Glutamine in Preventing Myalgia and/or Arthralgia in Patients Who Are Receiving Paclitaxel For Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Glutamine in Preventing Myalgia and/or Arthralgia in Patients Who Are Receiving Paclitaxel For Cancer (NCT00217724), a randomized na study. The primary outcome is Number of Participants With Response From Glutamine Preventing Paclitaxel Induced Myalgias or Arthralgias After 2 Courses of Chemotherapy.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, crossover pilot study comparing glutamine with placebo for myalgia or arthralgia among patients receiving paclitaxel for cancer. The registry lists the phase as NA and the allocation as randomized. It records an enrollment of 18 and a status of terminated. The start is listed as 1999-07, and primary completion as 2009-01; the reason for termination and any implications of the recorded dates are not reported in the registry record.

The glutamine and placebo arm descriptions specify oral treatment beginning on day 2 of course 1 of paclitaxel administration, taken three times daily for 4 days. The primary endpoint timeframe is 2 courses of chemotherapy (6 weeks). The registry identifies the design as crossover, but does not describe the treatment sequence, any washout period, or how the crossover was implemented. The record says fourteen of the 18 enrolled patients received both cycles and were evaluable for the primary endpoint; it does not explain why other enrolled patients were not evaluable.

In general, a crossover design can allow treatment comparisons within the same participants, but valid interpretation depends on the treatment sequence and on whether effects from an earlier treatment persist into a later period. Those details, and the statistical approach to the crossover, are not reported in the registry record. The double-blind designation indicates masking, but the record does not specify which people were masked or how masking was maintained. It also does not report the randomization method or a sample-size justification. These omissions limit what can be inferred about implementation and analysis beyond the design labels and arm descriptions.

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.

Course 1, (Glutamine/Placebo Arms)

Course 2, (Glutamine/Placebo Crossover)

Analysis population for the primary outcome, as defined in the registry: Fourteen of the 18 patients enrolled received both cycles of therapy and were thus evaluable for the primary endpoint

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 Number of Participants With Response From Glutamine Preventing Paclitaxel Induced Myalgias or Arthralgias After 2 Courses of Chemotherapy, measured over 2 courses of chemotherapy (6 weeks).

The primary endpoint counts participants classified as having a response from glutamine preventing paclitaxel-induced myalgias or arthralgias after 2 courses of chemotherapy. The stated timeframe is 2 courses of chemotherapy (6 weeks). Response is divided into four categories: complete response, partial response, stable disease, and progressive disease. Complete response means complete absence of myalgias or arthralgias. Partial response means symptoms occur but are attenuated in the cycle in which active therapy is received by > 50%. Stable disease is defined as less than 25% change in incidence, duration, or severity. Progressive disease is defined as symptoms worsening by >25% from baseline scores.

This categorical endpoint is intended to represent different degrees of symptom status or change, rather than a single continuous pain score. It can distinguish symptom absence from attenuation, relative stability, and worsening. That may be useful when the clinical question concerns both prevention and reduction of symptoms. However, a category count does not, by itself, show the full pattern of pain scores or the timing and duration of symptoms. The registry record does not report the number of patients in each response category, so the distribution of outcomes cannot be assessed. It also does not explain how symptom diary entries were converted into the primary categories or how incomplete assessments were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, double-blind crossover design and a categorical primary response outcome. It does not provide an analysis plan or report statistical analyses. The explanations below describe general statistical concepts relevant to this design; they should not be read as a description of methods used in this trial unless the registry record states them.

What does randomization tell readers?

In general, randomization is intended to reduce systematic differences in treatment assignment by using chance to allocate participants. It does not guarantee that all characteristics will be balanced, particularly in a small study, and it does not by itself specify how assignments were generated or concealed. The registry says the allocation was randomized, but the sequence-generation method and allocation procedures are not reported. The randomized label therefore describes the design without establishing the quality of every implementation detail.

How does a crossover design affect analysis?

In general, a crossover design exposes participants to treatment conditions in different periods, making it possible to compare outcomes within participants. Measurements from the same person are correlated rather than independent. An analysis that treats such observations as unrelated can misrepresent uncertainty. Crossover studies may also be affected by period effects, changes over time, or carryover if a prior treatment influences a later period. The record identifies the model as crossover and says fourteen of the 18 enrolled patients received both cycles, but does not provide treatment sequences, washout information, or an analysis addressing within-participant correlation, period effects, or carryover. It is therefore not possible to determine how these issues were handled.

What does the categorical endpoint capture?

The primary outcome places participants into complete response, partial response, stable disease, or progressive disease according to the registry definitions. In general, categories can make a multidimensional clinical response easier to describe, while losing detail about the underlying measurements. A patient-level category does not show the exact symptom score, the path of symptoms over time, or the distance between categories. The registry does not report the counts in the categories or explain the rule used to combine symptom incidence, duration, and severity into a classification. Without those counts and rules, the endpoint cannot be independently reconstructed from the record.

How should uncertainty be understood?

In general, an estimate describes the observed treatment contrast, while a confidence interval describes a range of values compatible with the data under the statistical model and its assumptions. A wider interval indicates less precision; a narrow interval indicates greater precision, though it does not establish that an effect is important. A p-value, when reported, measures how incompatible the data are with a specified null model under the chosen analysis. It does not measure the probability that a treatment works or the size of a clinical effect. The registry record reports no treatment estimate, confidence interval, or p-value for the primary endpoint, so neither effect magnitude nor statistical uncertainty can be assessed.

What can the planning assumptions say?

The planning illustrations are described as using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They are based on a stated fraction of the observed effect. These assumptions describe a planning framework, not results from the trial. Any sample-size figures generated from that framework are planning illustrations, not observed power. Observed power is not a substitute for an effect estimate and its uncertainty. The registry does not report a sample-size justification for the original study, and the absence of primary response counts means the observed effect cannot be evaluated from the record.

Why does the outcome scale matter?

In general, the analysis should match the form of the outcome and the design. Counts in response categories are categorical data; an analysis may compare distributions or focus on a prespecified contrast, but the choice depends on the question and plan. A crossover design also requires attention to the dependence between observations from the same participant. The record does not report which contrast or statistical model, if any, was used. It would not be appropriate to infer a test from the outcome title alone or to treat the four response categories as a single binary result without a stated rule.

What do the registry’s analysis entries establish?

The record lists 2 outcome measures and 0 analyses. This means the registry record does not present statistical analyses for readers to assess. It does not show whether investigators performed analyses outside the registry or whether additional results exist elsewhere. Without reported analysis details, readers cannot evaluate model assumptions, adjustment choices, handling of the crossover, or the robustness of findings. Those elements should be treated as not reported in the registry record, rather than inferred from the design description.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures. The primary endpoint is divided into complete response, partial response, stable disease, and progressive disease, while the secondary outcome concerns attenuation of myalgias or arthralgias not receiving glutamine, assessed using pain-scale diaries on days 1 and 3 of courses 1 and 2. Multiple outcomes or category-specific comparisons can create multiplicity: in general, testing several hypotheses can increase the chance of a chance finding if no adjustment or prespecified hierarchy is used. The registry does not report a multiplicity strategy, a hierarchy among outcomes, or an analysis plan. It also reports 0 analyses, so there are no posted tests or adjustments to evaluate.

The primary endpoint population is described as fourteen of the 18 enrolled patients who received both cycles of therapy and were evaluable. The record does not state why other enrolled patients were not evaluable, how missing diary entries were treated, or whether missing outcome data were imputed. It does not report an intention-to-treat analysis, a per-protocol analysis, or sensitivity analyses. Those approaches cannot be presumed from the evaluable-population description. In general, excluding participants with incomplete outcome information can affect interpretation if missingness is related to symptoms or treatment, but the record does not provide enough detail to assess whether that occurred.

The crossover label also makes the analysis population and treatment periods relevant. The record does not say how participants with incomplete periods were handled or whether the primary comparison included only those with information from both cycles. The stated evaluable population indicates who could be assessed for the primary endpoint, but does not explain the rules used to define evaluability. These missing analysis details limit interpretation of both the primary and secondary outcomes.

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 lists the oral glutamine and oral placebo groups with 18 participants at risk in each group. For each group, the reported counts are 0 participants affected by a serious adverse event and 0 participants affected by other adverse events. The deaths field is null for both groups; a null entry is not a reported zero and should not be interpreted as evidence that no deaths occurred.

These safety entries describe the registry’s recorded counts and should be read in the context of its group structure. The study is labeled crossover, so the group entries should not automatically be interpreted as independent sets of participants. The record does not explain the risk period used for these counts, the event definitions, or how adverse events were collected and attributed. It also does not provide event narratives or results for other safety outcomes. A recorded count of zero means no affected participants are listed for that event category in the registry entry; it does not establish that an event was impossible or that safety was fully characterized. The counts do not support a comparative safety conclusion without further methods and context.

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

The registry record documents a randomized, double-blind crossover pilot study of glutamine versus placebo in patients receiving paclitaxel for cancer. It specifies the primary endpoint as a participant response classification after 2 courses of chemotherapy (6 weeks), and defines complete response, partial response, stable disease, and progressive disease. It also identifies fourteen of the 18 enrolled patients as having received both cycles and being evaluable for the primary endpoint. These registry entries describe the question and the available primary analysis population.

The record does not report how those evaluable patients were distributed across the response categories. It also does not provide a treatment contrast, confidence interval, p-value, or secondary-outcome results. As a result, the posted data do not establish the size, direction, or precision of any difference between glutamine and placebo. They do not establish whether symptoms were prevented or attenuated, and they do not establish that there was no effect. Lack of reported results is not a finding of no difference.

The study’s pilot designation and enrollment describe its scale and stated purpose, but do not replace outcome data. A small study may have limited precision, although precision cannot be quantified without estimates and uncertainty measures. The terminated status similarly does not reveal why the trial ended or what the results showed. The registry does not report the reason for termination, the analysis plan, or the missing-data approach.

In general, a clinical result is best interpreted by considering the effect estimate, its uncertainty, the outcome definition, and the population analyzed. Those elements are incomplete or absent in this record. The safety entries list zero serious and other adverse events affected in each group, while deaths are null rather than reported as zero. Those entries should be read as recorded counts, not as proof of complete safety. The registry information supports a description of the trial design and reporting gaps, but not a clinical recommendation or a definitive treatment conclusion.

13. Why This Trial Matters Statistically

This study illustrates why design labels and outcome definitions are not enough to interpret a clinical trial. Randomization, double blinding, and a crossover structure describe important features of the intended comparison, while the response categories specify what the primary endpoint was meant to capture. Yet without category counts, a treatment estimate, and uncertainty measures, the central statistical question remains unanswered in the registry record.

The crossover label is particularly relevant to biostatistical interpretation. In general, a crossover analysis must account for repeated observations from the same participant and consider whether period or carryover effects could influence comparisons. The registry does not report the sequence or analysis details needed to assess those issues. The evaluable population is stated, but the reasons for non-evaluability and the handling of missing information are not. This shows how transparent reporting of participant flow and analysis decisions supports assessment of the results.

The trial also highlights the distinction between a categorical endpoint and the underlying symptom experience. The response categories combine ideas about absence, attenuation, stability, and worsening, but no category counts or scoring details are reported. Readers therefore cannot see the distribution of outcomes or evaluate the practical meaning of the classifications. A clearly described endpoint needs accompanying results to support interpretation.

Finally, registry status and adverse-event entries are not substitutes for efficacy results or a complete statistical report. Termination does not explain the outcome, and zero recorded event counts do not demonstrate that all safety questions have been resolved. The record is useful for identifying the planned comparison and reporting limitations, while also illustrating why estimates, uncertainty, analysis methods, and missing-data information matter.

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 most direct limitation is that the registry record does not report the primary response counts or any statistical analyses. Although the outcome categories are defined, the record does not show how many evaluable patients were classified as complete response, partial response, stable disease, or progressive disease. It therefore offers no primary treatment contrast, measure of uncertainty, or basis for assessing the observed response distribution.

The reported primary analysis population includes fourteen of the 18 enrolled patients who received both cycles. The reason the remaining enrolled patients were not evaluable is not reported in the registry record. Nor are the criteria for evaluability, the handling of missing primary assessments, or the treatment of incomplete diary entries described. Without those details, readers cannot assess potential bias from missing outcome data or determine how closely the analysis population reflects enrollment.

Important crossover details are also absent. The registry does not describe treatment sequences, washout, period effects, carryover, or the statistical method used to account for repeated observations. It identifies randomization and double blinding but does not report how the sequence was generated, which parties were masked, or how masking was maintained. No sample-size justification or multiplicity strategy is reported.

The record states that the trial was terminated but does not give a reason. Safety entries list zero affected participants for serious and other adverse events in each group, while death counts are null; event definitions and observation periods are not reported. These limitations restrict interpretation of both efficacy and safety. They do not show that the trial had a particular result; they show that the registry record lacks information needed to evaluate one.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Glutamine in Preventing Myalgia and/or Arthralgia in Patients Who Are Receiving Paclitaxel For Cancer — NCT00217724.
• Registry record last updated 2017-05-09; status last verified 2017-05.
• Results first posted 2010-09-24.
• 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

This randomized, double-blind crossover pilot study compared oral glutamine with oral placebo for myalgias or arthralgias in patients receiving paclitaxel for cancer. Both arm descriptions specify treatment beginning on day 2 of course 1 and continuing three times daily for 4 days. The primary endpoint classified response after 2 courses of chemotherapy (6 weeks) as complete response, partial response, stable disease, or progressive disease.

The registry records enrollment of 18 and says fourteen participants who received both cycles were evaluable for the primary endpoint. The status is terminated; the reason is not reported in the registry record. Primary response counts, secondary-outcome results, and statistical analyses are not reported. Safety entries list zero serious and other adverse events affected in each group; death counts are null. These details describe what the registry reports, but do not establish a treatment effect or a complete safety profile.