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 A Study of Oxidative Pathways in MS Fatigue (NCT02804594), a randomized phase 2 study. The primary outcome is Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02804594 |
| Phase | Phase 2 |
| Condition | Progressive Multiple Sclerosis, Fatigue |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 15 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
Participants with progressive multiple sclerosis and fatigue, defined by McDonald criteria, who entered the treatment period. The registry record lists enrollment of 15.
Intervention
N-acetyl cysteine, at 1250 mg three times daily for 4 weeks.
Comparator
Placebo, taken three times daily for 4 weeks.
Primary question
How many adverse events reported since baseline and related to N-acetyl cysteine occurred in the treatment group, compared with adverse events reported by participants in the placebo group?
The trial also lists changes in fatigue questionnaire scores and blood-marker levels from baseline as secondary outcomes. The focus of the posted primary outcome is not whether fatigue improved: it is the number of adverse events attributed to N-acetyl cysteine over the 4-week timeframe.
The registry reports 12 adverse events in the N-acetyl cysteine group and 6 in the placebo group. The group sizes were 10 and 5, respectively. These are event counts, not counts of participants who experienced an event, and they do not by themselves establish how the groups compare. In particular, the registry record does not report a statistical analysis or an estimated between-group effect for this primary outcome.
The study is described as a Phase 2, randomized, double-blind, parallel-group, single-center trial. Its question is therefore framed as a comparison between assigned groups during treatment, rather than a comparison of each participant with an untreated baseline period. The record does not report the results of the listed fatigue and blood-marker secondary outcomes.
3. Trial Design
This was a Phase 2 randomized, placebo-controlled, double-blind, parallel-group, single-center study. It compared N-acetyl cysteine with placebo among people with progressive multiple sclerosis and fatigue. The registry record lists enrollment of 15 and reports 10 participants in the N-acetyl cysteine group and 5 in the placebo group. The record marks the study as completed.
The intervention period was 4 weeks. Participants assigned to N-acetyl cysteine were to take 1250 mg three times daily; participants assigned to placebo were to take placebo three times daily. The summary describes three in-person visits: screening, baseline, and week 4. It also describes phone visits at week 2 and week 6, with week 6 occurring 2 weeks after the last study-drug dose.
The summary states that visits were scheduled in the morning to promote consistency of assessments and to assess main outcomes within 2 hours of the morning dose. Fatigue questionnaires and research samples were to be obtained before neurological examination or magnetic resonance imaging. Research blood draws were to follow completion of fatigue questionnaires. Brain spectroscopy was to occur less than 2 hours after the morning dose.
Randomization and double masking are stated in the registry, but details of the randomization sequence, allocation concealment, and who was masked are not reported in the registry record. The record does not report whether adherence was assessed or how it was summarized. Its posted primary outcome is a count of adverse events related to N-acetyl cysteine during 4 weeks; the listed secondary outcomes concern changes in fatigue scores and blood markers from baseline.
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.
Before assignment: Study participants who met the eligibility criteria to enroll in the study are randomized into study medication group or placebo group. Study participants who did not meet the criteria to enter the study treatment period of the study were observed as controls.
Overall Study
| Stage | N-acetyl Cysteine | Placebo |
|---|---|---|
| STARTED | 10 | 5 |
| COMPLETED | 10 | 5 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Study participants enrolled in the treatment period are included in the analysis.
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 | N-acetyl Cysteine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 5 | 15 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 2 | 11 |
| Age, Categorical: >=65 years | Participants | 1 | 3 | 4 |
| Age, Continuous | years | 51.3 (SD 9.2) | 65.7 (SD 6.8) | 56.1 (SD 10.8) |
| Sex: Female, Male: Female | Participants | 8 | 4 | 12 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 5 | 14 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 10 | 5 | 15 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 10 | 5 | 15 |
| Modified Fatigue Impact Scale (MFIS) score at baseline | Scores on a scale | 48.5 (46 to 56) | 50 (45 to 52) | 50 (45 to 56) |
6. Primary Endpoint
The registry lists the primary outcome as Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine., measured over 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of adverse events reported since the baseline visit that were related to N-acetyl cysteine. Its timeframe is 4 weeks, and the registry description says the count for the N-acetyl cysteine group will be compared with the number of adverse events reported by participants in the placebo group. The analysis population is described as study participants enrolled in the treatment period.
Event counts can capture more than whether any participant experienced an event: a participant may contribute more than one event to a count. That makes it important to distinguish an event total from the number of participants affected. The posted primary values are 12 events for N-acetyl cysteine and 6 for placebo. They do not identify how many participants contributed those events or how events were distributed among participants.
As a general statistical rationale, counting adverse events can describe the burden of events during treatment and can be useful when events may recur. Interpretation requires care, because a larger event total could reflect more participants having events, repeated events in a smaller number of participants, or both. The registry record does not report event-level detail, an analysis accounting for recurring events, or a comparative estimate with uncertainty. Therefore, the counts describe the recorded outcomes but do not on their own quantify a treatment-group difference or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome is a count, not a proportion of participants with at least one event. The registry reports 12 adverse events related to N-acetyl cysteine in the N-acetyl cysteine group and 6 in the placebo group. The corresponding group sizes are 10 and 5. The event totals should not be read as if they were participant totals: the record does not say how many people experienced at least one event, how many events each person experienced, or whether events were counted using a particular coding convention.
The registry record explicitly indicates that values are missing or not estimable for a two-arm comparison for this count endpoint. It reports no analyses, and no comparative estimate, confidence interval, or p-value is posted for the primary outcome. Consequently, the recorded counts do not establish the size or precision of a between-group effect. They also do not support a claim that one group had more risk or that the groups were equivalent.
The group sizes differ, so the raw event totals are not a like-for-like comparison of rates. No event rate should be inferred from these values, and no adjustment or model-based estimate is reported. Calculating a rate or a statistical comparison from the summary counts would require assumptions about event exposure, within-participant recurrence, and the way events were collected. Those details are not reported in the registry record.
The adverse-event summary separately reports 0 serious adverse events and 0 deaths in each group. It also reports other adverse events affecting 6 participants in the N-acetyl cysteine group and 4 in the placebo group. Those figures describe affected participants for the other-adverse-event summary, whereas the primary endpoint counts events related to N-acetyl cysteine. They answer different descriptive questions and should not be combined or treated as interchangeable.
Two secondary outcomes are named: change in fatigue questionnaire scores from baseline and change in blood-marker levels from baseline. The registry lists 4 outcome measures but reports 0 analyses. Results for the named secondary outcomes are not reported in the registry record. Thus, the available posted results support description of the reported event counts and safety summaries, but not an inferential conclusion about the primary comparison or the secondary outcomes.
The record does not report a statistical analysis plan, a sample-size justification, an interim analysis, or methods for handling missing outcome data. The absence of a posted estimate is especially relevant for a small trial: without a model and a measure of uncertainty, the observed counts cannot establish how compatible the results are with a range of possible group differences. The record's descriptive numbers should be read as the reported observations, not as a definitive estimate of comparative safety.
9. Statistical Methods Explained
The registry identifies the primary outcome as a count of adverse events related to N-acetyl cysteine and reports a value for each randomized group. It does not post an analysis of that count. The registry also notes that values are missing or not estimable for a two-arm comparison. This distinction matters: having a number in each arm is not the same as having an estimated treatment contrast, and the posted record does not give a confidence interval or significance test for the primary outcome.
What does a count measure?
A count records how many events occurred over a defined period. In this trial, the period is 4 weeks, and the primary description concerns events reported since baseline. A count may include multiple events from the same participant. In general, count data are often analyzed with methods that reflect both the amount of observation time and the possibility that events recur. If observations vary more than a simple model expects, over-dispersion is one concern: it means the data are more variable than that model allows, and uncertainty estimates from an overly simple model can be misleading.
Those are general statistical considerations, not a description of the analysis used in this trial. The registry record does not identify a count model, an offset for exposure time, an approach to recurrent events, or any other method for comparing the arms. It also does not give the participant-level event distribution or the time each participant was observed. As a result, it is not possible to determine from the record whether a particular count-data method would be suitable or to reproduce a model-based comparison.
Why are the arm totals not enough for an effect estimate?
The reported event totals are 12 and 6, while the group sizes are 10 and 5. An event total alone does not show whether events were spread across participants or concentrated among a few. That distribution affects the variability of a count and may affect the uncertainty of a comparison. The record also does not report whether all participants contributed the same observation time, or whether there were missing reports or differences in follow-up. These unknowns prevent a reliable reconstruction of an event rate or a comparative estimate from the posted summary.
A confidence interval, as a general concept, gives a range of values compatible with the data and a specified statistical procedure. It communicates precision, not certainty that the true effect lies in a particular range. No confidence interval is posted for this primary outcome. A p-value, also not posted, would address compatibility with a specified null hypothesis under a specified analysis; it would not show the probability that a treatment effect is true. Without the analysis and its assumptions, neither quantity can be interpreted for this endpoint.
What can randomization and masking contribute?
Random assignment is intended to support a fair comparison by making group assignment independent of measured and unmeasured participant characteristics on average across repeated assignments. In a small study, randomization does not ensure that characteristics will be balanced in the realized groups. The registry states that allocation was randomized and masking was double, but does not report sequence generation, allocation concealment, or which roles were masked. Randomization and masking strengthen the design, but they do not replace a reported analysis or resolve uncertainty in the observed count.
The parallel-group design compares outcomes between people assigned to the two groups during the same trial period. The summary describes morning assessments and a 4-week treatment period. It does not report a model that adjusts for baseline characteristics, repeated visits, or exposure time. No adjustment should be presumed.
What do the planning assumptions mean?
The record describes planning illustrations based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence about the trial's actual design rationale. No numerical planning estimates are reported for this count endpoint: the record says values are missing or not estimable for a two-arm comparison. The sample-size justification and the statistical plan are not reported in the registry record.
More generally, a planning sample size depends on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. If those assumptions do not match the eventual outcome distribution, the planning result may not describe the precision achieved. Because no numerical estimates or endpoint-specific comparison are posted here, there is no basis for interpreting sample-size planning as a statement about the strength of the observed evidence.
10. Multiplicity, Missing Data and Analysis Populations
The registry names two secondary outcomes: change in fatigue questionnaire scores from baseline and change in blood-marker levels from baseline. It lists 4 outcome measures in total, but only those two secondary outcomes are named in the record. Results and analyses for those outcomes are not reported in the registry record; the record lists 0 analyses.
When several outcomes are tested, the chance of finding at least one apparently noteworthy result can increase if each is assessed separately without accounting for multiplicity. This is a general statistical issue, not evidence that a particular adjustment was or was not applied in this trial. A multiplicity plan, hierarchy among outcomes, or correction procedure is not reported in the registry record. No conclusions about secondary-outcome testing or adjustment can therefore be drawn.
Missing-data methods are also not reported in the registry record. The record does not state whether all participants completed every assessment, how incomplete questionnaires or blood-marker measurements were handled, or how missing adverse-event information was addressed. It describes the primary analysis population as participants enrolled in the treatment period, but does not give further inclusion rules or an analysis-population label such as intention-to-treat.
The registry's statement that a two-arm comparison is not estimable for the count endpoint should not be mistaken for a missing-data method or an inferential result. It indicates that the record does not provide an estimable comparison for that outcome. The reason for this status and any analysis attempts are not reported in the registry record. Without analysis details and outcome completeness information, the potential impact of missing observations and multiplicity cannot be assessed.
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 |
|---|---|---|---|
| N-acetyl Cysteine | 0 | 10 | 0.0% |
| Placebo | 0 | 5 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| N-acetyl Cysteine | 0 of 10 |
| Placebo | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| N-acetyl Cysteine | 6 of 10 |
| Placebo | 4 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | N-acetyl Cysteine | Placebo |
|---|---|---|---|
| Gait disturbance | General disorders | 1 of 10 | 1 of 5 |
| Insomnia | Psychiatric disorders | 1 of 10 | 0 of 5 |
| abdominal pain | Gastrointestinal disorders | 1 of 10 | 0 of 5 |
| Constipation | Gastrointestinal disorders | 1 of 10 | 0 of 5 |
| BACK PAIN | Musculoskeletal and connective tissue disorders | 0 of 10 | 1 of 5 |
| Salivary gland infection | Infections and infestations | 1 of 10 | 0 of 5 |
| Respiratory-Other, Common cold | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 5 |
| Fatigue | General disorders | 0 of 10 | 1 of 5 |
| Depression | Psychiatric disorders | 0 of 10 | 1 of 5 |
| Urinary tract infection | Infections and infestations | 0 of 10 | 1 of 5 |
The registry's serious-adverse-event summary reports 0 serious adverse events among 10 participants at risk in the N-acetyl cysteine group and 0 among 5 participants at risk in the placebo group. It reports 0 deaths in each group. No serious adverse-event terms are listed. These are the serious-event figures recorded for the trial, not proof that serious harm is impossible or that the groups have identical safety profiles.
The registry also reports other adverse events affecting 6 participants in the N-acetyl cysteine group and 4 in the placebo group, with 10 and 5 participants at risk, respectively. This is a count of participants affected in the other-adverse-event summary. The primary endpoint, by contrast, is a count of adverse events related to N-acetyl cysteine, reported as 12 and 6. An affected-participant count and an event count are different measures and should not be substituted for one another.
These summaries are descriptive. The registry record does not report uncertainty intervals, a formal comparison, event severity or type for the other events, or participant-level recurrence information. The results therefore characterize what was posted, but do not provide a precise estimate of comparative safety.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry records 12 primary-endpoint adverse events related to N-acetyl cysteine in the N-acetyl cysteine group and 6 in the placebo group during the stated 4-week timeframe. They also establish that the group sizes were 10 and 5, and that the serious-adverse-event and death counts were 0 in both groups. These statements describe the posted data; they do not establish a causal difference between assigned treatments.
The primary values are event totals, not numbers of participants with at least one event. The separate other-adverse-event summary reports affected-participant counts, but those figures do not identify how many people contributed to the primary event totals. Without participant-level distribution, event timing, exposure information, and an analysis model, the totals cannot be turned into a reliable comparative rate or effect estimate.
The registry does not report a two-arm estimate, confidence interval, p-value, or analysis method for the primary endpoint. Therefore, the numerical difference between the posted event totals is not enough to establish the direction, magnitude, or precision of a treatment effect. Similarly, 0 serious adverse events in each group does not demonstrate that the treatments have the same serious-event risk; the record contains no inferential comparison for that outcome.
The trial was randomized and double-blind, which are design features relevant to reducing bias in a comparison. They do not guarantee balance in a small study or supply information absent from the outcome analysis. The registry record also names fatigue and blood-marker changes as secondary outcomes, but their results are not reported. No conclusion about those outcomes can be drawn from their inclusion in the record alone.
Overall, the registry supports a limited descriptive reading of the reported adverse-event counts and serious-event summaries. It does not support a claim that N-acetyl cysteine is beneficial, harmful, equivalent to placebo, or free of risk. A more complete interpretation would require the analysis methods, uncertainty estimates, outcome completeness, and participant-level event information, none of which are reported in the registry record.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between counting events and counting people who experience events. A participant can potentially experience multiple events, so a total event count may reflect recurrence as well as the number of participants affected. The registry reports both a primary event count and a separate summary of participants affected by other adverse events. Keeping these measures distinct is necessary for accurate interpretation.
The posted group sizes are unequal, and the registry does not report a rate or a modeled comparison for the primary count. That makes it important not to treat the event totals as if they were directly comparable measures of individual risk. A sound count analysis may need to account for exposure time, recurrence, and variability among participants; the record does not say how these features were handled.
The trial also illustrates that design labels and outcome data answer different questions. Randomization and double masking describe how the study was organized. They are relevant safeguards, but do not convey the precision of the result. For the primary endpoint, the registry posts arm totals but no comparative estimate or uncertainty interval. Thus, a reader can describe the observations but cannot assess the precision of a treatment contrast from the posted analysis.
Finally, the named secondary outcomes indicate that the study addressed fatigue and blood markers as well as adverse events. Yet their results and analyses are not reported. This makes the distinction between outcomes specified in a record and results that can be interpreted especially important. The statistical value of the record lies in identifying the study question and the limited descriptive results available, while also making clear which inferential conclusions remain unsupported.
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 is brief on analysis details. It does not report a statistical analysis plan, a sample-size justification, an interim analysis, or a method for comparing the primary event counts. It reports 0 analyses and states that values are missing or not estimable for a two-arm comparison. The reason a comparison was not estimable is not reported in the registry record.
Participant-level information is unavailable in the posted results. The record does not show how many participants experienced at least one primary-endpoint event, how events were distributed across participants, whether any participants experienced repeated events, or how long each participant contributed observations. These omissions limit interpretation of event counts and prevent assessment of a count model's assumptions.
The record does not report adherence, withdrawals, protocol deviations, or the completeness of adverse-event reporting. It describes the analysis population as participants enrolled in the treatment period, but does not provide more detailed analysis-population definitions. Missing-data handling is not reported in the registry record.
The registry lists 4 outcome measures, including two named secondary outcomes, but reports no analyses. Results for changes in fatigue scores and blood-marker levels are not reported. The details of the randomization sequence, allocation concealment, and masking roles are also not reported. These limitations concern what can be interpreted from the registry record; they do not establish that the study procedures themselves were inadequate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Oxidative Pathways in MS Fatigue — NCT02804594.
- Registry record last updated 2026-07-30; status last verified 2026-07.
- Results first posted 2020-02-18.
- 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
The completed study, NCT02804594, is a Phase 2 randomized, double-blind, parallel-group, single-center comparison of N-acetyl cysteine and placebo for fatigue in progressive multiple sclerosis. The registry lists enrollment of 15 and describes 4 weeks of treatment. The N-acetyl cysteine regimen was 1250 mg three times daily; placebo was taken three times daily.
The primary outcome was the number of adverse events related to N-acetyl cysteine over 4 weeks. The registry reports 12 events in the N-acetyl cysteine group and 6 in the placebo group, but no estimable two-arm comparison or inferential analysis. Serious adverse events and deaths were reported as 0 in both groups. Two secondary outcomes are named, but their results are not reported in the registry record.