The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects (NCT03565328), a na phase 2 study. The primary outcome is Number of Participants Who Had Enhancement of Mitochondrial Function in Skeletal Muscle.

2. Clinical Question

This is therefore a question about within-participant change during and after supplementation, not a comparison of NR against placebo or usual care. A single-group design can describe changes over time, but without a concurrent comparison group it cannot separate an intervention-associated change from other explanations, such as natural variation or changes occurring during study participation. The record does not report an outcome estimate, so it cannot establish whether mitochondrial function changed in the participants.

3. Trial Design

The registry identifies this as a phase 2 pilot study of nicotinamide riboside in people with heart failure. It was an open-label, single-group study: masking was listed as none, allocation as NA, and the model as single group. There was no like-for-like control arm. The intended participants were adults ages 18-70 with clinically stable systolic heart failure.

The study planned repeated assessments, including skeletal muscle NMR spectroscopy at baseline, at the end of the 12-week NR supplementation period, and after a 4-week post-NR washout. The brief description also lists screening procedures, blood and urine tests, an echocardiogram, skin sampling, and cardiopulmonary exercise testing. It describes 8 study visits over 16 weeks. These details describe the planned procedures; the registry does not report that every planned assessment was completed.

NR was planned to start at 500 mg daily (250 mg BID), increase at two weekly intervals, and reach 1000 mg PO BID (2000 mg/day). The registry reports 2 participants signed informed consent: 1 subject completed the study and 1 failed screening. The study status is terminated, with lack of enrollment cited as the reason. The record states that this prevented analysis of the primary and secondary outcomes.

The registry does not report a control group, a statistical analysis plan, or a sample-size justification for the trial. The available design information is therefore enough to describe the intended intervention and repeated-measures approach, but not to reconstruct how the investigators planned to analyze outcomes or to assess whether the design could answer a comparative treatment question.

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: 2 participants signed informed consent: 1 subject completed the study; 1 subject failed the screening. Study was terminated due to lack of enrollment and precluded analysis of primary or secondary outcomes.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 2 participants signed informed consent: 1 subject completed the study; 1 subject failed the screening. Study was terminated due to lack of enrollment and precluded analysis of primary or secondary outcomes.

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 Who Had Enhancement of Mitochondrial Function in Skeletal Muscle, measured over baseline-12 week-16 week.

The primary endpoint was the number of participants who had enhancement of mitochondrial function in skeletal muscle. The planned assessment used nuclear magnetic resonance (NMR) spectroscopy at baseline, at the end of the 12-week NR supplementation period, and after a 4-week post-NR washout. This endpoint focuses on a physiological measure in skeletal muscle rather than a direct comparison of clinical events between treatment groups.

In general, repeated measurement can describe whether a participant's measured value changes over time. A baseline assessment offers a reference for later measurements, while a later assessment can show whether a change is present at that follow-up. A post-washout assessment can describe measurements after supplementation has ended. These features explain why repeated assessments may be useful for studying a biological response; they do not establish that a measured change was caused by the intervention.

The registry does not report a primary endpoint result or an analysis of change. It states that the study was terminated because of lack of enrollment and that primary and secondary outcome analyses were precluded. Consequently, the record does not establish how many participants met the endpoint definition, the size or direction of any change, or the precision of an estimate. The endpoint's planned measurement schedule should not be mistaken for a reported finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several design and analysis concepts help clarify what this registry record can and cannot answer. The points about statistical concepts below are general explanations; the analysis plan itself is not reported in the registry record.

What does a single-group design estimate?

A single-group study follows participants receiving an intervention and may describe measurements at different times. When outcomes are available, investigators can report within-participant changes or summarize group measurements at follow-up. Such descriptions do not, by themselves, estimate how outcomes would have differed under a comparator condition. A concurrent control group helps distinguish changes associated with the intervention from changes that might also occur without it. This trial is described as single group, with allocation listed as NA, and no comparator group is reported.

Repeated measurement can be valuable when the research question concerns a changing biological measure. Baseline and follow-up assessments allow a within-participant comparison, while a later measurement after washout can describe the measure after supplementation has stopped. But timing alone does not establish the cause of a difference. Measurement variability, changes in participants' health, and other time-related influences may also affect observed values. These are general considerations, not reported explanations for this study.

What would an endpoint estimate mean?

An endpoint estimate summarizes the outcome according to a defined measurement and analysis. For a count of participants meeting a criterion, interpretation depends on the criterion, the participants included, and how missing assessments are handled. For a continuous measure, interpretation usually depends on the measurement scale and the summary used. The registry describes a primary outcome as the number of participants with enhancement of mitochondrial function in skeletal muscle, with NMR assessments planned at baseline, at the end of supplementation, and after washout. It does not report an analyzed value, the definition of enhancement, or an analysis result.

In general, statistical uncertainty is conveyed by an interval estimate, such as a confidence interval. The interval indicates which effect values are reasonably compatible with the data under the model and assumptions used. An interval's width reflects precision, not whether a result is clinically important. No primary estimate or confidence interval is reported in the registry record, so these features cannot be evaluated for this outcome.

Why does a comparison group matter?

In a randomized comparison, treatment assignment creates groups intended to be comparable in expectation, allowing a difference in outcomes to estimate a treatment contrast under the design and analysis assumptions. In a single-group study, a before-and-after contrast has no parallel untreated or alternative-treatment trajectory. It can describe what happened over time in the observed participants, but it cannot isolate the intervention's contribution. This distinction remains important even when a biological measure is objective or repeatedly assessed.

The registry identifies masking as none. In general, lack of masking can affect outcomes that involve judgment or participant reporting; it may also shape behavior or study procedures. The record does not report whether masking was considered in the statistical plan, and no outcome analysis is available to assess its influence.

How should planning calculations be read?

In general, a sample-size calculation asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen probability of statistical significance. Its output depends on the assumed effect, variability, significance level, allocation, and analysis method. It is a planning aid, not a measure of the probability that a completed trial's result is true. The registry describes sample-size figures as planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also distinguishes illustrations for time-to-event outcomes from those for other outcomes.

Those calculations are not the trial's design justification, and the statistical plan is not reported in the registry record. They should not be described as observed power. The registry also says that outcome analyses were precluded, so the record does not provide a primary endpoint estimate alongside which to judge a treatment effect. Planning assumptions cannot replace that missing analysis or turn this single-group study into a comparative trial.

What is over-dispersion, in general?

For count outcomes, a statistical model may assume that variability follows a particular pattern. Over-dispersion means that the observed variability is greater than the model assumes. If it is ignored, estimated uncertainty can be too small, making results appear more precise than warranted. Appropriate methods can account for extra variability, but the choice depends on the outcome and design. The registry does not report an analysis model for the primary endpoint, and no such model should be inferred from the endpoint description alone.

For this record, the key methodological fact is not a particular test or model: it is that the study was terminated for lack of enrollment and the registry says analysis of primary and secondary outcomes was precluded. The statistical analysis plan, handling of missing outcome data, and analysis populations are not reported in the registry record. As a result, there are no reported inferential estimates to evaluate for model choice, uncertainty, or robustness.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes, but a statistical plan explaining how they were to be analyzed is not reported in the registry record. In particular, the record does not report whether investigators planned to adjust for testing multiple outcomes, define a hierarchy among outcomes, or treat secondary analyses as exploratory. In general, when multiple hypotheses are tested, the chance of at least one apparently notable result can rise; a prespecified approach helps readers understand how results should be interpreted. No outcome analyses are reported, so multiplicity cannot be assessed from observed results.

The registry states that 2 participants signed informed consent: 1 completed the study and 1 failed screening. It also states that lack of enrollment led to termination and precluded analysis of primary and secondary outcomes. The distinction between screening failure and missing follow-up data matters: a person who failed screening is not described as a participant completing outcome assessments. The record does not report which measurements were obtained for the participant who completed the study, or whether any planned measurements were missing.

Analysis populations, such as an intention-to-treat population or a population defined by treatment exposure, are not reported in the registry record. Nor are missing-data methods, rules for excluding measurements, or imputation procedures. Those omissions mean that an analysis set cannot be reconstructed and no assumptions about missing outcomes should be made. The reported completion and screening information describes study disposition; it does not provide a basis for calculating an outcome effect or filling in unreported 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 0% reporting threshold.

The registry lists 0 serious adverse events among 1 participant at risk, 0 other adverse events among 1 participant at risk, and 0 deaths in the nicotinamide riboside group. These are descriptive counts for the safety reporting recorded in the registry. The record does not list serious adverse-event terms.

In general, an adverse-event count describes events recorded during the defined observation and reporting period; it does not by itself establish whether an event was caused by an intervention. A zero count means no events of that category were recorded in the stated at-risk group. It does not demonstrate that the intervention is free of risk, particularly when exposure and follow-up are limited.

The study was terminated because of lack of enrollment, and the registry reports 1 participant completed the study. The adverse-event figures should therefore be interpreted as sparse descriptive information, not as a precise estimate of safety or a comparison with another treatment. The registry does not report a control group against which these counts could be contrasted.

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

The record establishes that a pilot study was planned to assess skeletal muscle mitochondrial function during NR supplementation and after washout in people with stable systolic heart failure. It also establishes that the study was terminated due to lack of enrollment. The registry reports that 2 participants signed informed consent, 1 completed the study, and 1 failed screening; it explicitly states that primary and secondary outcome analyses were precluded.

As a result, the registry does not report whether the primary endpoint was met, how mitochondrial function changed, or whether any secondary outcome changed. It does not provide an effect estimate or its uncertainty. The absence of an analyzed result is not evidence that there was no effect; it means the record does not provide an analysis from which an effect can be estimated.

The study's single-group design is also important. In general, a measured change over time among participants receiving an intervention is not the same as a controlled treatment effect. Without a concurrent comparator, other explanations for change cannot be separated from the intervention. Since the registry reports no comparative arm and no outcome analysis, it cannot answer whether NR performs better than placebo, usual care, or another intervention.

The safety counts are likewise limited. They describe the events recorded in the registry, but the small reported exposure and absence of a control group do not permit a precise comparative safety assessment. The counts should not be treated as proof that adverse events cannot occur.

Any planning illustrations associated with the record should be understood as hypothetical calculations under stated assumptions, not observed power or evidence of efficacy. The central result is therefore a limitation of evidence: the planned outcome questions remain unanswered in the registry because the study did not produce reported primary or secondary analyses.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between a research question and an answer supported by analyzed data. The registry describes a biological question about skeletal muscle function, specifies repeated NMR assessments, and identifies a primary endpoint. But the study was terminated due to lack of enrollment, and the registry says that analysis of primary and secondary outcomes was precluded. A planned measure is not an observed result.

The record also highlights why study design shapes interpretation. A single-group study can be useful for describing feasibility, procedures, or observed changes, but it does not provide a randomized treatment contrast. Even a clear change from baseline would not alone show that NR caused it. In this record, there is no reported outcome estimate to describe in the first place.

Small and incomplete enrollment has implications beyond precision. It can limit the information available about whether assessments were completed, how outcomes vary, and whether a reliable analysis is possible. Here the registry reports 1 participant completed the study and 1 failed screening. It does not report outcome estimates or uncertainty intervals, so readers cannot judge the magnitude or precision of any change.

Finally, planning calculations and safety counts require careful interpretation. Sample-size illustrations are conditional on assumptions and are not observed power. Safety counts are descriptive and do not establish absence of risk. The record is a useful example of why statistical interpretation depends on the actual design, outcome data, analysis plan, and uncertainty—not merely on the presence of a planned endpoint or a numerical calculation.

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 central limitation is that the registry reports no primary or secondary outcome analyses. It states that the study was terminated due to lack of enrollment and that this precluded analysis. Therefore, there is no reported estimate of skeletal muscle mitochondrial function, no reported estimate of change over time, and no reported precision measure for the primary endpoint.

The study was designed as a single-group investigation, with no comparator arm. This prevents a controlled estimate of the difference between NR and another treatment condition. The registry also lists masking as none. These design features should be kept in view when interpreting the intended research question, even though outcome analyses are unavailable.

Enrollment was limited: 2 participants signed informed consent, 1 completed the study, and 1 failed screening. The registry does not report which planned assessments were completed by the participant who finished the study, how missing measurements were handled, or what analysis population was intended. The statistical analysis plan and sample-size justification are not reported in the registry record.

The registry describes multiple secondary outcomes, but does not report a multiplicity strategy or results for those outcomes. It also does not report an endpoint estimate, confidence interval, or model specification. The safety figures are descriptive and come from limited reported exposure; they cannot support a precise risk estimate or comparison. Together, these limitations mean that the record documents the planned investigation and its early termination, but does not provide evidence with which to quantify an outcome effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Nicotinamide Riboside on Skeletal Muscle Function in Heart Failure Subjects — NCT03565328.
• Registry record last updated 2020-10-28; status last verified 2019-11.
• Results first posted 2020-10-28.
• 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

NCT03565328 is a phase 2 pilot study of nicotinamide riboside in people with stable systolic heart failure. The intended design was single group, open label, with repeated skeletal muscle NMR assessments at baseline, at the end of the 12-week supplementation period, and after a 4-week post-NR washout. The planned NR regimen increased from 500 mg daily (250 mg BID) to 1000 mg PO BID (2000 mg/day).

The registry reports 2 participants signed informed consent: 1 completed the study and 1 failed screening. The study was terminated due to lack of enrollment, and primary and secondary outcome analyses were precluded. The registry does not report outcome estimates or an analysis plan. Safety listings show 0 serious events, 0 other events, and 0 deaths in the reported at-risk groups; these counts are descriptive and limited.