Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension (NCT04908397), a non-randomized phase 1 study. The primary outcome is Plasma Carnitine Concentration.

2. Clinical Question

The registry describes a mechanistic pilot, not a randomized comparison of supplementation with a control treatment. Its stated primary endpoint is a change in a circulating biomarker: plasma carnitine concentration. The study summary also describes aims to assess carnitine intake, stability of plasma carnitine over time, and possible physiologic effects. Those aims are distinct from the primary endpoint and do not, by themselves, establish that any observed biomarker change corresponds to a clinical benefit.

The stated hypotheses concern whether carnitine consumption is reduced in PAH, whether plasma carnitine remains stable over time, and whether supplementation increases circulating carnitine. The registry record gives those as hypotheses to test, not as established findings. It also lists secondary outcomes involving dietary intake, supplement use, six-minute walk testing, functional class, side effects, echocardiography measures, and plasma carnitine stability. Numerical results for these outcomes are not reported in the registry record.

In practical statistical terms, the central question is whether a within-participant biomarker measurement differs between the named visits after supplementation. Without a separate comparator group, the study cannot directly estimate how the same biomarker would have changed over the same period without the intervention. The record therefore supports describing the pilot's question and design, but not drawing a treatment-effect conclusion from the primary endpoint.

3. Trial Design

This is a Phase 1 study listed as non-randomized, unmasked, and single-group. The registry records an enrollment of 10 and identifies L-carnitine as the intervention. The study is marked completed. Its start date is 2021-09-29, and its primary completion date is 2023-06-01. Vanderbilt University Medical Center is listed as the sponsor.

The arm description specifies 500 mg L-carnitine tablets. Participants weighing 50-90kg were assigned a listed dose of 3g/day; those below 50kg or above 90kg were assigned 50mg/kg/day. The frequency is twice a day for 2 weeks. The registry does not report a separate control arm, random allocation, or masking. Consequently, the design does not create a randomized, like-for-like comparison between supplementation and a control condition.

The study summary describes three aims: measuring oral carnitine consumption, assessing stability of plasma carnitine over time, and conducting a mechanistic supplementation pilot. For the stability aim, the summary says plasma carnitine concentration and markers of fatty acid oxidation would be measured at Visit 1 and Visit 2. For the supplementation aim, it describes plasma carnitine as the primary endpoint and lists six-minute walk testing, echocardiography, and plasma markers of lipid metabolism as physiologic assessments.

The primary endpoint description specifies change from Visit 2 (Week 12) to Visit 4 (Week 14), with a timeframe of 2 weeks of intervention. The record does not explain how this endpoint timing relates to all the study aims or provide a detailed visit schedule. It also does not report a statistical analysis plan, a sample-size justification, or whether any interim analyses were planned. Those design details cannot be inferred from the stated phase, enrollment, or intervention regimen.

Because there is one study group, any observed before-and-after change would describe the participants' measurements over time during the intervention period. It would not, on its own, separate an intervention-associated change from other changes occurring over that period. The record's non-randomized, single-group structure is therefore central to interpreting the scope of the study.

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: Single arm study

Overall Study

Reasons for not completing this period:

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 Plasma Carnitine Concentration, measured over 2 weeks of intervention.

The primary endpoint is plasma carnitine concentration, measured in uM. The registry defines the outcome as change from Visit 2 (Week 12) to Visit 4 (Week 14), over 2 weeks of intervention. It specifies the median and inter-quartile range as the summary approach. The numerical values for the endpoint and its change are not reported in the registry record.

Plasma concentration is used as a mechanistic measure because the study summary asks whether supplementation can increase circulating carnitine. In general, a biomarker endpoint can indicate whether a biological quantity changed, but it does not automatically establish a change in symptoms, function, or other clinical outcomes. That distinction matters in this study: the stated primary endpoint is a blood concentration, while functional and physiologic measures appear among the other listed outcomes.

The median describes the central position of observed values when ordered, while the inter-quartile range describes the spread of the middle portion of those values. In general, these summaries can be useful when a distribution is skewed or when a small study makes extreme observations influential. The registry record does not report the participant-level values, the median change, the inter-quartile range for change, or an uncertainty interval for the primary endpoint.

The two named visits provide a within-study time contrast, but no untreated or control-group contrast is specified. The endpoint can therefore address whether measurements differed between those visits among participants in the study. It cannot, without a comparator or additional assumptions, isolate the effect attributable to supplementation from all other explanations for a temporal difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study records outcomes in one group without a separate control group. When an outcome is measured at different visits, the basic contrast is within the group over time. For this trial, the primary endpoint is defined as a change in plasma carnitine concentration from Visit 2 (Week 12) to Visit 4 (Week 14). Such a contrast describes temporal change among the participants measured; it is not the same as a randomized estimate comparing supplementation with no supplementation.

Randomization is a method for assigning participants to study groups in a way intended to support a fair comparison. The registry lists this trial as non-randomized and single-group. There is no separate comparator reported. Accordingly, the record does not support a randomized comparison, and a temporal change cannot automatically be attributed to the intervention. The registry also lists no masking. Masking, in general, can reduce the influence of expectations on some aspects of measurement or reporting, but the record does not state that masking was used.

Why report a median and inter-quartile range?

The primary endpoint is summarized using a median and inter-quartile range. In general, the median is the middle value after observations are ordered, and the inter-quartile range describes the spread between the middle portions of the distribution. These summaries are less dependent on extreme values than the mean and standard deviation. Their use does not imply that the data were skewed; the registry record does not explain why this summary was selected.

For a change endpoint, interpretation depends on how the change was calculated and summarized. The record states that the outcome is change from Visit 2 to Visit 4 and identifies the median and inter-quartile range, but does not give a detailed calculation procedure or numerical results. The record therefore does not allow readers to check how individual values contributed to the summary or how uncertain the estimate is.

What does the endpoint say about mechanism?

As a general concept, a biomarker can help assess whether a biological process or intermediate measure changed. Plasma carnitine concentration is the stated primary endpoint because the study aims to test whether supplementation increases circulating carnitine. A measured increase would address that biomarker question, but would not alone establish improved right-ventricular function, walking ability, or another clinical outcome. Conversely, clinical outcomes listed as secondary measures do not replace the primary biomarker endpoint.

The study summary describes the intervention as a mechanistic pilot and mentions six-minute walk testing, echocardiography, and plasma markers of lipid metabolism as physiologic assessments. It also describes an aim to measure dietary carnitine consumption and an aim to assess stability of plasma carnitine over time. These are related but distinct questions. The registry does not report numerical outcomes for these assessments, and it does not provide results that would establish how they relate to the primary endpoint.

How should uncertainty be considered?

In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the data and the method used; it is not a guarantee that the true value lies in that range. The registry record does not report a confidence interval for the primary endpoint or a test result for the change. Consequently, neither statistical precision nor compatibility with a range of possible effects can be assessed from the registry information.

A small enrollment can make estimates sensitive to individual observations. This is a general consideration, not evidence that any particular observation had an unusual influence in this study. The record gives an enrollment of 10, but does not provide participant-level results or missingness information with which to assess the stability of the summaries. A median and inter-quartile range describe the observed distribution; they do not remove uncertainty arising from a limited amount of data.

What do the registry analysis entries tell us?

The registry lists no analysis entries. That means the registry record does not present an analysis result through those entries; it does not establish that no analysis was conducted outside the registry. A formal statistical analysis plan, including the model, test, confidence-interval method, handling of repeated measurements, and prespecified covariates, is not reported in the registry record. Those choices should not be guessed from the outcome summary or study design.

The study record lists 8 outcome measures and identifies one primary endpoint, alongside secondary outcomes. In general, when multiple outcomes are examined, the chance of at least one apparently unusual result can rise if each is tested separately without accounting for multiplicity. Methods such as a prespecified outcome hierarchy or adjusted testing can address that issue, but no such strategy is reported in the registry record. The available information does not establish whether multiplicity was considered in the investigators' analyses.

Similarly, the record does not state how repeated measurements or incomplete visits were handled, whether an analysis population was defined, or whether the endpoint analysis followed an intention-to-treat or other principle. These are important details for interpreting an estimate, but absence from the registry record is not evidence about what was done outside it. No sample-size justification is reported. Any sample-size planning illustration should be understood as planning information and not as observed power or evidence of an actual treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary plasma carnitine concentration endpoint and secondary outcomes covering intake, function, side effects, echocardiography, and carnitine stability. The record does not report a multiplicity strategy, such as a hierarchy among outcomes, an adjustment to significance thresholds, or a distinction between confirmatory and exploratory analyses. In general, examining multiple outcomes can increase the chance of a positive-looking result arising by chance when each is assessed separately. Without a reported strategy, the inferential status of any secondary findings cannot be established.

The registry record lists no analysis entries. A detailed statistical analysis plan is not reported, including the planned model or test, uncertainty estimates, treatment of repeated measurements, and any covariate adjustment. A sample-size justification is also not reported. These omissions mean that the analysis methods and their prespecification cannot be evaluated from the registry record.

Missing-data methods and the amount or pattern of missing data are not reported in the registry record. It does not state whether all participants completed both visits relevant to the primary endpoint, how incomplete measurements were handled, or whether any imputation was used. The analysis population is also not reported: the record does not specify which participants or measurements were included in each outcome analysis.

These gaps do not establish that the investigators failed to plan or conduct such procedures. They mean only that the registry record does not report them. Because the primary endpoint result itself is also not reported, readers cannot assess the numerical estimate, its precision, the analysis population behind it, or the effect of missing measurements.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (10.0%), pericardial effusion (10.0%).

The registry lists safety information for the Supplement group. Serious adverse events affected 1 participant among 10 at risk; other adverse events affected 3 among 10 at risk. The record also lists 1 death. Chest pain and pericardial effusion are each named as serious adverse event terms, with each term listed at 10.0%.

These figures describe events recorded in the registry, not a comparison of rates between treatment groups. The study is single-group and has no separate comparator reported, so the safety counts do not estimate how event frequency differs from a control condition. The registry record does not report whether the serious events or death were considered related to L-carnitine, nor does it give contextual details about timing, cause, or clinical course. Causality should not be inferred from an event's appearance in the safety record.

Serious adverse events and other adverse events are distinct categories in the record. The listed counts should not be combined or treated as a complete account of all event details. The registry does not provide further event-level information or explain the relationship between the listed serious terms, the participant affected, and the death. These safety figures should therefore be read as descriptive reports from a small pilot, with limited context for attribution or comparison.

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

The registry record identifies a focused mechanistic question: whether L-carnitine supplementation changes plasma carnitine concentration over the stated 2-week intervention period. It provides the study design, intervention description, endpoint definition, and some safety counts. It does not report the numerical result for the primary endpoint. Therefore, it is not possible to state from the registry record whether plasma carnitine increased, decreased, or remained unchanged.

Even if a numerical before-and-after change were available, the single-group, non-randomized design would limit the conclusions that could be drawn about causation. In general, change over time can arise from several factors, and a concurrent comparator helps distinguish intervention-associated change from other influences. This record reports no such comparator. Its design is consistent with a pilot aimed at measuring a mechanistic outcome, not with a controlled estimate of the intervention's effect.

The primary endpoint is a biomarker rather than a direct measure of function or symptoms. The registry lists other outcomes, including six-minute walk testing, WHO Functional Class, echocardiography measures, and side effects, but their numerical results are not reported. The study summary's stated hypotheses and aims are not findings. Neither a proposed pathway nor an intention to assess physiologic effects demonstrates that those effects occurred.

The safety record includes serious adverse events and a death, but does not report causal attribution or enough context to interpret those events in relation to the supplement. The absence of a comparator also limits safety comparisons. The counts are important descriptive information, yet they do not establish whether an event was caused by the intervention.

In general, a pilot can contribute information about measurement and biological plausibility, while leaving uncertainty about effects and their precision. For this trial, the registry record does not provide the primary endpoint estimate, an uncertainty interval, or a detailed statistical analysis plan. It therefore cannot support a conclusion about the size or precision of a biomarker change, or about effects on clinical outcomes. The record's value is in defining the mechanistic question and documenting the design and reported safety information, while leaving the primary numerical result unresolved in the registry.

13. Why This Trial Matters Statistically

This trial matters statistically because its design illustrates the difference between a mechanistic measurement and a comparative treatment-effect estimate. The primary question concerns plasma carnitine concentration across two visits during an intervention period. That can describe change within the study group, but a single-group design does not supply a randomized control contrast. Readers need that distinction to avoid treating temporal change as a causal estimate.

The endpoint also highlights the role of outcome type. Plasma carnitine concentration is a biological measure that addresses a stated mechanistic hypothesis. The registry separately lists functional and physiologic outcomes. In general, a change in an intermediate measure does not automatically imply a change in how participants feel or function. Keeping these outcome domains separate is important when interpreting a pilot study.

The study's enrollment of 10 and use of a median with inter-quartile range make precision and individual observations relevant considerations. The record does not report the primary numerical result or an uncertainty interval, so the estimate's stability cannot be assessed. General statistical reasoning cautions against treating a small pilot as definitive, particularly when the analysis methods, missing-data handling, and multiplicity strategy are not reported.

Finally, the registry's missing primary result demonstrates why design information and outcome reporting answer different questions. Knowing the endpoint definition and schedule clarifies what investigators intended to measure; it does not reveal what was observed. The record permits a careful account of the study's scope and limitations, while its unreported numerical findings prevent an assessment of the primary biomarker change.

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 for interpretation is that the registry record does not report the numerical result for the primary endpoint. It therefore does not show the median change, its inter-quartile range, or an uncertainty estimate. Numerical results for the listed secondary outcomes are also not reported in the registry record, limiting assessment of the broader aims described in the study summary.

The design is single-group, non-randomized, and unmasked, with no separate comparator reported. Any measured change between visits would be descriptive of the study group over time; the design does not provide a randomized comparison that isolates change associated with supplementation. No causal attribution can be made from the design description alone.

The registry records enrollment of 10, but does not report a sample-size justification, statistical analysis plan, missing-data approach, or analysis population. It does not state whether all participants had the measurements needed for the primary endpoint or how incomplete observations were handled. The registry lists no analysis entries, so the methods used to produce inferential results cannot be evaluated from those entries.

The study has several aims and outcome measures, but a multiplicity strategy is not reported. The record also does not explain the rationale for the median and inter-quartile range, the handling of paired measurements, or any adjustment for other factors. These details are not available for assessing robustness or prespecification.

For safety, the registry lists serious events, other events, and a death, but does not report attribution to the intervention, event timing, or clinical context. The lack of a comparator further limits interpretation of event frequency. These specific reporting gaps constrain what can be concluded from this registry record; they do not establish what information may be available outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension — NCT04908397.
• Registry record last updated 2025-09-30; status last verified 2025-09.
• Results first posted 2025-02-13.
• 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 identifies NCT04908397 as a Phase 1 study titled “Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension,” sponsored by Vanderbilt University Medical Center. It is listed as completed, with a start date of 2021-09-29 and primary completion date of 2023-06-01. Enrollment is recorded as 10.

The study is non-randomized, unmasked, and single-group. Its intervention is L-carnitine, and its primary endpoint is plasma carnitine concentration, summarized as a median and inter-quartile range, with change defined from Visit 2 (Week 12) to Visit 4 (Week 14). The stated intervention period is 2 weeks.

The registry lists safety counts, including 1 serious adverse event affected participant among 10 at risk, 3 participants affected by other adverse events among 10 at risk, and 1 death. It does not report the numerical primary-endpoint result, a detailed analysis plan, missing-data methods, or causal attribution for the safety events. The record therefore describes the study's purpose and structure but does not establish the size or precision of a biomarker change.