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 Altering Lipids for Tolerance of Aromatase Inhibitor Therapy (NCT04268134), a na phase 2 study. The primary outcome is Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04268134 |
| Phase | Phase 2 |
| Condition | Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 77 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with breast cancer receiving aromatase inhibitor therapy. The registry summary describes difficulty tolerating this therapy, including joint pain and stiffness, as the motivation for testing omega-3 supplementation. The record does not report further eligibility details or a more specific description of the participants included in the reported primary outcome.
Intervention
Participants took an oral omega-3 fatty acid supplement daily. The regimen is described as omega-3 ethyl esters in four 1gm capsules, each containing 465 mg eicosapentaenoic acid (EPA) and 375 mg docosahexaenoic acid (DHA). Supplementation began after a period of aromatase inhibitor therapy alone.
Comparator
The design was single-group, with no concurrent comparison arm described. The primary endpoint compares measurements at the start of supplementation with measurements after supplementation. The earlier measurement follows a period of aromatase inhibitor therapy alone, but it is a within-participant time point, not a separate randomized or untreated group.
Primary question
Among participants receiving aromatase inhibitor therapy, how did the mean percentage of total fatty acids in each measured polyunsaturated fatty acid group change from the start of omega-3 supplementation to three months later? The later measurement was taken six months after aromatase inhibitor therapy began. The primary endpoint concerns plasma oxylipins grouped by fatty acid substrate; it is not itself a measure of joint symptoms, treatment discontinuation, or cancer outcomes.
3. Trial Design
This was a completed Phase 2, single-group study sponsored by University of Michigan Rogel Cancer Center. The registry lists enrollment of 77 and study dates from 2020-07-28 to primary completion on 2024-02-27. Allocation is recorded as NA, and masking as none. These design features mean the registry does not describe a randomized, masked comparison between supplement and control groups.
The study sequence included aromatase inhibitor therapy alone for three months, followed by three months of aromatase inhibitor therapy with daily omega-3 supplementation. The primary measurement compares the start of supplementation with the end of that supplementation period. The record therefore describes a before-and-after assessment within one study group, rather than a comparison of separate intervention and control arms.
The primary outcome was a continuous measure: change in the mean percentage of total fatty acids for each polyunsaturated fatty acid group. The registry also lists outcomes concerning fatty acid changes at other time points, development of aromatase inhibitor-associated musculoskeletal symptoms, and discontinuation of aromatase inhibitor therapy due to symptoms or toxicity. It lists six outcome measures and zero analyses. The record does not report the number of participants contributing data to each outcome or explain how the analysis population was defined.
The study’s clinical motivation was the difficulty some patients have tolerating aromatase inhibitor therapy. However, the primary endpoint is a biochemical measure, not a direct symptom or treatment-continuation endpoint. The design can describe changes over time during the study sequence, but the registry does not describe a concurrent control group that would separate the supplement period from other changes occurring over time.
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: 7 patients were enrolled but did not start study treatment
Overall Study
| Stage | Omega 3 Fatty Acid Supplement |
|---|---|
| STARTED | 70 |
| COMPLETED | 50 |
| NOT COMPLETED | 20 |
Reasons for not completing this period:
| Reason | Omega 3 Fatty Acid Supplement |
|---|---|
| Adverse Event | 3 |
| noncompliance | 2 |
| Withdrawal by Subject | 10 |
| Physician Decision | 5 |
Analysis population for the primary outcome, as defined in the registry: The results reported are the change in the previously calculated, but not reported, at the start of the study and at 3 months. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported.
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 | Omega 3 Fatty Acid Supplement |
|---|---|---|
| Participants analysed | 70 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 45 |
| Age, Categorical: >=65 years | Participants | 25 |
| Sex: Female, Male: Female | Participants | 70 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 69 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 1 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 63 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 70 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA, measured over From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Change percentage of total fatty acids |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures the change in the mean percentage of total fatty acids for each polyunsaturated fatty acid group from the start of omega-3 supplementation to three months of supplementation. The first measurement was taken after three months of aromatase inhibitor therapy alone; the second was taken six months after aromatase inhibitor therapy began. The listed groups are based on linoleic acid (LA), arachidonic acid (AA), alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
Blood samples were used to quantify plasma oxylipins, with the registry describing solid phase extraction and liquid chromatography-electrospray ionization tandem mass spectroscopy. For each participant, the percentage for each group was to be calculated at both time points, then summarized as a mean across participants. The endpoint is reported as change in the mean results, with standard deviation identified as the dispersion measure.
This biochemical endpoint can characterize how the measured fatty acid groups changed during the supplementation period. It does not directly measure pain, stiffness, treatment discontinuation, or cancer outcomes. The registry record does not report the numerical mean changes or their standard deviations, so the direction, size, and variability of the observed changes cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a single-group, before-and-after study of omega-3 supplementation during aromatase inhibitor therapy. Its primary endpoint is change in mean percentage of total fatty acids within each polyunsaturated fatty acid group. The record identifies the measurement schedule and the intended summary statistic, but it does not report the numerical results for the primary endpoint. In particular, the registry record does not report the mean changes or standard deviations for the listed groups.
Without those estimates, it is not possible to describe whether the measured percentages increased or decreased, how large any changes were, or how variable the measurements were across participants. The record also does not report confidence intervals or p-values for these outcomes. Consequently, the precision of the estimates and the strength of statistical evidence cannot be assessed from the registry record. The absence of reported values is not evidence that there was no change.
The study’s sequence offers a within-group comparison across time: a measurement after aromatase inhibitor therapy alone and another after a subsequent period with supplementation. Such a comparison can describe what happened between the two measurements in the study group. It does not, by itself, establish that supplementation caused any change. Without a concurrent control group, changes over time cannot be separated from other influences that may have occurred during the same period. This is a design limitation, not a conclusion about the direction or size of the outcome.
The registry lists other outcomes, including development of aromatase inhibitor-associated musculoskeletal symptoms and discontinuation of therapy due to symptoms or toxicity. Their presence indicates that the study addressed clinical outcomes in addition to its biochemical primary endpoint. However, their numerical results are not reported in the registry record for this account, so no event rates, comparisons, or conclusions about those outcomes can be stated.
The record lists 77 enrolled, but does not state how many contributed measurements to the primary endpoint or whether missing measurements affected the analysis. Enrollment should therefore not be treated as the outcome-specific sample size. The safety record separately lists 70 participants at risk. The reason for the difference between that safety denominator and enrollment is not reported in the registry record.
Any sample-size planning illustration associated with the posted results should be read as hypothetical planning rather than as a property of this study’s design or as observed power. The stated illustration assumptions use a two-arm, equal-allocation comparison, while this trial is recorded as single-group. The registry record does not report a statistical analysis plan or a sample-size justification for the trial itself.
9. Statistical Methods Explained
What does a change in the mean represent?
The primary outcome is continuous: for each polyunsaturated fatty acid group, the study calculated a percentage of total fatty acids at two time points and reported the change in the mean. In general, a mean summarizes the average measurement across the participants whose data contribute to an analysis. A change in the mean compares that summary at one time point with the summary at another. It describes a group-level shift; it does not mean that every participant had the same change.
The registry identifies standard deviation as the dispersion measure. In general, standard deviation describes how spread out individual measurements are around their mean. It is not the same as a confidence interval. A standard deviation describes variation among measurements, whereas a confidence interval describes uncertainty around an estimated quantity under a statistical model. The registry record does not report the endpoint standard deviations or confidence intervals, so neither participant-level spread nor estimate precision can be evaluated from the recorded results.
How should the timing be understood?
The primary comparison is between the start of omega-3 supplementation and three months later. The starting measurement was taken after three months of aromatase inhibitor therapy alone, and the later measurement followed three months of aromatase inhibitor therapy with supplementation. This timing gives a before-and-after contrast within the study sequence. It should not be described as a randomized comparison, because the registry records a single-group model and allocation as NA.
In general, repeated measurements in one group can make it possible to describe changes within that group over time. They do not automatically distinguish an intervention effect from time-related changes, changes in other circumstances, or measurement variability. A concurrent control group can help address some alternative explanations, but no such group is described in this record. The registry does not report additional design details that would quantify or resolve these potential influences.
What does the measurement procedure add?
The registry describes blood sampling and quantification of plasma oxylipins using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. The oxylipins were grouped according to PUFA substrate: LA, AA, ALA, EPA, and DHA. The endpoint is therefore a laboratory-based measure organized by substrate group, with a mean percentage calculated for each group at each time point. This measurement is distinct from the separately listed outcomes concerning musculoskeletal symptoms or treatment discontinuation.
The record states that each participant’s percentage was to be calculated at both time points and that the overall study percentage per group would be derived from the mean across participants. It also describes the reported result as change in the mean results. This establishes the general summary being reported, but it does not provide the actual values, the number of observations used for each mean, or details about how incomplete paired measurements were handled.
What can a confidence interval or p-value tell a reader?
General explanation: a confidence interval gives a range of values compatible with an estimate under the assumptions of the analysis. Its width conveys information about precision; a wider interval generally indicates greater uncertainty. A p-value evaluates how compatible the observed data are with a specified null model, under the assumptions of the statistical test. Neither quantity alone establishes clinical importance or causality.
The registry record does not report confidence intervals, p-values, or a statistical test for the primary outcome. It is therefore not possible to judge statistical compatibility with a null value from this record. The lack of those reported statistics should not be replaced with an assumption that a test was or was not significant.
How do the planning illustrations relate to this trial?
General explanation: sample-size calculations estimate how many participants a future study might need under specified assumptions about the effect to detect, the significance level, allocation, and statistical model. They are planning tools, not observed results, and they do not show that a completed trial had a particular probability of detecting an effect. Observed power is not a substitute for reporting an estimate and its uncertainty.
The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe an effect to detect as a stated fraction of the observed effect. The calculations are explicitly planning illustrations rather than the trial’s own design. Because the registry records this study as single-group, the two-arm, equal-allocation assumptions do not describe its actual allocation. The registry record does not report a sample-size justification or statistical plan for the study itself.
The appropriate interpretation of the primary outcome would depend on the estimated changes, their variability, the number of measurements contributing to each estimate, and the analysis method. Those results and details are not reported in the registry record. The design and endpoint definition can be described, but they cannot substitute for the missing outcome estimates.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures, including the primary fatty-acid endpoint and secondary measures concerning fatty-acid changes at other time points, musculoskeletal symptoms, and treatment discontinuation. Multiple outcomes and multiple PUFA groups create more than one opportunity to examine results. In general, when many statistical comparisons are made, the chance of obtaining an apparently notable result by chance can increase. A prespecified analysis plan and a stated approach to multiplicity help readers understand how such results should be interpreted.
The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a broader statistical analysis plan. It lists zero analyses. No adjustment method or confirmatory status should therefore be inferred from the outcome list alone.
Missing-data handling is also not reported in the registry record. The primary endpoint requires measurements at the start and end of supplementation, but the record does not state how many participants had both measurements, how incomplete measurements were handled, or whether any imputation was used. It also does not define an analysis population, such as all enrolled participants or participants with measurements at both time points. Enrollment of 77 does not establish the number analyzed for any particular outcome.
These omissions limit assessment of possible selection effects from missing measurements and the interpretation of multiple outcomes. They do not show that missing data or multiplicity necessarily changed the results; they leave the relevant methods unreported.
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 |
|---|---|---|---|
| Omega 3 Fatty Acid Supplement | 1 | 70 | 1.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Omega 3 Fatty Acid Supplement | 0 of 70 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Omega 3 Fatty Acid Supplement | 0 of 70 |
Most frequent serious adverse event terms
| Event term | Organ system | Omega 3 Fatty Acid Supplement |
|---|---|---|
| Skin infection | Skin and subcutaneous tissue disorders | 1 of 70 |
Serious events with the highest arm-level rate: skin infection (1.4%).
The registry’s serious adverse event record lists the omega-3 fatty acid supplement group with 70 participants at risk. It reports one participant affected by a serious adverse event and zero deaths. The listed serious adverse event term is skin infection, reported as 1.4%. The record separately lists zero other adverse events.
These figures describe what is recorded for this study group; they do not provide a comparison with a control group. The record does not establish whether the serious event was caused by the supplement, and the event listing alone should not be read as establishing causation. It also does not report further details about the event or its timing in the registry record for this account.
The safety denominator of 70 differs from the enrollment figure of 77. The reason for that difference is not reported in the registry record. The denominator should not be assumed to represent the number analyzed for the primary endpoint or for other outcomes. With no concurrent comparator and limited event information, these figures are descriptive safety reporting rather than a comparative estimate of risk.
12. What the Result Does, and Does Not, Mean
The study is relevant to a clinical question about tolerability of aromatase inhibitor therapy and the use of omega-3 supplementation during treatment. Its primary endpoint, however, is a laboratory measure: change in mean percentage of total fatty acids for each PUFA group over the supplementation period. This distinction matters when interpreting what the primary result can address. A biochemical change is not itself evidence of a change in pain, stiffness, treatment continuation, or cancer outcomes.
The registry record does not report the primary outcome values. It is therefore not possible to say whether the measured percentages changed, in which direction they changed, or how precisely the changes were estimated. Nor can the available record support a conclusion about the listed symptom and discontinuation outcomes, because their numerical results are not reported in the registry record for this account.
The single-group sequence can describe measurements before and after supplementation began, but it does not provide a concurrent control comparison. A change across time may reflect the study intervention, other time-related influences, or a combination. The design alone cannot separate these explanations. This is a limitation on causal interpretation, not evidence for or against a particular effect.
The safety record reports one participant affected by a serious adverse event among 70 at risk, lists skin infection at 1.4%, and reports zero deaths and zero other adverse events. Those entries are descriptive. They do not establish a causal relationship or allow a comparative safety assessment.
Overall, the record defines a biochemical endpoint and a treatment sequence, but lacks the numerical outcome estimates and analysis details needed to assess effect size, uncertainty, or clinical relevance. A reader should not interpret absent results as showing either benefit or no benefit.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint and design need to be considered together. The primary outcome is a continuous laboratory measure summarized as a change in mean percentage across several PUFA groups. The study’s clinical motivation concerns tolerability of aromatase inhibitor therapy, but the primary endpoint is not a direct measure of symptoms or treatment discontinuation. Statistical interpretation must keep those distinct outcomes separate.
The single-group sequence also illustrates the difference between describing change and estimating a causal effect. Repeated measurements can show how a study group’s values differ over time. Without a concurrent control group, however, the change cannot be cleanly attributed to the supplement rather than to other influences over the same period. A precise estimate would still not resolve that design limitation on its own.
Reporting the estimate, its variability, and its uncertainty is essential for judging what the observed data can support. Here, the registry identifies the mean and standard deviation as the intended summary but does not report numerical primary results or confidence intervals. As a result, readers cannot assess the magnitude, direction, or precision of the measured changes from the registry record.
The record also demonstrates why planning calculations must be distinguished from trial results and design. The stated planning illustration uses assumptions for a two-arm comparison, whereas the study is recorded as single-group. Such calculations are hypothetical planning aids, not observed power and not evidence that the study detected or failed to detect an 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 primary limitation for interpreting results is that numerical primary outcome estimates are not reported in the registry record. Mean changes and standard deviations are identified as the intended summaries, but their values are unavailable. The record also does not report confidence intervals or p-values. As a result, neither the magnitude and direction of the endpoint changes nor their precision can be assessed.
The single-group, non-masked design has no concurrent control arm described. The before-and-after comparison can characterize change over the study sequence, but cannot by itself distinguish a supplement-related change from other changes over time. The record does not report additional design features that would allow that distinction to be evaluated.
Other important analysis details are not reported in the registry record: outcome-specific sample sizes, missing-data handling, analysis populations, statistical tests, and an approach to multiplicity. The record lists six outcome measures but zero analyses. This prevents assessment of how the reported outcomes were analyzed or how multiple outcomes were treated.
The safety record lists 70 participants at risk, whereas enrollment is 77; the reason for the different figures is not reported. The record also gives limited detail about the serious adverse event. These limits mean the safety entries should be read descriptively, not as a comparative or causal assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Altering Lipids for Tolerance of Aromatase Inhibitor Therapy — NCT04268134.
- Registry record last updated 2026-05-06; status last verified 2026-04.
- Results first posted 2026-05-06.
- 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
NCT04268134, titled “Altering Lipids for Tolerance of Aromatase Inhibitor Therapy,” is a completed Phase 2 study sponsored by University of Michigan Rogel Cancer Center. The registry lists a single-group model, no masking, allocation as NA, enrollment of 77, and study dates from 2020-07-28 to primary completion on 2024-02-27.
Participants received daily omega-3 fatty acid supplementation after a period of aromatase inhibitor therapy alone. The primary outcome was change in mean percentage of total fatty acids for each PUFA group from the start of supplementation to three months later. The registry record does not report the numerical primary outcome results, confidence intervals, p-values, analysis populations, or missing-data methods.
The safety record lists one participant affected by a serious adverse event among 70 at risk, skin infection at 1.4%, zero deaths, and zero other adverse events. The record does not report the reason the safety denominator differs from enrollment.