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 Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration (NCT03912220), a randomized phase 2 study. The primary outcome is Denervation of Skin.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03912220 |
| Phase | Phase 2 |
| Condition | Small Fiber Neuropathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 45 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Johns Hopkins University |
| Results posted | Yes |
2. Clinical Question
Population
The registry record lists small fiber neuropathy as a condition. Its brief summary describes otherwise healthy study participants in whom small fiber nerve injury was experimentally induced by applying capsaicin to skin. These descriptions identify the clinical context and the study setting; the posted primary result concerns the experimentally induced skin change rather than a reported clinical neuropathy outcome.
Intervention
The intervention was oral nicotinamide riboside. The arm description specifies a dose of 900 mg twice a day. The study was designed to evaluate prevention of capsaicin-induced small fiber nerve degeneration and to assess nerve regeneration, according to the registry summary.
Comparator
The comparator was placebo. The registry describes placebo pills as similar in size and shape to the experimental drug. Participants were assigned to the nicotinamide riboside or placebo arm in a randomized, double-masked, parallel-group design.
Primary question
The posted primary endpoint asks whether the percent change in intraepidermal nerve fiber density after experimental capsaicin denervation differed between the nicotinamide riboside and placebo groups at 2 days. Density was assessed by counting nerve fibers per millimeter of skin in biopsies and comparing the count with baseline. The posted result reports the group medians, full ranges, and a Wilcoxon (Mann-Whitney) comparison. It does not report a confidence interval for the treatment contrast.
3. Trial Design
The registry describes a randomized, double-masked, parallel-group phase 2 trial. Nicotinamide riboside was compared with placebo, and the record marks the trial as completed. Enrollment is reported as 45. The posted primary outcome includes 26 participants in the nicotinamide riboside group and 19 in the placebo group.
The study dates in the registry record are a start date of 2020-09-01 and a primary completion date of 2023-05-01. These dates describe the registered study timeline; they do not by themselves explain how recruitment, follow-up, or analysis proceeded. Further details of those processes are not reported in the registry record.
The intervention was nicotinamide riboside taken orally at 900 mg twice a day. The comparator was a placebo oral tablet described as similar in size and shape to the experimental drug. The brief summary says capsaicin was applied to skin to experimentally induce nerve denervation. It also states that nerve regeneration would be evaluated, but the posted primary result addressed denervation.
The registry lists 2 outcome measures and 2 analyses. One posted analysis compares the primary outcome between the treatment groups. The record does not report the allocation procedure beyond randomization, the masking roles, the intended analysis population, or further protocol details. Those omissions limit how fully the design can be reconstructed from the registry record alone.
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.
Overall Study
| Stage | Nicotinamide Riboside | Placebo |
|---|---|---|
| STARTED | 26 | 19 |
| COMPLETED | 26 | 19 |
| NOT COMPLETED | 0 | 0 |
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 | Nicotinamide Riboside | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 26 | 19 | 45 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 26 | 19 | 45 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 11 | 7 | 18 |
| Sex: Female, Male: Male | Participants | 15 | 12 | 27 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 4 | 4 | 8 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): White | Participants | 20 | 14 | 34 |
| 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 | 26 | 19 | 45 |
| Baseline intraepidermal nerve fiber density | fibers/mm | 10.75 (SD 5) | 11.1 (SD 3.9) | 10.9 (SD 4.5) |
6. Primary Endpoint
The registry lists the primary outcome as Denervation of Skin, measured over 2 days.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | percent change |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is denervation of skin, expressed as percent change. The registry describes examining the loss of intraepidermal nerve fibers after capsaicin-induced denervation. Skin biopsies were stained for a pan-axonal marker, and the number of intraepidermal nerve fibers per millimeter of skin was counted and compared with a baseline biopsy to determine percent change in density. The assessment timeframe is 2 days.
In general, measuring nerve fiber density provides a biological measure of the local skin-nerve change targeted by this experimental injury model. Comparing the follow-up count with a baseline count expresses change relative to each participant’s starting measurement rather than reporting only a follow-up count. This is the rationale for using a change endpoint; it does not establish that the measure represents symptoms, function, or longer-term outcomes.
The registry reports the primary endpoint as a median with a full range. It does not report an endpoint confidence interval or a separate clinical interpretation threshold. The posted result should therefore be read as a comparison of the measured biopsy-based changes at the stated timeframe, not as a direct measure of clinical benefit.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median percent change in intraepidermal nerve fiber density is 0.1 in the nicotinamide riboside group and 0.1 in the placebo group. The full range is 0.0 to 0.8 for nicotinamide riboside and 0.0 to 1.0 for placebo. These summaries show identical reported medians and ranges that overlap. A median describes the center of the observed values; the full range describes the lowest and highest values reported, not the precision of a treatment-effect estimate.
The registry reports a Wilcoxon (Mann-Whitney) superiority analysis with p = 0.33. This test compares the distributions of the observed values between groups using their ranks. It does not directly estimate a difference between medians, and its p-value does not quantify the size of a treatment effect. The registry record does not report a confidence interval for the between-group effect, so the precision and range of plausible effect values cannot be assessed from a posted interval.
In general, a p-value describes how compatible the observed data are with a specified null model under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it measure the probability that an intervention will or will not have an effect. The record does not state a decision threshold for the sponsor’s primary analysis, so the reported p-value should be read as the test result rather than as a complete account of the analysis plan.
The posted summaries do not indicate a separation between the groups in their medians. However, that observation alone does not establish equivalence or exclude differences that the available data could not estimate precisely. The result is specific to this endpoint, experimental injury model, and 2-day timeframe. The record does not report a primary-outcome confidence interval, individual observations, or enough detail to evaluate the sensitivity of the result to analysis choices.
The registry lists 26 participants in the nicotinamide riboside arm and 19 in the placebo arm for this outcome. These are the posted group counts; they should not be taken to establish how missing observations were handled or which analysis population was used. Those details are not reported in the registry record.
9. Statistical Methods Explained
The primary comparison uses the Wilcoxon (Mann-Whitney) method. The registry reports each group’s outcome as a median and full range, which is a descriptive presentation. The rank-based test is a separate inferential procedure: it orders the observed outcomes and assesses whether their ranks tend to differ between groups. It does not require the analysis to be framed as a comparison of means, and it is often used when a normal-distribution model for the outcome is not appropriate. This is general statistical context; the registry record does not explain why this method was selected for this trial.
What does the median describe?
In general, the median is the middle of the ordered observations. It provides a measure of the center that is less influenced by extreme values than the mean. Here the reported median percent change is 0.1 in each group. Identical medians do not mean that every participant had the same outcome, nor do they show that the full distributions were identical. The reported full ranges extend from 0.0 to 0.8 for nicotinamide riboside and from 0.0 to 1.0 for placebo. A range reports the endpoints of the observed values but does not show how densely values are distributed between them.
What does the rank test assess?
In general, the Mann-Whitney test compares the relative ranks of observations across groups. Its interpretation is not automatically a test of equality of medians. A location-shift interpretation requires additional assumptions about the shapes of the group distributions. The registry does not report distributional diagnostics or an explanation of the test’s intended estimand. The reported p-value is 0.33; without a reported effect estimate and confidence interval, it cannot describe the size or precision of a between-group difference.
How should the p-value be read?
In general, a p-value is calculated under a null model and describes how unusual a result at least as extreme as the observed result would be if that model held. It does not give the probability that the null model is correct. Nor does a larger p-value prove that groups are equivalent. Interpretation depends on the analysis plan, study design, endpoint quality, and estimate precision. The registry record reports the test and p-value but does not report a confidence interval or the decision threshold for that test.
What do randomization and masking contribute?
In general, random assignment is intended to make treatment groups comparable with respect to measured and unmeasured characteristics on average. Double masking is intended to reduce the influence of treatment knowledge on participants’ experiences and on study conduct or assessment, depending on which roles are masked. The record identifies the study as randomized and double-masked, but does not describe the randomization sequence, concealment procedures, or exactly who was masked. These design labels therefore convey useful information without providing the full operational details.
What is the role of the planning illustration?
The registry’s stated planning assumptions describe an illustration based on the observed effect, not the trial’s own design justification. The assumptions specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study was designed around those assumptions. The record does not report the original sample-size justification, and no planning result should be interpreted as a description of the trial’s actual achieved power.
What can the posted analysis establish?
The analysis describes the observed primary endpoint and reports a rank-based comparison. It does not provide an estimate with a confidence interval, establish equivalence, or address outcomes beyond the registered measure and timeframe. General statistical interpretation distinguishes the evidence against a null model from the magnitude and precision of an effect. In this case, the registry record contains a p-value and descriptive summaries, but not an interval that would show how uncertain an estimated contrast is. Further analysis details, including missing-data handling and the analysis population, are not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Wilcoxon (Mann-Whitney) | not reported | 0.330 |
The registry reports the sponsor’s primary comparison as a Wilcoxon (Mann-Whitney) superiority analysis, with p = 0.33. The group medians are both 0.1, and the full ranges are 0.0 to 0.8 for nicotinamide riboside and 0.0 to 1.0 for placebo. The record does not report a sponsor-estimated treatment contrast or its confidence interval.
The registry record does not flag a discrepancy between the reported analysis and a recalculation. It also does not report a separate recalculated effect estimate or interval that could be compared numerically with the sponsor’s result. Accordingly, the sponsor’s reported test and descriptive summaries are the available inferential results. A comparison of numerical estimates cannot be made from the registry record alone.
The distinction matters because a recalculation from posted summary statistics, when available, would be a simple unadjusted analysis and might not reproduce the sponsor’s full analysis choices. The reported test is the sponsor’s analysis as recorded; the registry does not provide additional details about covariate adjustment, analysis population, or missing observations. These details should not be inferred from the p-value.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 2 analyses, but only the primary outcome result is described with a group comparison in the posted results. The record indicates that values for the other endpoint are missing or not estimable for a two-arm comparison. Its result therefore cannot be interpreted as evidence for or against a treatment-group difference.
Multiplicity arises when several outcomes, timepoints, or comparisons are tested, because the chance of at least one nominally unusual result can increase as tests accumulate. In general, an analysis plan may address this through a prespecified hierarchy or statistical adjustment. The registry record does not report whether any multiplicity strategy was planned or used. The count of registered outcomes alone does not reveal which outcomes were considered confirmatory or how their testing was organized.
Missing-data methods, reasons for missing or non-estimable results, and the handling of incomplete observations are not reported in the registry record. The record also does not identify the analysis population or state whether the posted group counts include all randomized participants or only those contributing outcome data. Therefore, the reported arm counts cannot by themselves establish the extent or treatment-group pattern of missingness.
The registry does not report a protocol-level statistical analysis plan, interim analyses, or the sponsor’s approach to selecting outcomes for analysis. Those details should not be assumed. The primary result can be read as the reported comparison for the posted endpoint, while its relationship to other registered outcomes and any missing data remains uncertain.
12. 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 |
|---|---|---|---|
| Nicotinamide Riboside | 0 | 26 | 0.0% |
| Placebo | 0 | 19 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nicotinamide Riboside | 0 of 26 |
| Placebo | 0 of 19 |
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 |
|---|---|
| Nicotinamide Riboside | 0 of 26 |
| Placebo | 0 of 19 |
The registry reports 0 serious adverse events among the 26 participants at risk in the nicotinamide riboside group and 0 among the 19 participants at risk in the placebo group. The recorded count for other adverse events is also 0 in each group, and deaths are recorded as 0 in each group. No top serious-event terms are listed.
These figures describe what the registry reports for the stated at-risk groups. They do not provide a detailed account of how events were collected, the observation period for safety, or whether there were events that did not meet the record’s reporting criteria. Such details are not reported in the registry record.
A count of zero in a study group is not proof that an event cannot occur, and these counts alone do not establish comparative safety. The posted figures should be read as event-count summaries for this trial, rather than as a general estimate of risk or a recommendation about treatment.
13. What the Result Does, and Does Not, Mean
The result describes a comparison of biopsy-based percent change in intraepidermal nerve fiber density at 2 days after capsaicin-induced denervation. The posted median was 0.1 in each group, with full ranges of 0.0 to 0.8 for nicotinamide riboside and 0.0 to 1.0 for placebo. The registry’s Wilcoxon (Mann-Whitney) analysis reports p = 0.33. These registry entries summarize the result for this endpoint and timeframe.
The result does not establish that the groups are equivalent. A failure to show a clear separation in this analysis is not the same as evidence that all potentially meaningful differences have been ruled out. The registry does not report a confidence interval for the group contrast, so the precision of an estimated difference cannot be assessed from the reported analysis.
The result also does not answer every question raised by the study summary. The study was intended to evaluate nerve regeneration as well as prevention of experimental denervation, but values for the other endpoint are missing or not estimable for a two-arm comparison in the registry record. The posted result therefore does not provide a comparative conclusion about that endpoint.
The findings are specific to the registered study setting, the capsaicin-induced skin injury model, the measured biopsy outcome, and the 2-day timeframe. They do not directly describe effects on symptoms, daily function, or longer-term nerve outcomes, which are not reported as results in the registry record. The findings should not be generalized beyond the measured outcomes and trial context without further evidence.
14. Why This Trial Matters Statistically
This trial raises several important statistical issues in a compact experimental setting. The primary outcome is a continuous change measure summarized by medians and full ranges, while the reported comparison is rank-based. Readers need to distinguish descriptive summaries from the inferential test: the medians convey the centers of the posted group results, while the test evaluates ranks rather than directly estimating a median difference.
The registry reports the same median in each arm, but that fact alone does not answer whether the underlying distributions differ or how precisely a treatment contrast has been estimated. A confidence interval would help communicate precision, yet one is not reported for the primary comparison. The p-value also cannot stand in for an effect estimate. These distinctions are central to interpreting small clinical studies without treating a single test result as a complete account of evidence.
The experimental endpoint has a defined biological measurement: nerve fiber counts per millimeter of skin, compared with baseline. That clarity supports interpretation of what was measured, but it does not make the outcome interchangeable with clinical symptoms or longer-term outcomes. The timing and endpoint determine the scope of the statistical conclusion.
Finally, the registry’s other endpoint is not estimable for a two-arm comparison, and details of missing data, analysis populations, and multiplicity are not reported. Those omissions matter because they affect how readers understand the completeness and context of the primary result. The record illustrates why transparent estimates, uncertainty intervals, and analysis details are as important as a p-value.
15. 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 gives the primary outcome summaries and a p-value, but does not report a treatment-effect estimate with a confidence interval. The full ranges describe the observed extremes and are not substitutes for an interval around the between-group effect. Without an effect estimate and interval, the size and precision of the comparison cannot be evaluated directly.
The outcome is specific to experimental capsaicin-induced denervation and a 2-day assessment. The record does not report longer-term results for the primary endpoint. Although the brief summary says nerve regeneration would also be evaluated, the other endpoint is described as having values missing or not estimable for a two-arm comparison. This leaves that part of the study question unanswered in the posted results.
Further analysis details are not reported in the registry record, including the analysis population, handling of missing observations, randomization procedures, masking roles, and any multiplicity strategy. The registry also does not report the protocol’s sample-size justification or a detailed statistical analysis plan. These omissions limit assessment of how the reported analysis relates to the intended design and how complete the outcome data were.
The registry lists small fiber neuropathy as a condition while the brief summary describes otherwise healthy participants undergoing experimentally induced skin injury. The posted result is therefore best understood in the experimental context described, not assumed to represent outcomes in a broader clinical population. The record does not provide results for symptoms, function, or other clinical endpoints that would support those interpretations.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration — NCT03912220.
- Registry record last updated 2024-06-12; status last verified 2024-06.
- Results first posted 2024-06-06.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry record describes a completed randomized, double-masked, parallel-group phase 2 trial of oral nicotinamide riboside versus placebo. Enrollment is reported as 45, with a start date of 2020-09-01 and a primary completion date of 2023-05-01.
The primary outcome is percent change in intraepidermal nerve fiber density after capsaicin-induced skin denervation, assessed at 2 days. The reported median is 0.1 in each arm; the full ranges are 0.0 to 0.8 for nicotinamide riboside and 0.0 to 1.0 for placebo. The reported Wilcoxon (Mann-Whitney) p-value is 0.33.
The registry does not report a confidence interval for the primary comparison. Values for the other endpoint are missing or not estimable for a two-arm comparison. Safety counts show 0 serious adverse events, 0 other adverse events, and 0 deaths in each arm as recorded.