Pilot Study to Evaluate the Effect of Nicotinamide Riboside on Immune Activation in Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study to Evaluate the Effect of Nicotinamide Riboside on Immune Activation in Psoriasis (NCT04271735), a randomized na study. The primary outcome is Mean Change in the TH17 Cell Cytokine IL-17 Secretion in Response to T-cell Differentiation.

2. Clinical Question

The outcome is a laboratory measure in pg/mL, rather than a measure of psoriasis symptoms or a clinical event. The trial record describes the objective as examining immune function in blood and skin, while the posted primary outcome is specifically the mean change in IL-17 secretion in response to T-cell differentiation. These are related descriptions, but the posted endpoint should be interpreted according to its stated measurement and timeframe.

The record lists 29 participants enrolled and describes the study as randomized, triple masked, and parallel-group. The primary comparison is between the two assigned groups over the period from baseline to Day 28. The record does not report a separate clinical efficacy question or a posted secondary outcome.

3. Trial Design

This was a randomized, triple-masked, parallel-group pilot study. The registry lists the phase as not applicable. The stated study focus was nicotinamide riboside and immune activation in people with mild to moderate psoriasis. Enrollment was 29, and the study status is completed. The record gives a study start date of 2020-08-26 and a primary completion date of 2022-12-19.

Participants were described as people ages 18–80 with mild to moderate active psoriasis who were not currently receiving biological therapy. Screening included medical and medication history, physical examination, body mass index measurement, skin examination, and blood and urine tests. Participants could also have optional skin biopsies from lesions and unaffected skin areas.

The intervention group received nicotinamide riboside chloride 500mg, taken as 2 capsules twice daily by mouth for 28 days. The placebo group took 2 capsules twice daily for the same period. The brief description says participants began the capsules at the first visit and returned for a second visit, with tests repeated. It also describes possible contact between visits and a possible additional visit if side effects occurred after stopping the capsules.

The posted primary outcome compares mean change in TH17-cell IL-17 secretion from baseline to Day 28. The analyzed groups contain 14 participants for nicotinamide riboside and 11 for placebo. The registry identifies one excluded placebo participant because of insufficient T-cells and one excluded nicotinamide riboside participant because of abnormal lipids. Details about the original allocation process, the intended analysis population, and the trial’s original sample-size justification are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: One participant from placebo group not included in analysis due to insufficient T-cells. One participant from Nicotinamide Riboside group not included in analysis due to abnormal lipids.

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 Mean Change in the TH17 Cell Cytokine IL-17 Secretion in Response to T-cell Differentiation, measured over Baseline and Day 28.

The primary endpoint is mean change in TH17-cell cytokine IL-17 secretion in response to T-cell differentiation, measured in pg/mL from baseline to Day 28. TH17 cells are a type of T cell, and IL-17 is the cytokine measured in this laboratory assay. The endpoint therefore captures a specific immune response under the stated differentiation conditions; it is not itself a direct measure of psoriasis severity, symptoms, or cardiovascular outcomes.

Change from baseline compares a participant’s measurement at follow-up with their starting measurement. Summarizing these changes by group allows the study to compare the average observed shift during the intervention period. In general, laboratory immune measures can be useful in an early or pilot study because they provide a defined biological outcome for evaluating a proposed effect on immune activity. That rationale does not establish that a change in this assay corresponds to a change in how participants feel or to a clinical benefit.

The registry reports the endpoint as a mean with standard deviation and gives the timeframe as baseline and Day 28. It does not provide additional assay-validation details, a threshold for a clinically important change, or a relationship between this outcome and later clinical outcomes. Interpretation should therefore remain tied to the measured IL-17 response and this short follow-up period.

7. Results Posted in the Registry

• Participants With Mild to Moderate Psoriasis Receiving Nicotinamide Riboside: mean -176.90 versus -7.20 on control; difference -169.70 (95% CI -285.80 to -53.60), standardized effect d = -1.10; z-test p = 0.004.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is measured on a numerical scale in pg/mL, and the registry summarizes it with group means and standard deviations. A mean is the arithmetic average of the observations in a group. A standard deviation describes the spread of individual measurements around that group’s mean. It is not a confidence interval and does not describe the precision of the mean by itself.

What does the mean difference represent?

The posted group means are -176.9 pg/mL for nicotinamide riboside and -7.2 pg/mL for placebo. The unadjusted mean difference is -169.7 pg/mL, expressed as the nicotinamide riboside group’s mean change relative to the placebo group’s mean change. A negative value indicates that the first group’s mean change is lower on the measured scale. This is a between-group contrast in average change, not a statement that every participant changed by that amount.

In general, a group comparison is more informative than looking at one group’s change alone because change can also occur in a comparison group. Randomization is intended to support a fair comparison of assigned groups, although the record does not provide enough detail to assess how well all baseline characteristics were balanced or whether the analysis followed the original assignment for every participant.

What does the t-test do?

The sponsor’s posted analysis is a two-sided t-test. In general, a t-test evaluates whether the observed difference in group means is compatible with a null value of no mean difference, while accounting for estimated variability and the number of observations. A two-sided test considers differences in either direction rather than only a prespecified direction. The registry reports p = 0.01 for this analysis. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or practical importance of a difference.

The recalculated result is an unadjusted comparison of the posted summary statistics. It reports a mean difference of -169.7 pg/mL, a 95% confidence interval from -285.8 to -53.6, and p = 0.004. The calculated comparison uses the posted means, standard deviations, and analyzed group sizes. It is not described in the registry as the sponsor’s analysis. The registry record does not report additional details that would explain the difference between the posted p-value and the recalculated p-value.

Why does variability matter?

The group standard deviations, 174.7 and 120.9, indicate that individual changes varied around their respective group means. In general, more variability makes a group mean difference harder to estimate precisely, because the same contrast is less clearly separated from the variation among participants. Small analyzed groups also leave less information for estimating the mean and its uncertainty. These points are especially relevant when interpreting a pilot study; they do not alter the values reported in the registry.

General statistical methods often rely on assumptions about the distribution of observations and the suitability of the analysis for the outcome. For a t-test, these considerations include the independence of observations and whether the mean comparison is adequately represented by the model. The registry identifies a two-sided t-test but does not report diagnostics, transformations, covariate adjustment, or other model details. No further assumptions about the actual analysis should be inferred from the reported test label alone.

What is the role of the confidence interval?

In general, a confidence interval presents a range of estimates compatible with the data and the method used to construct it. The recalculated 95% interval, from -285.8 to -53.6 pg/mL, describes uncertainty in the unadjusted mean difference. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval is for the group-average contrast, not for the spread of individual changes, and it does not guarantee that the true value lies within its endpoints.

The interval and p-value answer related but different questions. The interval emphasizes the range and precision of the estimated contrast; the p-value summarizes how unusual the data would be under a specified null model. Neither gives the probability that the result will replicate, and neither alone establishes clinical importance. The registry does not report a threshold for meaningful change on this assay.

What can and cannot be inferred from the posted analysis?

The posted primary analysis addresses the average change in one laboratory endpoint over the stated period. It does not report an analysis of symptom improvement, disease activity, cardiovascular events, or longer-term outcomes. The registry lists no posted secondary outcomes. Details of any multiplicity adjustment, analysis-population definition, handling of all missing measurements, or prespecified statistical analysis plan are not reported in the registry record.

Accordingly, the numerical result should be read as an estimate from the analyzed participants for this endpoint, alongside the sponsor’s reported test and the recalculated uncertainty. It should not be extended beyond the measured outcome, the recorded groups, or the baseline-to-Day 28 timeframe.

10. Confidence Intervals and Precision

The recalculated mean difference is -169.7 pg/mL, with a 95% confidence interval from -285.8 to -53.6. This interval expresses uncertainty about the between-group difference in average change, using the unadjusted recalculation. It is not a range containing 95% of individual participant changes, and it does not indicate that the effect for each participant was similar to the group estimate.

In general, a confidence interval combines the estimated contrast with its statistical uncertainty. A relatively wide interval permits a broader range of underlying mean differences than a narrow interval. The interval spans values of different magnitudes, so the estimate is not highly precise even though the interval does not include zero. Its endpoints should be considered along with the outcome’s units and the limited analyzed group sizes.

The group standard deviations were 174.7 pg/mL for nicotinamide riboside and 120.9 pg/mL for placebo. These describe observed variation, not precision of the estimated contrast. The registry reports the sponsor’s two-sided t-test p-value as 0.01, while the unadjusted recalculation gives p = 0.004. The record does not explain the difference. The sponsor’s result and the recalculated interval should therefore be identified as outputs from different reported analyses rather than combined as though they came from one fully specified model.

The confidence interval does not account for unreported design or analysis choices, and it cannot resolve limitations from missing measurements or the pilot setting. The registry record does not report a clinically important threshold for this assay, so the interval alone cannot indicate whether its values correspond to a meaningful clinical change.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustration is for future planning, not a description of the number analyzed in this trial. Its figures are participants per arm, not total event counts. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The registry record does not report the trial’s original sample-size assumptions or justification.

For planning for 100% of the observed effect, the illustration gives 13 participants per arm for 80% power and 18 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 23 participants per arm for 80% power and 31 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 52 participants per arm for 80% power and 69 participants per arm for 90% power.

In general, power is the probability that a planned study will identify a specified effect under the assumptions used for planning. The 80% and 90% columns describe two target probabilities for detecting the assumed effect, if the planning assumptions hold. The higher target generally requires more participants for the same effect. Smaller effects also require more participants to detect with the same target power, as reflected by the planning rows.

These figures are planning illustrations based on the observed effect, not observed power for this completed trial. The displayed curve should be read in the same planning context: its implications depend on the effect and assumptions used, and it does not show an outcome observed among participants.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -169.700; pooled standard deviation σ = 153.641.
2. n = 2 × (1.96 + 0.842)² × 153.641² / -169.700² = 12.9, rounded up to 13 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -169.7                      # observed difference in means
sigma <- 153.641206825456                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4271735)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 13 (80% power), 18 (90% power)
 75% of observed effect: n per arm = 23 (80% power), 31 (90% power)
 50% of observed effect: n per arm = 52 (80% power), 69 (90% power)
power.t.test: 13.9 
Simulated power at n = 13 per arm: 0.773 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a two-sided t-test, with p = 0.01 for the comparison of the nicotinamide riboside and placebo groups. This is the trial analysis recorded by the sponsor. The registry does not provide a sponsor-reported estimate or confidence interval for the mean difference in the analysis fields.

The unadjusted recalculation based on the posted group summaries gives a mean difference of -169.7 pg/mL, a 95% confidence interval from -285.8 to -53.6, and p = 0.004. It is a simple recalculation from those summaries, not a replacement for the sponsor’s analysis. The recalculation provides an estimate and interval useful for understanding the scale and uncertainty of the group contrast.

The two p-values are not identical. The registry record does not report why they differ, and the available information does not establish whether the difference reflects rounding, analysis details, or another cause. The record does not flag a discrepancy. The sponsor’s analysis and the recalculated result should therefore be presented with their respective sources and methods kept distinct, without treating one as an unexplained correction of the other.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcomes. It does not report a multiplicity adjustment or explain whether additional analyses were planned but not posted. When several outcomes or comparisons are tested, multiplicity can increase the chance of obtaining at least one apparently unusual result by chance. In general, statistical plans may address this through prespecified testing strategies or adjustment procedures. Whether any such approach was used in this trial is not reported in the registry record.

The record describes the primary analysis as a two-sided t-test, but does not report a detailed statistical analysis plan, covariate-adjusted analysis, or diagnostic checks. It also does not identify an intention-to-treat, per-protocol, or other formal analysis population. The reported group sizes for the primary outcome are 14 for nicotinamide riboside and 11 for placebo. The outcome description notes one placebo participant excluded because of insufficient T-cells and one nicotinamide riboside participant excluded because of abnormal lipids.

Those stated exclusions explain the two specifically identified omissions, but the registry does not give a full accounting of all missing observations or say how any other missing data were handled. It does not report whether participants with incomplete measurements were included in any alternative analysis, or whether sensitivity analyses were conducted. The participant flow between enrollment, allocation, follow-up, and analysis is not fully detailed in the outcome record.

These omissions matter because the composition of the analyzed groups and the approach to missing measurements can affect interpretation of a group comparison. The available record supports describing the posted analysis and the stated exclusions, but not assuming a particular analysis population, missing-data method, or multiplicity strategy.

15. 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.

Most frequent non-serious adverse event terms

The adverse-event record lists serious adverse events in zero participants in the nicotinamide riboside group, among 17 at risk, and zero participants in the placebo group, among 12 at risk. Deaths are listed as zero in both groups. For other, non-serious adverse events, the record lists one affected participant among 17 at risk in the nicotinamide riboside group and one among 12 at risk in the placebo group.

These figures are separate from the primary outcome analysis group sizes. The registry does not explain why the at-risk counts differ from the numbers included in the primary endpoint analysis, so the counts should be read as recorded for the adverse-event outcome rather than treated as interchangeable denominators.

In general, an adverse-event table records events observed and reported during the specified safety observation period. A zero count of serious events in this record means none were listed for the groups; it does not establish that an intervention has no risk. The record does not provide serious-event terms, and it does not include enough detail to characterize the one other event in either group. The safety counts should be interpreted in light of the pilot study’s size and the brief treatment period described in the registry.

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

The posted primary result is a comparison of mean change in a laboratory measure of immune activity from baseline to Day 28. The nicotinamide riboside group had a mean change of -176.9 pg/mL, and the placebo group had a mean change of -7.2 pg/mL. The unadjusted recalculation estimates a between-group mean difference of -169.7 pg/mL, with a 95% confidence interval from -285.8 to -53.6. The sponsor’s reported two-sided t-test has p = 0.01.

These findings describe the measured IL-17 response in the analyzed participants. They do not establish that the observed change caused a change in psoriasis severity, symptoms, or any cardiometabolic outcome. The primary endpoint is not a clinical outcome, and the registry does not report a threshold connecting changes in this assay to a clinically important benefit or harm.

The study is identified as a pilot and has a limited analyzed sample for the primary outcome. A pilot comparison can provide an estimate of a biological response and its variability, but the uncertainty remains important, and the result may not generalize beyond the population, assay, treatment duration, or procedures described in the record. The registry does not report longer-term results for this endpoint.

The record lists zero serious adverse events and zero deaths in each group, with one other adverse event listed in each group. Those observations are not enough to rule out risks that might be detected in a larger or longer study. Taken together, the posted data support a description of the measured group contrast and reported safety counts; they do not establish a clinical treatment effect or settle questions that the trial did not measure.

17. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation should separate the biological endpoint from a clinical outcome. The primary measure is a laboratory assay of TH17-cell IL-17 secretion, reported as change from baseline to Day 28. A difference in that measure can be scientifically informative while still leaving unanswered whether it corresponds to a change in psoriasis symptoms, disease activity, or later health outcomes.

It also shows the importance of reporting both an estimate and its uncertainty. The mean difference and confidence interval convey the direction, scale, and imprecision of the group comparison more clearly than a p-value alone. The standard deviations additionally show that individual changes varied within both groups. In a pilot study, those features can help shape expectations for later research without implying that the same estimate will recur.

The distinction between the sponsor’s reported test and a simple recalculation is another useful statistical lesson. The sponsor reports p = 0.01, while an unadjusted recalculation from the posted summaries gives p = 0.004 and a confidence interval. Keeping these results labeled by method avoids implying that they are identical outputs or that the reason for their difference is known.

Finally, the record makes visible several limits on interpretation: stated exclusions, absent details about missing-data handling and analysis populations, and no posted secondary outcomes. These details affect how confidently readers can assess robustness, but they do not erase what is reported. A careful reading identifies the specific biological result, its precision, the analysis that generated it, and the questions that remain unreported.

18. 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.

This was a pilot study with 29 participants enrolled, while the primary outcome analysis lists 14 participants in the nicotinamide riboside group and 11 in the placebo group. The outcome description identifies one exclusion in each group and gives the reasons as abnormal lipids and insufficient T-cells, respectively. The registry does not provide a complete participant flow or explain all differences between enrollment, safety denominators, and primary analysis counts.

The primary endpoint is a laboratory measure, and the registry does not report a clinically important threshold or evidence connecting the assay result to symptoms or longer-term outcomes. Follow-up for the primary endpoint is baseline to Day 28; the record does not provide longer-term results. Consequently, interpretation is limited to the stated measurement and period.

The record identifies a two-sided t-test and the sponsor’s p-value but does not report a detailed statistical analysis plan, analysis-population definition, missing-data method, multiplicity procedure, or sensitivity analyses. It also does not explain why the sponsor’s p-value differs from the unadjusted recalculation. These details limit assessment of the robustness of the result.

The safety record lists few events, but the study’s size and treatment period do not support broad conclusions about uncommon or later events. The registry’s original sample-size assumptions and justification are not reported. Although planning illustrations based on the observed effect are available, they are not the original design rationale and should not be used to infer the trial’s intended power.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Pilot Study to Evaluate the Effect of Nicotinamide Riboside on Immune Activation in Psoriasis — NCT04271735.
• Registry record last updated 2026-09-09; status last verified 2026-08.
• Results first posted 2023-12-27.
• 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.

22. Record Summary

The completed record describes a randomized, triple-masked, parallel-group pilot study of nicotinamide riboside versus placebo in people with mild to moderate psoriasis. The registry lists 29 participants enrolled. Treatment was taken twice daily for 28 days, and the primary endpoint was mean change in TH17-cell IL-17 secretion from baseline to Day 28.

The primary analysis lists 14 participants receiving nicotinamide riboside and 11 receiving placebo. Their mean changes were -176.9 pg/mL and -7.2 pg/mL, respectively. The sponsor reports a two-sided t-test with p = 0.01. An unadjusted recalculation gives a mean difference of -169.7 pg/mL, with a 95% confidence interval from -285.8 to -53.6 and p = 0.004.

The record lists no serious adverse events or deaths in either group, and one other adverse event in each group. It does not report secondary outcomes, the trial’s original sample-size justification, or several details of the analysis and missing-data procedures.