Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy (NCT00195013), a randomized phase 3 study. The primary outcome is Change in Peripheral Neuropathy Score.

2. Clinical Question

The clinical question concerns a short course of glutamine compared with a matching placebo among patients already experiencing mild peripheral neuropathy while receiving paclitaxel. The primary outcome was change in the clinical Total Neuropathy Score, with the endpoint defined as the value at 10 weeks minus the baseline value. Thus, positive change indicates a higher score at follow-up, while negative change indicates a lower score. The score assesses sensory, motor, pin sensibility, vibration sensibility, deep tendon reflexes (DTR), and autonomic symptoms. Each item can range from 0, described as normal, to 4, described as the worst possible result.

The comparison is therefore about the average direction and spread of change in these recorded signs and symptoms in the two randomized arms. The registry record reports mean changes of 0.3 for glutamine and 0.9 for placebo. It also reports the full range of observed changes in each arm. Those summaries describe the recorded participants; they do not, by themselves, establish how certain the difference between arms is or what caused any individual participant’s change.

3. Trial Design

This is a phase 3, randomized, double-masked, parallel-group, placebo-controlled trial. The registry record names Weill Medical College of Cornell University as the sponsor and lists breast cancer and peripheral neuropathy as conditions. The study is marked completed. Its recorded start is 2003-12, and its primary completion is 2014-05.

The recorded enrollment was 30. The primary outcome results include 14 participants in the glutamine arm and 16 in the placebo arm. The registry record describes the trial population as breast cancer patients receiving paclitaxel who had mild symptoms of peripheral neuropathy. It does not report further eligibility criteria, participant characteristics, or the method used to generate the random sequence. Allocation concealment procedures are not reported in the registry record.

Both arms are described as receiving 10 grams three times a day orally for four days and then stopping. One arm received glutamine and the other placebo. The design is listed as double-masked, but which participants, staff, assessors, or other roles were masked is not reported in the registry record. The record also does not describe how the placebo was matched to glutamine.

The primary outcome was assessed over a duration of approximately 10 weeks per subject, with change calculated from baseline to 10 weeks. The record lists one outcome measure and no posted analyses. It does not give a more detailed visit schedule, the timing of the four-day course relative to chemotherapy, or the intended follow-up procedures. A sample-size justification and the statistical plan used to design or conduct the trial are not reported in the registry record. The stated completion status and recorded enrollment describe the study record, but do not supply those missing design details.

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

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 Peripheral Neuropathy Score, measured over Duration of study, approximately 10 weeks per subject.

The primary endpoint is change in the clinical Total Neuropathy Score (TNSc), calculated as the score at 10 weeks minus the baseline score. The registry record says the assessment covers sensory and motor findings, pin and vibration sensibility, DTR, and autonomic symptoms. Each item has a possible score from 0, normal, to 4, the worst possible result. A higher total score represents greater neuropathy severity, so an increase from baseline represents worsening on this scale and a decrease represents improvement on the scale.

A change score focuses on how the recorded score differs between the two assessment times rather than reporting only the score at follow-up. Comparing change by randomized arm is intended to describe how the outcome shifted over the study period in each group. The registry record gives mean changes and full ranges, but does not report standard deviations, standard errors, confidence intervals, or an inferential test for this endpoint.

The TNSc includes several clinical signs and symptoms, which makes it broader than a measure of a single symptom. However, the registry record does not report further details about scoring procedures, assessor training, reliability, or the clinical interpretation of particular change magnitudes. The posted result should therefore be read as a summary of scores on the stated instrument, not as a direct measure of every aspect of participants’ experiences.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts by distinguishing a descriptive summary from an estimate of a treatment contrast. The registry record reports a mean change separately for each randomized arm. Those means describe the recorded outcomes in those arms. A direct comparison would estimate how the average change differs between arms and would ordinarily be accompanied by information about uncertainty. No such inferential comparison is posted for this primary outcome, and the record lists zero analyses.

What does the mean change describe?

The change score is defined as the 10-week score minus the baseline score. In general, a mean change is the arithmetic average of individual changes in a group. It provides a compact account of the group’s overall direction on the outcome, but it does not imply that every participant changed by that amount or in the same direction. In this trial, individual ranges extend below and above zero in both arms, so the reported mean alone cannot describe the distribution of individual experiences. The registry record does not provide the individual observations.

The outcome’s direction is important. The registry record defines an increased score as increased neuropathy severity. Accordingly, a positive change represents a higher score at 10 weeks than at baseline, whereas a negative change represents a lower score. This interpretation applies to the recorded scale; the registry record does not provide a threshold for deciding whether a particular change is clinically important.

What do the ranges tell us?

A full range reports the smallest and largest observed values. The glutamine arm range is -5.0 to 3.0, and the placebo arm range is -6.0 to 7.0. These ranges show that the observed changes were not all identical within either group. A range is not a confidence interval: it does not give a plausible interval for the population mean or for the difference between arms. It also gives no information about how densely participant values cluster within the endpoints. The registry record does not provide a standard deviation or another measure of dispersion.

Why would a confidence interval matter?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. For a treatment comparison, an interval around the between-arm contrast would communicate which effect sizes are consistent with the data and analysis assumptions. It would help distinguish the estimated magnitude from the precision of that estimate. No confidence interval for the primary comparison is reported in the registry record, so the precision of the contrast cannot be assessed from the posted summaries.

A p-value, when reported, addresses compatibility between data and a specified null model; it does not measure the probability that a treatment works or the size of a clinically meaningful effect. No p-value or test result is posted for the primary endpoint. It would therefore be inappropriate to label the result statistically significant or not statistically significant based on the available summaries.

What can be said about planning?

The registry record does not report the trial’s own sample-size justification. It describes a general planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. A planning illustration of this kind is not an observed trial result and does not show the power actually achieved. Because no numerical planning counts or effect fractions are reported in the record, no particular required sample size can be interpreted. A calculation based on an observed effect also depends on that estimate and its uncertainty, so it should not be mistaken for the original design rationale.

General statistical practice also considers whether outcome distributions suit the selected model. If an outcome has more variability than a model assumes, standard errors can be understated and inferential results can become too optimistic; this is one reason over-dispersion matters in analyses that assume a particular variance structure. The registry record does not report a model, a variance assessment, or a dispersion estimate for this continuous change outcome. No claim can be made about whether such checks were used.

Random allocation and masking describe important features of the design, but they do not fill in the absent analysis details. The record does not state the analysis population, missing-data method, handling of baseline values, or whether any adjustment was planned. The posted means and ranges are therefore best treated as descriptive summaries, with the inferential method and its precision not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero posted analyses. It lists no posted secondary outcomes. This limits the evidence available for evaluating multiplicity: there is no reported family of analyses or description of how multiple comparisons, outcomes, or time points were handled. The statistical plan and any prespecified hierarchy of outcomes are not reported in the registry record. The absence of posted secondary outcomes does not establish whether other outcomes were collected or planned.

Missing-data procedures are also not reported in the registry record. The primary outcome summaries give 14 participants in the glutamine arm and 16 in the placebo arm, but the record does not explain whether these are the randomized, treated, or analyzed populations, or whether all participants had both baseline and 10-week scores. It does not state how incomplete measurements, withdrawal, or other unavailable outcomes were handled. Completion status alone does not answer those questions.

The record does not define an intention-to-treat, per-protocol, or other analysis population. It also does not say whether the primary comparison adjusted for baseline score, how deviations from assigned treatment were handled, or whether sensitivity analyses were conducted. These details matter because analysis choices can affect the estimate and its uncertainty. They are not reported in the registry record, so the posted summaries cannot establish which approach was used.

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 5% reporting threshold.

The registry record reports zero serious adverse events among 14 participants at risk in the glutamine arm and zero among 16 participants at risk in the placebo arm. It also reports zero other adverse events among 14 at risk in the glutamine arm and zero among 16 at risk in the placebo arm. These are the counts recorded for the categories and groups described in the registry.

Those zero counts should be read narrowly: they indicate that no affected participants were recorded in these posted categories. They do not show that no symptoms or events of any kind occurred, and they do not establish that the interventions are free of risk. The registry record does not provide event definitions, severity breakdowns for other adverse events, exposure-adjusted rates, or details of how events were collected and monitored. Death counts are not reported in the registry record.

With a limited number of participants at risk, an absence of recorded events cannot exclude uncommon harms. Nor does the posted safety summary establish whether the groups differed in safety. The figures describe the registry’s reported counts and should not be treated as a complete account of every possible event or as a causal comparison.

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

The result does establish what the registry record reports for the primary outcome: mean change in Total Neuropathy Score was 0.3 in the glutamine arm and 0.9 in the placebo arm. The corresponding full ranges were -5.0 to 3.0 and -6.0 to 7.0, respectively. Since an increased score indicates increased neuropathy severity, the positive arm means describe average increases on the score over the assessment period. The ranges show observed changes in both directions within each arm.

The result does not establish that the arm means differ reliably in the population. A confidence interval or inferential test for the contrast is not reported in the registry record. The summaries also do not establish the clinical importance of the observed score changes: no threshold for a meaningful change is reported. The stated scale describes signs and symptoms, but the posted means cannot represent every participant’s outcome or experience.

Randomization is relevant to how the trial was designed, but the registry summary does not provide enough information to assess all features of implementation and analysis. The record does not state the analysis population, how missing values were treated, or whether the reported means reflect a prespecified analysis. It also does not report the original sample-size justification. These gaps limit conclusions about bias, precision, and the strength of evidence.

The safety counts show zero reported serious and zero reported other adverse events in each arm’s listed at-risk group. They do not prove the absence of harms or provide a complete safety profile. Overall, the posted information supports a descriptive account of the recorded primary outcome and adverse-event counts. It does not, on its own, justify a causal or clinical conclusion about glutamine compared with placebo.

13. Why This Trial Matters Statistically

This trial illustrates why reporting the outcome definition is essential to interpreting a numerical result. The endpoint is a change score, and its direction is specified: an increase means increased neuropathy severity. Without that definition, the positive mean changes would be ambiguous. Stating the assessment window and the score’s components also helps readers understand what the reported means represent.

The trial also illustrates the difference between describing each arm and estimating a comparative effect. Arm-specific means and ranges show the outcomes recorded in each group, but they do not provide the uncertainty around the between-arm comparison. A randomized design does not make that uncertainty disappear; it must be estimated and reported using an analysis method. Here, no primary analysis, confidence interval, or test result is posted in the registry record.

Reporting the full range rather than a standard deviation is useful for identifying the observed extremes, but it does not describe the distribution in detail or quantify precision. The ranges span both negative and positive changes in each arm. That spread reinforces the need to distinguish group averages from individual outcomes and to avoid interpreting a mean as a typical experience without more distributional information.

The record further demonstrates the value of transparent reporting about analysis populations, missing measurements, multiplicity, and sample-size planning. Those details are not reported, so readers cannot determine how incomplete outcomes or planned comparisons were handled. Clear reporting would allow a more complete assessment of how the result was obtained and how much confidence to place in the estimate. The available information supports careful description, but not a full statistical evaluation of the comparative effect.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record gives a small set of descriptive primary-outcome summaries: arm sizes, mean changes, and full ranges. It does not provide individual data, standard deviations, standard errors, confidence intervals, or a reported comparison test. The precision of the means and of any between-arm contrast therefore cannot be evaluated from the posted results. The range alone does not resolve this limitation.

The record does not report baseline and follow-up score summaries separately, participant characteristics, or the distribution of scores across the scale’s components. It is not possible to assess whether the arms were similar at baseline from the posted information or to determine which components contributed to the changes. The registry record also does not describe the scoring process or report a threshold for clinical importance.

Important design and analysis details are absent. Allocation concealment, masking roles, the sample-size justification, analysis population, missing-data handling, baseline adjustment, and statistical model are not reported in the registry record. The record lists zero analyses, so there is no sponsor-reported inferential analysis to interpret. It does not say whether all randomized participants contributed to the outcome summaries.

Generalizability is also difficult to assess because additional eligibility criteria and participant characteristics are not reported. The recorded population is limited to breast cancer patients receiving paclitaxel with mild neuropathy, and the described intervention is a four-day oral course. The record does not provide enough information to determine how the results might apply outside that population or regimen. These limitations call for a descriptive rather than definitive reading of the posted data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy — NCT00195013.
• Registry record last updated 2018-06-06; status last verified 2018-05.
• Results first posted 2017-08-18.
• 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.

18. Record Summary

The registry record describes a completed, phase 3, randomized, double-masked, parallel, placebo-controlled trial sponsored by Weill Medical College of Cornell University. Recorded enrollment was 30. The population was breast cancer patients receiving paclitaxel who had mild peripheral neuropathy. Both arms were assigned an oral dose of 10 grams three times a day for four days and then stopped, with glutamine in one arm and placebo in the other.

The primary outcome was change in Total Neuropathy Score from baseline to 10 weeks, over a study duration of approximately 10 weeks per subject. Mean change was 0.3, range -5.0 to 3.0, in the glutamine arm, and 0.9, range -6.0 to 7.0, in the placebo arm. Increased scores indicate increased neuropathy severity. The record lists zero analyses and no posted secondary outcomes. Serious and other adverse-event counts were zero in both arms; death counts are not reported in the registry record.