Effects of rhLactoferrin on Chronic Inflammation in the Elderly: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of rhLactoferrin on Chronic Inflammation in the Elderly (NCT02968992), a randomized phase 2 study. The primary outcome is The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6).

2. Clinical Question

This is a question about a measured biomarker over the study period, not a direct test of whether participants experienced a meaningful improvement in mobility or cognition. The registry’s broader rationale connects chronic inflammation with physical and cognitive function, but the posted primary comparison concerns serum IL-6. Its result should therefore be interpreted on that endpoint’s scale and alongside the uncertainty around the estimated group difference.

3. Trial Design

The registry identifies NCT02968992 as a completed phase 2 randomized, parallel-group trial with triple masking. The listed sponsor is Johns Hopkins University. The study began on 2017-08-14, and its primary completion date is 2019-02-25. Enrollment is listed as 36. The registry record does not report the trial’s original sample-size justification or the precise people or roles covered by triple masking.

The active arm received rhLactoferrin, while the comparator arm received matching placebo capsules. The arm descriptions specify six 250 mg rhLactoferrin capsules twice a day for six months and six placebo capsules twice a day. The registry’s study summary describes daily dosing over a 6 month period and collection of blood samples alongside physical and cognitive testing.

The primary outcome is the effect of rhLactoferrin on serum IL-6, expressed as percent change from baseline and assessed at baseline and 6 months. The registry also lists six secondary outcomes: cognitive tests, mobility tests, grip strength, and a patient-diary count of side effects. It lists 8 outcome measures in total. The posted primary-outcome arm summaries are based on 18 participants in the rhLactoferrin group and 17 in the placebo group. These outcome counts are not the same as the enrollment figure; the registry record does not explain the difference.

The record labels the study completed, but the label alone does not describe adherence, follow-up completeness, or how participants were included in each analysis. Those details are not reported in the registry record. The posted comparison is therefore best read as a summary of the outcome data available in the registry, rather than as a complete account of trial conduct or analysis.

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

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 The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6), measured over Baseline and 6 months.

The primary endpoint is the percent change in serum IL-6 from baseline, assessed at 6 months. IL-6 is a blood biomarker, and the registry describes it as a measure of chronic inflammation. A continuous endpoint retains the magnitude of measured values rather than reducing them to categories such as improved or not improved. The reported arm summaries are means with standard deviations.

The registry’s rationale is that chronic inflammation may be connected with physical and cognitive function. Measuring a biomarker can therefore address whether the intervention is associated with a change in an inflammation-related laboratory measure. It does not, by itself, establish a corresponding change in mobility, memory, strength, or how participants feel. Those domains appear among the secondary outcomes, but the primary result is IL-6.

The endpoint description refers to percent change in serum IL-6 levels from baseline, while the measurement timeframe is baseline and 6 months. The registry does not provide the calculation details for the percentage change or additional information about laboratory procedures. The outcome is listed as a mean with standard deviation, so the treatment comparison concerns average values and their variability, not an individual participant’s response.

In the posted results, the mean percent change is -0.64 for rhLactoferrin and 0.932 for placebo. The estimated mean difference is -1.572, defined in the posted comparison by the rhLactoferrin mean relative to the placebo mean. That estimate describes the direction and size of the average difference on this endpoint’s scale; its confidence interval describes the statistical uncertainty around it.

7. Results Posted in the Registry

• rhLactoferrin: mean -0.64 versus 0.93 on control; difference -1.57 (95% CI -2.11 to -1.03), standardized effect d = -1.88; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: the registry reports a mean percent change in serum IL-6 for each arm, together with a standard deviation. A mean describes the average observed value in a group. A standard deviation describes how dispersed individual values are around that average. It is not the uncertainty in the mean itself; uncertainty in a comparison also depends on the group sizes and the statistical model used.

What does the mean difference represent?

The posted contrast is a mean difference, with the rhLactoferrin arm compared against placebo. It is reported as -1.572. The negative sign indicates that the rhLactoferrin group’s average percent change is lower than the placebo group’s average percent change on the registry’s outcome scale. This contrast retains the scale of the endpoint. It is not a standardized effect and should not be interpreted as a percentage reduction in a clinical outcome.

The arm means are -0.64 for rhLactoferrin and 0.932 for placebo. The registry also reports standard deviations of 1.137 and 0.265, respectively. The spread differs between the arms, and this is one reason not to infer the uncertainty of the comparison from the group means alone. The posted confidence interval and p-value are the comparison statistics to use for the registry’s reported analysis.

What does a confidence interval tell the reader?

A confidence interval is an uncertainty summary around an estimate. In general, it describes the range of values that are compatible with the observed data and the interval procedure, under its assumptions. It is not a guarantee that the true value lies in that specific interval, nor does it describe the range of individual participant outcomes. The reported interval for the mean difference is -2.112 to -1.032.

The interval is centered around the estimated difference in the sense relevant to the reported analysis, and its limits show that the estimate has uncertainty. Because both limits are negative, the interval does not include a zero mean difference. This is a statement about the comparison’s statistical scale, not a conclusion about practical importance. The registry does not report a threshold for a clinically meaningful difference.

How should the p-value be read?

The posted p-value is unadjusted and reported as p < 0.001. In general, a p-value assesses how unusual results at least as incompatible with a null hypothesis would be if that null hypothesis and the test assumptions held. It is not the probability that the result is due to chance, and it does not give the size or importance of the effect. The unadjusted label matters because the record also lists secondary outcomes, while adjustment for multiple testing is not reported.

Why can variability matter?

When group variability differs, a pooled standard deviation may not describe each group equally well. In general, unequal dispersion can affect standard errors and the behavior of methods that assume similar variance across groups. The posted comparison includes a pooled standard deviation of 0.837 and reports that it was not approximated. The registry does not describe the comparison’s full modeling details, diagnostics, or whether variance assumptions were evaluated. The pooled value is a statistical summary and does not erase the differing arm-level standard deviations.

Over-dispersion is a general issue when data vary more than a model expects. If a model assumes less variability than the data contain, its uncertainty estimates can be too small and inferential results can be overstated. That concept is relevant to statistical reasoning, but the registry does not report that over-dispersion was identified or that a particular model was used to address it. It would be inappropriate to infer such an analysis from the posted summaries.

What does randomization contribute?

Random allocation is intended, in general, to make comparison groups less systematically different at the start of a trial than groups formed by participant choice or clinical selection. It supports an interpretation of the contrast as a comparison between assigned groups, but it does not guarantee balance in a modest trial or resolve missing-data and adherence questions. The registry labels allocation randomized; it does not report the sequence-generation or allocation-concealment procedures.

The trial is listed as triple masked. Masking can, in general, reduce the influence of expectations on participant reports, clinical decisions, or outcome assessment, depending on which roles are masked. The registry does not identify the masked roles or describe how masking was maintained. The trial is also listed as parallel, meaning the registry describes separate intervention arms rather than a crossover comparison; further design details are not reported.

What can be inferred from the posted analysis?

The registry reports one primary comparison with arm means, standard deviations, a mean difference, confidence limits, and an unadjusted p-value. The record does not provide an analysis protocol, model specification, covariate-adjustment details, or analysis-population definition. The interpretation should remain tied to the reported summary rather than assuming methods that are not documented. The six secondary outcomes concern cognition, mobility, grip strength, and side effects, but the registry’s primary result does not establish results for those outcomes.

These statistical concepts explain how to read the reported estimate and uncertainty; they do not establish whether the underlying assumptions were met in this trial. Further details about missingness, outliers, distributional checks, multiplicity, and outcome calculation are not reported in the registry record.

10. Confidence Intervals and Precision

The reported mean difference in percent change in IL-6 is -1.572. Its 95% confidence interval extends from -2.112 to -1.032. The interval provides a precision summary for the estimated comparison: it shows that the estimate is not exact and gives a range of values compatible with the data under the interval procedure and its assumptions. It is not a range containing 95% of participant values.

Both limits are below zero, so the reported interval does not include a zero mean difference. That conveys evidence of a difference on the statistical scale used for the comparison. The interval’s limits also make clear that the precise magnitude remains uncertain. The registry does not report a threshold for an important or meaningful change in IL-6, so the interval cannot by itself determine practical or clinical importance.

The arm-level standard deviations are 1.137 for rhLactoferrin and 0.265 for placebo. The reported group sizes for the primary outcome are 18 and 17, respectively. Precision depends on variability as well as group size and the analysis method. The registry does not report enough methodological detail to independently assess all assumptions behind the interval.

The unadjusted p-value is p < 0.001. It addresses a null comparison under the test assumptions and is not a substitute for the confidence interval. Neither statistic resolves unreported questions about missing data, analysis populations, or multiplicity. Together, the estimate and interval describe the posted primary comparison; they do not establish precision for the secondary outcomes or for other populations and settings.

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 figures are planning illustrations based on fractions of the observed mean difference, not counts of people enrolled in the trial. They are reported as participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. These assumptions describe the illustration, not the trial’s original design plan; the original design assumptions and sample-size justification are not reported in the registry record.

For planning for 100% of the observed effect, the illustration gives 5 participants per arm for 80% power and 6 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 8 participants per arm for 80% power and 11 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 18 participants per arm for 80% power and 24 participants per arm for 90% power.

The 80% power column describes the illustrated number of participants per arm for a design with an 80% chance of detecting the chosen effect under the listed assumptions, if that effect and assumptions hold. The 90% column describes the corresponding planning target for a 90% chance. These are design concepts, not guarantees for a future study. Smaller effects need more participants to detect under the same assumptions, as reflected by the larger figures for the smaller fractions.

This is not observed power. The figures are recalculated planning illustrations using the posted effect and are not evidence that the completed trial had a particular probability of detecting its result. The registry does not report the assumptions used for its original enrollment target.

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 = -1.572; pooled standard deviation σ = 0.837.
2. n = 2 × (1.96 + 0.842)² × 0.837² / -1.572² = 4.4, rounded up to 5 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 <- -1.572                      # observed difference in means
sigma <- 0.836672214155217                     # 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(2968992)
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 = 5 (80% power), 6 (90% power)
 75% of observed effect: n per arm = 8 (80% power), 11 (90% power)
 50% of observed effect: n per arm = 18 (80% power), 24 (90% power)
power.t.test: 5.6 
Simulated power at n = 5 per arm: 0.742 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the primary IL-6 endpoint and six secondary outcomes. The secondary outcomes include cognitive performance, physical mobility, grip strength, and a patient-diary count of side effects. When several outcomes are tested, the chance of at least one apparently notable finding can increase if each is evaluated separately. In general, multiplicity procedures can control that risk, but they may also change the interpretation or precision of individual tests.

The posted IL-6 p-value is explicitly unadjusted. The registry record does not report a multiplicity plan, whether adjustment was applied, or how the primary and secondary outcomes were prioritized for formal inference. The posted primary result should therefore be read as an unadjusted comparison, without assuming a family-wise or other correction. No result for the listed secondary outcomes is included in the registry summaries.

The record lists 0 analyses, despite posting arm-level primary outcome summaries and a comparison. It does not explain this listing. The specific statistical analysis plan, including model form and covariate adjustment, is not reported in the registry record. The record also does not define the analysis population, such as whether the analysis followed assignment regardless of treatment received.

Missing-data handling is not reported. The registry does not say whether outcome measurements were missing, how any missing values were treated, or whether sensitivity analyses were conducted. The primary-outcome group counts are 18 for rhLactoferrin and 17 for placebo, while enrollment is listed as 36; the record does not explain the difference. These registry entries do not identify the reason for the count discrepancy or establish how missingness may have affected the result.

More detail on outcome availability, participant flow, adherence, protocol deviations, and the statistical analysis plan would help readers assess the analysis population and robustness of the estimate. Without that information, interpretation should stay with the posted comparison and avoid assumptions about unreported analyses.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (5.6%).

The registry lists serious adverse events for 0 of 18 participants at risk in the rhLactoferrin group and 1 of 18 participants at risk in the placebo group. It lists 0 deaths in each group. Hospitalization is the top serious-event term, reported as 5.6%. The registry record does not provide further detail about the event or its relationship to study treatment.

These are counts in the posted safety record, not a comparative statistical analysis. They do not establish whether an event was caused by treatment, and no uncertainty interval or hypothesis test for the serious-event comparison is reported. A small number of events also gives limited information about uncommon harms. The registry’s listed figures should not be treated as a complete account of all possible safety outcomes.

The record separately lists other adverse events affecting 13 of 18 participants in the rhLactoferrin group and 15 of 18 in the placebo group. The registry does not provide further details in these summary figures about event types, severity, timing, or attribution. Safety interpretation is therefore limited to the counts and event term recorded, rather than a conclusion about comparative tolerability.

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

The posted primary result is a mean difference of -1.572 in percent change in serum IL-6, comparing rhLactoferrin with placebo. The 95% confidence interval runs from -2.112 to -1.032, and the unadjusted p-value is p < 0.001. The result indicates a difference in average change on the primary biomarker scale in the posted outcome groups. It is a statistical finding for this endpoint, not a direct measure of function or quality of life.

The record’s rationale concerns chronic inflammation and its possible relationship to mobility and memory. It also lists secondary outcomes for cognitive tests, walking tests, grip strength, and side effects. The posted primary comparison does not establish effects on those outcomes. The registry record does not report results for the six listed secondary outcomes in the summaries, so their direction and precision cannot be inferred from the IL-6 result.

A change in a biomarker is not automatically a meaningful benefit to participants. The registry does not specify a clinically meaningful threshold for IL-6, nor does it connect the observed difference to a functional threshold. The point estimate and confidence interval describe statistical magnitude and uncertainty, but do not settle the practical importance of the change.

The trial was randomized and is listed as triple masked, features that are relevant to how a comparison is designed. However, the registry does not report important details such as the masked roles, analysis population, handling of missing data, or multiplicity plan. These omissions limit what can be concluded about robustness and generalizability from the record alone.

The result should not be taken as proof that rhLactoferrin changes all aspects of chronic inflammation, improves mobility or memory, or has a particular safety profile. It describes the posted IL-6 comparison in this completed phase 2 trial. Broader conclusions would require evidence addressing those separate outcomes and the limitations in the registry’s reporting.

16. Why This Trial Matters Statistically

This trial illustrates why a statistical result should be read at the level of the endpoint actually measured. The primary outcome is percent change in a blood biomarker, and its mean difference is reported with a confidence interval. The interval adds information about uncertainty that a point estimate or p-value alone cannot convey. It also helps distinguish evidence for a statistical difference from evidence about whether that difference matters to participants.

The contrast has a clear direction on the reported scale: average percent change in IL-6 was lower in the rhLactoferrin arm than in the placebo arm. But the trial’s motivation also invokes mobility and memory, which are different constructs from serum IL-6. Keeping the biomarker result separate from functional outcomes prevents a statistical association in one measure from being overstated as evidence about another.

The record also demonstrates the importance of analysis transparency. It provides arm summaries and an unadjusted comparison, while not reporting multiplicity handling, missing-data methods, the analysis population, or the full statistical plan. Those details shape how confidently readers can connect a posted estimate to the randomized trial and how they should interpret a result among several outcomes.

Finally, the planning illustrations show that sample-size targets depend on the effect chosen for detection and on explicit assumptions. Smaller effects require larger planning figures under the same assumptions. Such calculations help frame design choices, but they are not observed power and do not recover the original trial’s design rationale. This distinction matters when translating a completed trial’s observed result into questions for future research.

17. 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 reports enrollment of 36, while the primary outcome summaries include 18 participants in the rhLactoferrin arm and 17 in the placebo arm. It does not explain the difference, describe participant flow, or state whether the outcome counts reflect missing measurements, exclusions, or another analysis choice. The reason should not be inferred from the summaries.

The registry record does not report the original sample-size calculation, the allocation procedure, the roles covered by triple masking, or a detailed statistical analysis plan. It also does not state how missing data, protocol deviations, treatment adherence, or covariates were handled. These gaps limit assessment of potential bias and of how reproducible the posted analysis would be.

Although the primary comparison is reported with a confidence interval and an unadjusted p-value, the registry does not report whether or how multiplicity was considered alongside the listed secondary outcomes. The record lists six secondary outcomes but does not include their results in the posted outcome summaries. The primary biomarker finding therefore cannot be used to infer results for those measures.

The primary endpoint is an inflammation-related biomarker, and the registry does not provide a threshold for meaningful change or a link between the measured difference and a functional outcome. The adverse-event summary gives counts and a serious-event term, but lacks detail on timing, severity beyond the serious classification, attribution, and event descriptions. These reporting limitations constrain conclusions about clinical relevance and safety.

The trial is listed as phase 2 and completed. The registry record alone does not establish how results apply beyond the studied population or duration, and does not report follow-up beyond the stated outcome timeframe. These limitations are specific to the information recorded and should be kept distinct from the statistical estimate itself.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effects of rhLactoferrin on Chronic Inflammation in the Elderly — NCT02968992.
• Registry record last updated 2023-10-03; status last verified 2023-09.
• Results first posted 2020-03-26.
• 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.

21. Record Summary

NCT02968992 is a completed phase 2 randomized, parallel-group, triple-masked trial sponsored by Johns Hopkins University. It enrolled 36 participants and compared rhLactoferrin with matching placebo. The registry describes six 250 mg rhLactoferrin capsules twice a day for six months.

The primary outcome was percent change in serum IL-6 from baseline to 6 months. The posted mean difference was -1.572, with a 95% confidence interval from -2.112 to -1.032 and an unadjusted p < 0.001. The outcome groups included 18 participants assigned to rhLactoferrin and 17 assigned to placebo.

The record lists secondary outcomes concerning cognition, mobility, grip strength, and side effects. It also records serious adverse events and deaths by group. Details about the analysis population, missing data, multiplicity, and the original sample-size justification are not reported in the registry record. The primary result should be interpreted as a comparison of the posted IL-6 outcome, not as a result for the broader functional questions.