Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis (NCT00028262), a na phase 4 study. The primary outcome is Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells..

2. Clinical Question

In practical statistical terms, the record describes a longitudinal measurement in a treated group rather than a comparison of treatment against a control. That distinction matters: changes observed over time in a single group cannot, on their own, separate treatment-associated change from natural disease progression, time effects, or other influences. The posted information identifies the outcome and its measurement approach, but not the result needed to judge the direction or precision of any change.

3. Trial Design

This is a Phase 4, single-group study with no masking. The registry lists allocation as not applicable and enrollment as 10. The study began in 2001-02, had primary completion in 2013-11, and is recorded as completed. The sponsor is the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The intervention is identified as Cystagon and N-acetylcysteine. The registry summary describes children taking Cystagon by mouth every 6 hours and attending the NIH Clinical Center for a 4- to 5-day period every 6 months for evaluations. It describes medical review and examination, blood tests, clinical photographs, brain MRI, and an electroretinogram, among other assessments. These details describe the study context; the record does not report an outcome result for those evaluations in the primary endpoint information.

The primary endpoint is a continuous measure: the average number of GRODs in peripheral white blood cells. The record gives a 10-year timeframe and says samples before and during treatment were examined by transmission electron microscopy at 30000xmagnification. Two investigators counted deposits independently, and their results were averaged.

One subject did not complete the study and was lost to follow-up. The registry does not report the subject’s outcome status at the point of loss, the timing of loss, or how missing measurements were handled. A planned control group, random assignment, masking, and a detailed statistical analysis plan are not reported in the registry record. Because there is no separate control group, the design can describe within-group measurements over time, but it does not provide a like-for-like randomized treatment contrast.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Out of 10 enrolled subjects, one subject did not complete study and was lost to follow up.

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 Change in Cellular Granular Osmiophilic Deposits (GRODs) in Electron Micrographs of Peripheral White Blood Cells., measured over 10 years.

The primary endpoint is the change in the average number of granular osmiophilic deposits (GRODs) found in peripheral white blood cells. GRODs are the cellular deposits of interest in the study’s biological rationale. The registry describes INCL as an enzyme-deficiency disease in which ceroid accumulates in cells, and notes laboratory observations involving Cystagon and ceroid in cells from patients with INCL.

For the stated endpoint, blood-cell samples obtained before and during treatment were examined using transmission electron microscopy. Two investigators independently identified and counted the GRODs, and the counts were averaged. Averaging the investigators’ counts is the described way of forming the measurement; the registry does not report further detail on how disagreements were handled or whether the investigators were masked to sample timing.

A cellular count can be useful for tracking a biological feature connected to the disease process. It is not, by itself, a direct measure of a child’s symptoms, neurological function, vision, or overall clinical course. The registry’s summary describes other clinical assessments, but the primary endpoint is the GROD count, not a composite of those assessments.

The record labels the outcome as a mean and identifies a 95% confidence interval as its dispersion measure. It does not provide the mean values, the numerical change, the confidence interval limits, or the number and timing of measurements contributing to the result. Therefore, the endpoint definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being measured?

The primary outcome is continuous: it is expressed as an average number of GRODs rather than as a yes-or-no event. The registry identifies the outcome parameter as a mean and the dispersion as a 95% confidence interval. A mean gives a measure of the center of the observed counts. A confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. In general, an interval that is narrower indicates greater statistical precision, while a wider interval indicates less precision. No numerical mean or confidence interval is reported in the registry record, so the endpoint’s observed value and precision cannot be assessed.

How was the cellular measure formed?

The registry says peripheral white blood cell samples from before and during treatment were assessed using transmission electron microscopy at 30000xmagnification. Two investigators counted GRODs independently, and their results were averaged. Independent counting can help reduce reliance on a single observer’s count. As a general measurement principle, however, averaging does not by itself show how consistent the observers’ counts were. The registry does not report agreement statistics, a procedure for resolving divergent counts, or whether the investigators knew the timing of the samples.

What does a single-group design allow?

The study is recorded as single group, with allocation not applicable and no masking. There is no separate control group in the record. A before-and-during-treatment measure can describe the course of the endpoint among observed participants. As a general statistical point, a within-group change is not the same as a randomized treatment effect: without a concurrent comparison, it is difficult to distinguish the influence of treatment from changes that might occur over time for other reasons. The record does not describe a control-based or adjusted comparative analysis.

How should the timeframe be read?

The primary outcome timeframe is listed as 10 years. This indicates the stated period associated with the outcome; it does not reveal how many endpoint measurements each participant contributed, the exact measurement schedule for the endpoint, or whether all participants were followed for the full period. The summary describes visits to the NIH Clinical Center every 6 months, but the outcome record does not provide a participant-level measurement schedule or values at particular visits.

What can be said about statistical testing?

The registry records no analyses for the outcome. It does not report a test statistic, p-value, model, adjustment method, or other inferential result. It also does not report a detailed analysis plan. In general, a statistical test evaluates how compatible observed data are with a specified statistical hypothesis under assumptions; it does not establish causation or clinical importance by itself. Since no test result or estimate is posted, no inference about statistical evidence for change can be made from the registry record.

The record mentions a 95% confidence interval as the dispersion measure, but does not state how that interval was calculated. General methods for confidence intervals depend on the data structure and analysis assumptions. In a repeated-measure setting, observations from the same participant are related, so an analysis that treats all observations as independent could misrepresent uncertainty. The registry does not report the model or variance method used, and it would be inappropriate to infer one.

How do planning illustrations differ from observed evidence?

Sample-size planning calculations are hypothetical illustrations, not results from the enrolled study. In general, such calculations use assumptions about a target effect, variability, significance level, allocation, and statistical model to estimate the amount of information a future study might need. The planning assumptions associated with this record describe a two-arm, equal-allocation normal approximation and a stated fraction of an observed effect. Those assumptions do not match the recorded single-group design. Further, the numerical observed effect needed to interpret such planning values is not reported in the registry record. Any planning illustration should therefore be read as hypothetical rather than as observed power or as evidence about the primary outcome.

These general concepts explain why a defined endpoint and study timeframe are not enough to interpret an effect. Interpretation also requires the actual measurements, a clear account of missing observations, and a statistical method suited to the design. Those details are not reported for the primary result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and records no analyses. It does not describe multiple primary endpoints, a hierarchy of outcomes, or an adjustment for multiple statistical tests. With no reported analysis results, the record does not permit an assessment of whether multiplicity affected interpretation. More generally, when several outcomes or repeated tests are analyzed, the chance of a false-positive finding can increase unless the analysis plan addresses that issue. That is a general statistical consideration, not a claim that such testing occurred in this study.

The registry states that one subject did not complete the study and was lost to follow-up. It does not report the timing of that loss, the number of endpoint measurements available for that subject, or the handling of missing values. There is no reported imputation method, sensitivity analysis, or description of whether missingness was considered in the analysis. In general, incomplete follow-up can affect a longitudinal estimate, particularly if the reason for missing data is related to the outcome. The record does not provide enough information to determine whether that concern applies.

The analysis population is not reported in the registry record. It is therefore unclear whether the endpoint analysis included everyone enrolled, only participants with available measurements, or another defined group. The outcome description’s reference to samples from all patients before and during treatment does not resolve how the one lost-to-follow-up subject was handled in the final analysis.

These omissions limit assessment of completeness and robustness. The registry identifies the endpoint and the loss to follow-up, but does not provide the analysis population or missing-data methods needed to understand how those details affected the reported outcome.

11. 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.

The registry lists a single intervention group, “Drug Cystagon and N-acetylcysteine.” For this group, 9 participants are recorded as at risk for serious adverse events, with 0 affected. It also records 9 at risk for other adverse events, with 0 affected. These figures describe the registry’s reported safety counts for the listed group.

The safety denominator is 9, not the enrollment figure of 10. The record separately states that one subject did not complete the study and was lost to follow-up. It does not explain the relationship between follow-up status and the safety denominator, or provide further detail about the period in which participants were considered at risk. The figures should therefore be read using the reported at-risk group, rather than treated as a complete safety account for every enrolled subject.

The deaths field is not populated with a numerical value. Deaths are therefore not reported in the registry record; this should not be read as a reported zero. No serious adverse event terms are listed. A zero reported count among those at risk describes the posted data, but it does not establish that an event is impossible or characterize risk beyond the recorded group and follow-up.

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

The record establishes that the study examined a cellular outcome in a single group receiving a regimen identified as Cystagon and N-acetylcysteine. It gives a specific measurement approach: GRODs in peripheral white blood cells were counted from electron micrographs, with independent investigator counts averaged. It also specifies a 10-year outcome timeframe.

What the record does not establish is the direction or size of the observed outcome change. The numerical endpoint values and confidence interval are not reported in the registry record. Without them, it is not possible to say whether the measured count changed, how large any change was, or how precisely it was estimated. No analysis result is available to support a statistical conclusion about the primary outcome.

Even if a within-group change were reported, this design would not by itself show that the treatment caused it. There is no separate control group, and the record identifies no random allocation or masking. As a general point, an uncontrolled change over time can reflect influences besides the intervention. A randomized comparison or other suitable design and analysis may help address that question, but no such comparison is described in this registry record.

The biological measure also has a defined scope. A count of cellular deposits is not the same as a direct measure of neurological function, vision, symptoms, or daily experience. The study summary describes clinical evaluations, but the primary outcome information does not provide their results. The record’s laboratory rationale is context for why the cellular measure was of interest; it is not a substitute for clinical outcome evidence.

Thus, the posted information supports understanding the study’s aim, design, and endpoint method, but does not support a conclusion about treatment effect, clinical benefit, or absence of effect. Missing numerical results should be distinguished from a finding of no change.

13. Why This Trial Matters Statistically

This study is statistically notable because it connects a clearly specified cellular measurement with a long-term treatment question in a rare, progressive condition. The primary endpoint is not a broad clinical score: it is the average number of GRODs counted in peripheral white blood cells. The registry gives a description of how investigators formed that measure, including independent counting and averaging, which helps readers understand what the endpoint represents.

The study also illustrates the limits of interpreting a single-group design. Repeated observations can be informative about the course of a measure within a group, but do not create a randomized comparison. This distinction is especially important when the disease is described as progressive, because change over time may occur even without the study intervention. General statistical reasoning therefore calls for caution when connecting an observed trajectory to a treatment effect.

The missing numerical results make the record’s limitations especially clear. A defined endpoint, follow-up timeframe, and measurement procedure do not tell readers the observed effect or its uncertainty. Without an estimate and confidence interval, statistical precision cannot be judged; without a comparator, causal attribution remains limited. The record also notes loss to follow-up but does not explain its implications for outcome completeness.

Finally, the safety counts should be interpreted with their reported at-risk denominator and in the context of the missing follow-up details. Zero reported events in that group is a description of the recorded counts, not proof that risk is absent. Together, these features make the registry useful for identifying the study question and methodological context, while leaving the central efficacy and precision questions unanswered in the posted 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 principal trial-specific limitation is the absence of a separate comparison group. The design is recorded as single group, allocation is not applicable, and masking is none. As a result, the study record does not provide a randomized or concurrent contrast that could separate treatment-associated change from other changes over time.

The primary outcome’s numerical findings are not reported. There is no mean change or confidence interval to evaluate, despite the registry naming the outcome parameter and dispersion measure. The record also lists no analyses, so it does not describe inferential methods, adjustment, or model assumptions for the primary result.

Enrollment was 10, and one subject did not complete the study and was lost to follow-up. The record does not say when this occurred, how much endpoint information was available, how missing measurements were addressed, or which analysis population was used. This makes it difficult to judge the completeness of the 10-year outcome record.

The measurement description notes two independent investigators and averaged counts, but does not report observer agreement, how discrepant counts were handled, or whether counting was masked to sample timing. The endpoint is a cellular measure, and the registry does not provide numerical results for clinical assessments described in the summary. Therefore, the relationship between the primary cellular measure and clinical outcomes cannot be assessed from this record.

Finally, the regimen is identified as a combination in the group name and official title, while the summary’s dosing description focuses on Cystagon. Specific N-acetylcysteine dosing and additional treatment details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis — NCT00028262.
• Registry record last updated 2016-10-27; status last verified 2016-09.
• Results first posted 2015-01-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00028262 is a completed Phase 4, single-group study titled “Cystagon to Treat Infantile Neuronal Ceroid Lipofuscinosis.” The official title describes combination therapy with Cystagon and N-acetylcysteine for INCL patients. Enrollment was 10; the study began in 2001-02 and primary completion was 2013-11. The sponsor is the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The primary outcome is change in the average number of GRODs in peripheral white blood cells, with a 10-year timeframe. The registry describes electron-microscopy assessment and averaging counts from two independent investigators. One subject did not complete the study and was lost to follow-up.

Numerical primary outcome results, confidence interval limits, and analysis details are not reported in the registry record. Safety counts list 0 serious adverse events and 0 other adverse events among 9 at risk; deaths are not reported. The record identifies the study question and measurement method, but does not provide enough result information to quantify the outcome change or its precision.