured over 6 weeks.

The primary endpoint was a cognitive composite score, reported as a T-score, at 6 weeks. The registry describes it as a mean index combining cognitive performance across domains and intended to serve as a measure of overall cognitive functioning. A higher T-score indicates a higher level of cognitive function, according to the endpoint description.

A composite can summarize information from multiple cognitive domains in one measure. In general, this can make an overall pattern easier to evaluate than interpreting many separate test results, but the meaning of the composite depends on how its component measures are selected and combined. The registry record does not report the individual domains, component tests, scoring procedure, or validation details for this composite.

The listed endpoint is relevant to the study’s stated interest in memory and cognitive performance after TBI. It is not itself a direct measure of brain activation or imaging findings. Although the study summary refers to neuroimaging, the posted primary endpoint described in this record is the cognitive composite score. The registry reports group means and 95% confidence intervals for the four TBI/control and treatment combinations, together with an ANOVA result. Interpretation should account for the small matched groups described in the endpoint record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported analysis is an ANOVA, described in the endpoint record as a repeated measure ANOVA. ANOVA is a statistical method for evaluating whether group means differ more than would be expected from variation within groups under the model. The registry reports an overall p-value of .85 for the comparison across the four listed groups. It does not report the test statistic, degrees of freedom, model specification, or a detailed account of the repeated-measures structure.

What does the reported p-value address?

In general, a p-value describes how compatible the observed data are with a specified statistical model in which the tested differences are absent. It is not the probability that a treatment works, nor the probability that the null hypothesis is true. The reported p = .85 is the result of the registry’s ANOVA. Because the record does not provide separate contrast estimates, this p-value should be understood as an overall analysis result rather than as a direct test of CDP-Choline versus placebo specifically among participants with TBI.

An omnibus ANOVA can indicate whether there is evidence of any difference across the groups included in the model, but it does not, by itself, identify which groups differ or quantify a particular pairwise difference. Such interpretation ordinarily requires reported contrasts or follow-up comparisons. Those results are not reported in the registry record. The reported four means can be read descriptively, while avoiding claims that a particular between-group contrast has been formally tested.

How should the confidence intervals be read?

In general, a confidence interval conveys uncertainty around an estimated quantity under the assumptions of the method used. The record reports 95% confidence intervals for each group mean. For the CDP-Choline group with TBI, the mean is 42.75 with a 95% confidence interval from 27.16 to 58.34. For the placebo group with TBI, the mean is 50.5 with an interval from 34.91 to 66.09. For control participants receiving CDP-Choline, the mean is 49.5 with an interval from 33.91 to 65.99; for control participants receiving placebo, the mean is 55.0 with an interval from 39.41 to 70.59.

The intervals are wide relative to the precision needed for fine distinctions between group means. In general, small samples tend to yield less precise estimates, and this record states that each matched group used in the analysis had 2 participants. An interval for an individual group mean is not the same as a confidence interval for a difference between groups. The record does not post intervals for treatment contrasts, so the precision of a specific CDP-Choline-versus-placebo effect cannot be read directly from these group intervals.

Why does the small analysis set matter?

The registry reports that 5 subjects with TBI completed the study and that matching criteria required reducing matched groups to 2 subjects per group for analysis as planned per protocol. This means the reported estimates arise from a very small matched analysis set. In general, results from small groups can be strongly influenced by individual observations, and estimates of variability and treatment effects can be unstable. The endpoint description itself says that the results should be considered with caution because of the small number of participants.

The listed 19-person enrollment is not the denominator for each reported mean. The analysis groups each contain 2 participants. The record does not describe the disposition of every enrolled participant, the reasons for non-completion, or whether any additional participants were excluded from particular analyses. Those omissions limit assessment of how the analyzed groups relate to all randomized participants.

What can be recalculated from the posted summaries?

A recalculated unadjusted comparison requires suitable summary statistics for the two arms being compared. The record identifies that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Therefore, no such recalculated comparison is available. This should not be replaced by calculating a contrast from the four means: the record does not provide the necessary variance information for a valid unadjusted comparison, and the four-group ANOVA is not equivalent to a direct two-arm analysis in the TBI population.

General statistical interpretation also depends on assumptions about the outcome distribution, variance structure, independence, and repeated observations. The registry record does not report diagnostic checks or sufficient model detail to assess these assumptions. The results should consequently be read as the posted descriptive estimates and the sponsor’s reported omnibus ANOVA, with their limited precision and incomplete methodological detail in view.

10. Analyses Reported by the Sponsor

The registry reports a sponsor analysis using ANOVA across the four groups, with p = .85. No recalculated unadjusted two-arm comparison is available for this continuous endpoint because values are missing or not estimable for that comparison. The posted group means and confidence intervals do not supply the summary information needed to generate a valid recalculated treatment contrast.

Accordingly, there is no recalculated estimate to set against the sponsor’s result. The ANOVA p-value is the inferential result reported in the registry, and it should be described as an overall result across the groups rather than as a direct CDP-Choline-versus-placebo test within the TBI group. The record does not provide a treatment-specific contrast, its confidence interval, or the detailed model output needed to extend that interpretation.

The four group means remain useful descriptive information, but they do not resolve the missing contrast. In general, an omnibus test and a pairwise treatment comparison answer different questions. The available record supports reporting the sponsor’s ANOVA as posted, alongside the small analysis groups and broad confidence intervals that limit precision.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 2 analyses, while the number of secondary outcomes with posted results is 0. The primary endpoint described in the record is the cognitive composite score. The brief study summary also mentions memory, brain imaging, and information collected before and after medication, but the details and results for additional outcomes are not reported in the registry record.

When multiple outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. In general, multiplicity procedures are used to address that issue, but the registry record does not report whether any adjustment was planned or applied. It also does not explain how the listed outcome measures and analyses relate to one another, or whether the ANOVA was the only inferential test for the primary endpoint. The p-value should therefore be interpreted as the posted result without assuming a multiplicity strategy.

The record states that 5 participants with TBI completed the study and that the planned matching reduced the groups to 2 participants per group for the primary analysis. The full analysis population, participant flow by randomized group, and reasons for missing observations or non-completion are not reported in the registry record. Methods for handling missing outcomes, including imputation or other adjustments, are also not reported. It is therefore not possible to determine from the posted record whether the analysis retained all randomized participants or how missing data may have affected the estimates.

The registry does not report a complete statistical analysis plan, interim analyses, or the prespecified hierarchy of outcomes and comparisons. Those details should not be inferred from the reported p-value or from the endpoint description. Together, the absence of posted secondary results and limited information on missingness and multiplicity make it difficult to assess the completeness of outcome reporting or the broader testing context.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in the listed groups. The numbers at risk were 3 participants with TBI receiving CDP-Choline, 2 participants with TBI receiving placebo, 7 control participants receiving CDP-Choline, and 3 control participants receiving placebo; the serious adverse event count was 0 in each group. These are small group counts, so the absence of a recorded serious event in these groups is a description of the posted observations, not proof that serious events cannot occur.

The record also lists other adverse events affecting 1 participant with TBI receiving CDP-Choline, 0 participants with TBI receiving placebo, 2 control participants receiving CDP-Choline, and 0 control participants receiving placebo. These are counts and should not be interpreted as comparative rates without additional information. Death counts are not reported in the registry record. The record does not provide serious adverse event terms, and no serious-event terms are listed.

In general, safety counts are most informative when considered with the number of participants observed, follow-up duration, event definitions, and completeness of reporting. The primary outcome timeframe is 6 weeks, but the adverse-event record does not separately describe the observation window or collection methods. The small numbers and limited detail restrict what can be concluded about comparative safety from these entries.

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

The posted results describe cognitive composite scores at 6 weeks in matched groups of participants with TBI and control participants assigned to CDP-Choline or placebo. The means range from 42.75 to 55.0 across the four groups, and each group has 2 participants. The reported 95% confidence intervals are broad and overlap. The overall ANOVA result is p = .85. Taken together, the record does not show a statistically detectable overall difference among the four groups in the reported analysis, while the small analysis groups leave substantial uncertainty about the underlying group means.

This result does not establish that CDP-Choline and placebo are equivalent, nor does it establish that no clinically meaningful difference exists. The analysis is too imprecise to support that kind of conclusion. The ANOVA p-value is not a direct treatment-effect estimate for participants with TBI, and the registry does not report a contrast estimate with a confidence interval for that question.

The result also does not answer every question described in the study summary. In particular, posted primary-outcome information concerns the cognitive composite, not a reported brain-imaging comparison. The record does not provide further results for imaging or other secondary outcomes. The composite’s component measures and scoring details are also not reported, limiting independent assessment of what aspects of cognition it captures.

General statistical interpretation requires separating the observed data from broader claims. These numbers characterize the small matched groups included in the reported analysis. They do not provide a precise estimate for all people with TBI, and they should not be treated as a definitive assessment of treatment effects. The registry itself advises caution because of the small study and small number of TBI completers. The most defensible reading is therefore descriptive: the recorded group means and intervals are uncertain, and the reported omnibus test did not detect an overall difference.

14. Why This Trial Matters Statistically

This study illustrates how the analysis population can become much smaller than the enrollment figure. The registry reports enrollment of 19, but the primary-outcome description says 5 participants with TBI completed the study and that matching required 2 subjects per group for the planned analysis. The resulting means and confidence intervals should be understood in light of that narrow analysis set, rather than as estimates based on everyone enrolled.

It also shows why an overall statistical test should not be mistaken for a specific treatment comparison. The reported ANOVA p = .85 summarizes a comparison among the four groups. It does not provide a direct estimate of CDP-Choline versus placebo among participants with TBI. A reader looking for that treatment contrast needs an estimate and uncertainty interval that the registry does not report, and the posted summaries do not support a recalculated unadjusted comparison.

Finally, the record highlights the value of complete reporting. The four group means, their 95% confidence intervals, and the overall p-value provide some information, but important details are not reported: the test statistic and model specification, analysis populations, missing-data handling, multiplicity strategy, and secondary outcome results. Those omissions limit independent statistical appraisal. The study is therefore useful as an example of how design labels and an overall p-value need to be interpreted alongside group sizes, matching, available estimates, and reporting gaps.

15. 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 very small matched analysis set. The registry states that 5 participants with TBI completed the study and that matching criteria required 2 subjects per group for analysis. Each of the four posted primary-outcome groups has 2 participants. Such small groups yield imprecise means, as reflected by the broad 95% confidence intervals, and make results vulnerable to the influence of individual observations.

The reported ANOVA is not accompanied by a test statistic, degrees of freedom, detailed model specification, or contrast estimates. The registry calls it a repeated measure ANOVA, but the repeated-measures structure and model terms are not described in sufficient detail to evaluate them. A treatment comparison within the TBI group cannot be recovered from the posted summary statistics; the record identifies values as missing or not estimable for a two-arm continuous comparison.

The registry does not report a participant flow account, reasons for non-completion, the complete analysis population, or methods for handling missing data. It also does not report whether multiplicity adjustments were used, how the two listed outcome measures relate to the analyses, or results for secondary outcomes. Details of the cognitive composite’s component domains and scoring procedure are not reported. Although the study summary mentions neuroimaging, corresponding results are not included in the posted primary outcome information.

These limitations mean the reported group values and ANOVA p-value should be read as a limited account of this small matched analysis. They do not allow a precise treatment-effect estimate or a thorough assessment of robustness, missingness, or the broader outcome set.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CDP-Choline and Working Memory After TBI: A Neuroimaging Study — NCT00727246.
• Registry record last updated 2017-07-28; status last verified 2017-06.
• Results first posted 2017-07-28.
• 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.

19. Record Summary

NCT00727246 is a completed phase 2 randomized, quadruple-masked, parallel study of CDP-Choline and placebo in participants with TBI and control participants. Enrollment was 19. The registry lists Patricia M. Arenth as sponsor, with study start in 2009-03 and primary completion in 2013-05.

The primary endpoint was a cognitive composite T-score at 6 weeks. The record reports four group means with 95% confidence intervals, with 2 participants in each group, and an overall ANOVA p-value of .85. It states that 5 participants with TBI completed the study and that matching reduced groups to 2 participants per group for analysis. No usable recalculated two-arm comparison is reported. The record also lists no serious adverse events in the groups, while deaths are not reported in the registry record.