Host Modulatory Effects of β-glucan on Localized Aggressive Periodontitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Host Modulatory Effects of β-glucan on Localized Aggressive Periodontitis (NCT02402296), a randomized phase 4 study. The primary outcome is Assessment of Change in Clinical Attachment Level (CAL).

2. Clinical Question

The comparison concerns the treatment packages as described in the registry: both groups received scaling and root planing, while the capsules differed. The primary outcome is clinical attachment level, measured as the distance from the base of the pocket to the cemento-enamel junction using a Williams graduated probe. The registry lists the endpoint at day 0 and day 91 post therapy and reports the group results as mean percentage changes.

This is a question about the posted group-level results over the stated follow-up, not a guarantee that the observed contrast is causal or would recur in another study. The registry record does not report further details of eligibility criteria, recruitment setting, participant characteristics, adherence, or how the assessment was conducted while masking was in place. Those omissions limit how specifically the study population and conduct can be characterized.

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group, phase 4 trial, marked completed. Al-Azhar University is listed as sponsor. The recorded study start is 2013-01, and primary completion is recorded as 2014-06. Enrollment is listed as 30. The two groups each have 15 participants in the posted primary outcome results.

Both groups received scaling and root planing. The test group then received systemic β-1,3/1,6-D-glucan, described as a 100 mg capsule taken once per day for 40 days. The control group received empty capsules filled with carbohydrates for 40 days. The registry labels the comparator as placebo. The record does not describe the capsule appearance, matching procedures, allocation concealment, the method used to generate the random sequence, or which people were masked. The masking designation is triple, but the identities of the masked parties are not reported in the registry record.

The primary outcome was assessed at day 0 and day 91 post therapy. Pocket depth and gingival index are also listed as secondary measures with the same time points. Matrix metallo-proteinase MMP-1&9 is named as a secondary outcome, but its numerical results are not reported in the registry record. The trial is described as short term in its official title; the listed primary follow-up is day 91.

The registry record does not report the original sample-size justification, the prespecified statistical analysis plan, interim analyses, recruitment details, study sites, or the criteria used to define analysis populations. Those details should not be inferred from the observed group sizes or from the planning illustrations based on the posted results.

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

Analysis population for the primary outcome, as defined in the registry: A total of 30 localized aggressive periodontitis (LAP) participants were included in this study. Medical and dental histories were obtained and intraoral examinations were carried out at pre-screening visit. Patients were diagnosed to have LAP based on the clinical and radiographic findings measurements

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 Assessment of Change in Clinical Attachment Level (CAL), measured over Day 0 and day 91 post therapy.

The primary endpoint is assessment of change in clinical attachment level, reported as a percentage of change and summarized by the mean and standard deviation for each group. The registry defines clinical attachment level as the distance from the base of the pocket to the cemento-enamel junction, measured using a Williams graduated probe. Assessments are listed for day 0 and day 91 post therapy.

As general clinical measurement context, attachment level describes the position of periodontal attachment relative to a tooth landmark. Measuring change over time makes it possible to compare how this clinical measure shifted in the two randomized groups during the stated follow-up. The endpoint is therefore relevant to the trial’s stated question about change in periodontal status, but it is not itself a direct measure of every aspect of disease, symptoms, or longer-term outcomes.

The posted primary results are negative mean percentage changes in both groups. The test group’s mean is more negative than the control group’s mean, and the posted comparison expresses this contrast as a mean difference. The registry does not report the underlying individual measurements, the exact formula used to derive percentage change, or details of measurement reliability. Those omissions mean that the numerical summaries can be interpreted as posted but cannot be independently reconstructed from participant-level data.

7. Results Posted in the Registry

• Group II (Test Group): mean -37.48 versus -14.07 on control; difference -23.41 (95% CI -34.31 to -12.51), standardized effect d = -1.54; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Pocket Depth (PD)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group II (Test Group): mean -37.01 versus -21.84 on control; difference -15.17 (95% CI -25.84 to -4.50), standardized effect d = -1.02; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group II (Test Group) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Gingival Index (GI)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Group II (Test Group): mean -75.56 versus -0.87 on control; difference -74.69 (95% CI -87.79 to -61.59), standardized effect d = -4.08; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Group II (Test Group) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary measures include pocket depth, gingival index, and MMP-1&9. Numerical group summaries and comparisons are reported for pocket depth and gingival index. For both, the posted test-group mean change is more negative than the control-group mean change. This general pattern is directionally consistent with the primary clinical attachment level result, where the test-group mean is also more negative.

That consistency can be useful as descriptive context: the posted results do not show the primary contrast in isolation, but alongside related clinical measures. It does not establish that all measures capture the same aspect of periodontal status or that the secondary results independently verify the primary finding. The endpoints measure different quantities, and the registry does not report a joint analysis linking them.

The comparisons for the secondary outcomes are unadjusted. When multiple outcomes are examined, the chance of finding at least one nominally notable result can rise; general methods for multiplicity control address that issue by accounting for a family of comparisons. The registry record does not report a prespecified multiplicity strategy or adjusted results. Accordingly, the secondary comparisons carry less inferential weight than a single, prespecified primary endpoint, and their unadjusted p-values should not be treated as confirmatory evidence.

MMP-1&9 is listed among the secondary outcomes, but numerical results for it are not reported in the registry record. The record also does not give a complete account of which outcome analyses were prespecified or how all listed outcomes were handled. This makes it difficult to assess selective reporting or to interpret the full set of planned comparisons. The secondary pattern is therefore best read as supportive description, with uncertainty about the analysis and reporting context.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Pocket Depth (PD)
• Gingival Index (GI)
• Matrix Metallo-proteinase (MMP-1&9)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: clinical attachment level is summarized as percentage change, with a mean and standard deviation for each group. For a continuous outcome, the mean describes the group’s average reported change. The standard deviation describes the spread of participant values around that group average; it is not the uncertainty of the mean itself. General statistical interpretation should keep those two ideas separate.

What does the mean difference represent?

The posted primary mean difference is -23.41 for the test group relative to the control group. This is the contrast between the groups’ mean percentage changes, expressed in the outcome’s reported units. The sign depends on the order of the comparison: the result is presented as test relative to control. Because the group means are negative and the test-group mean is more negative, the negative contrast indicates a more negative mean change in the test group. It should not be recast as an absolute change in the measured distance, since the registry reports percentage change.

A group contrast is useful because both arms were followed over the same stated period and had the same listed scaling and root planing procedure. However, the registry does not state whether the primary comparison was adjusted for baseline values or other variables. The posted group summaries and unadjusted comparison should therefore be read as the information available in the record, not as evidence of an unreported adjusted model.

How should the confidence interval be read?

A confidence interval describes uncertainty around an estimated effect under the statistical procedure used. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The primary interval extends from -34.31 to -12.51. It is entirely below zero, so the range of values compatible with this calculation is in the direction of a more negative mean change in the test group. The interval does not capture possible bias from trial conduct, measurement, missing data, or selective reporting.

The interval is not a range containing every individual participant’s response. It is also not a guarantee that the true effect lies within its endpoints. General interpretation of a confidence interval relies on the assumptions of the method used; details of the trial’s own statistical procedure are not reported in the registry record.

What does the p-value add?

The primary comparison has an unadjusted p-value of <0.001. In general, a p-value describes how incompatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null model is true, nor a measure of the size or clinical importance of the effect. Because it is unadjusted, it does not account for the possibility of multiple outcomes or comparisons. The registry does not report a complete analysis plan or whether the displayed comparison matches the trial’s prespecified analysis.

The registry record lists no reported analyses, although it contains outcome summaries and comparisons. This distinction matters: numerical summaries and calculated contrasts can be described, but the record does not document the modeling choices or inferential procedures as a formal analysis report. The comparison should therefore be interpreted as an unadjusted contrast of the posted summaries.

What do standard deviations and standardized effects contribute?

The primary group standard deviations are 12.29 in the control group and 17.69 in the test group. They describe variability in the reported change values within each arm. The comparison information also gives a pooled standard deviation of 15.23 and a standardized effect, d, of -1.537. In general, a standardized effect expresses a contrast in standard-deviation units rather than in the original outcome units. It can help compare effect scales across measures, but it does not replace the clinical interpretation of the outcome and is sensitive to variability in a small study.

The registry does not report whether any distributional checks were made, whether influential observations were assessed, or whether an alternative analysis was considered. General methods for continuous outcomes can depend on the distribution of the data and on the validity of assumptions about sampling and variability. Without participant-level data and analysis details, those assumptions cannot be evaluated from the registry summaries alone.

What remains unknown about the analysis?

The record does not report the original sample-size justification, analysis population definitions, missing-data procedures, imputation methods, covariate adjustments, or methods for handling multiple endpoints. It also does not report interim analyses. These are not details that can be reconstructed from the p-value or confidence interval. They are important because analytical choices can affect uncertainty and interpretation, especially when several outcomes are assessed.

The sample-size illustrations use the observed effect as a planning reference and state their own assumptions. They are separate from the trial’s original design, whose assumptions are not reported in the registry record. The illustrations should not be taken as proof that the trial was planned around those assumptions. More generally, a planning exercise based on an observed effect inherits uncertainty from the study estimate and can yield optimistic target sizes when that estimate is unusually large.

11. Confidence Intervals and Precision

The primary mean difference is -23.41, and its 95% confidence interval runs from -34.31 to -12.51. The interval is entirely on the negative side, indicating that the estimated contrast is not centered near zero under the reported calculation. Its endpoints also show that the estimate has uncertainty: the data are compatible with a range of negative mean differences rather than one exact value. The interval is expressed in the reported percentage-change scale.

In general, confidence intervals are useful because they convey both direction and precision, whereas a p-value alone does not show the range of effect estimates consistent with the data. A confidence interval is not a description of individual outcomes, and its width does not account for possible biases in selection, measurement, analysis, or reporting. The registry record does not provide enough detail to assess those sources of uncertainty.

The primary group sizes are 15 in each arm. Such group sizes make the precision of estimates especially important to consider, but the interval should be interpreted on its own terms rather than translated into certainty about future studies. The record does not report a clinical-importance threshold, so the statistical interval cannot establish whether every value it contains would be clinically meaningful.

For the secondary measures with numerical comparisons, the posted intervals also lie below zero. Those results should be considered alongside the primary endpoint and the lack of a reported multiplicity plan. A nominal interval does not automatically retain its usual coverage interpretation across a family of outcomes when multiple testing is not accounted for. The registry does not provide intervals for MMP-1&9.

12. 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 illustrations are planning calculations, not a report of the trial’s original design rationale. The figures are participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The stated 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 set as the stated fraction of the observed effect. The original design assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the selected effect under those assumptions, if that effect were the true one and the assumptions held. The 90% column represents a higher target probability of detection, which generally requires more participants per arm than the corresponding 80% target. These are planning illustrations, not observed power.

Rows for 100%, 75%, and 50% of the observed effect ask what the planning requirement would be if the effect of interest were the full observed estimate or a smaller fraction of it. Smaller effects generally require more participants to distinguish them from random variation at the same significance and power targets. This relationship is especially important when the observed effect comes from a small study, because it may be imprecise and may not be a stable estimate for future planning.

The curve should be read as another display of the relationship between the assumed effect size and the resulting participant requirement under the stated assumptions. It does not show what happened to participants in the completed trial, and it does not establish that a future study will achieve the calculated power. The illustrations should not be confused with observed power or with the unreported sample-size justification for this trial.

13. 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 = -23.410; pooled standard deviation σ = 15.231.
2. n = 2 × (1.96 + 0.842)² × 15.231² / -23.410² = 6.6, rounded up to 7 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 <- -23.41                      # observed difference in means
sigma <- 15.2312212248395                     # 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(2402296)
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 = 7 (80% power), 9 (90% power)
 75% of observed effect: n per arm = 12 (80% power), 16 (90% power)
 50% of observed effect: n per arm = 27 (80% power), 36 (90% power)
power.t.test: 7.7 
Simulated power at n = 7 per arm: 0.753 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, but it does not report a plan for controlling multiplicity. When several endpoints are tested, each comparison can add opportunities for a chance finding. General statistical approaches may define a family of tests and adjust inference or designate a hierarchy of outcomes. The record does not say whether either approach was used. The posted secondary p-values are unadjusted, so they should not be interpreted as if a family-wise error rate had been controlled.

The registry record does not report the trial’s full statistical analysis plan, a prespecified hierarchy among secondary outcomes, or whether outcomes were selected for reporting after results were known. The absence of these details does not prove selective reporting; it means that the record does not allow readers to evaluate it. The stated primary endpoint is identifiable, but its analysis population and statistical procedure are not documented in the posted record.

Missing-data handling is also not reported in the registry record. There is no description of withdrawals, incomplete outcome assessments, reasons for missingness, imputation, or sensitivity analyses. The posted outcome groups each have 15 participants, but that alone does not establish how many randomized participants were assessed at each time point or whether the listed groups represent an intention-to-treat population.

The record does not define intention-to-treat, per-protocol, or safety populations, and it does not report how protocol deviations were handled. It also does not report baseline adjustment, interim analyses, or a prespecified approach for repeated measurements. These are unknown features of the analysis, not evidence that a particular method was or was not used. The limits matter because analysis choices can influence estimated effects and uncertainty.

15. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports zero serious adverse events affecting participants in the control group and zero in the test group. Each group lists 15 participants at risk for serious events. It also reports zero other, non-serious adverse events affecting participants in either group, with 15 at risk in each group. No serious adverse-event terms are listed.

These figures describe the adverse-event counts entered in the registry; they do not establish that no symptoms or harms occurred in any broader sense. The registry does not report the definitions used for serious and other events, the surveillance and reporting procedures, event severity beyond those categories, or exposure-adjusted rates. Death counts are not reported in the registry record. The figures should therefore be read as the posted registry counts, not as a complete characterization of safety or as a basis for treatment advice.

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

The posted primary results show a more negative mean percentage change in clinical attachment level in the β-glucan group than in the placebo group over the stated assessment period. The estimated test-versus-control mean difference is -23.41, with a 95% confidence interval from -34.31 to -12.51 and an unadjusted p-value of <0.001. These statistics describe the observed group summaries and the uncertainty calculated around their contrast.

They do not prove that the capsule regimen caused the entire difference, that the same contrast would occur in other populations, or that the difference meets a clinically important threshold. The registry does not report such a threshold. The trial compared two treatment packages that both included scaling and root planing, and the record does not provide enough information to separate treatment effects from other influences or to assess all aspects of trial conduct.

The results also do not establish longer-term effects. The listed primary assessment is at day 91 post therapy, and longer follow-up results are not reported in the registry record. The record does not provide individual-level data, adherence information, or a missing-data analysis, so readers cannot assess the distribution of responses or the sensitivity of the result to incomplete measurements.

Finally, a small p-value is not a measure of clinical importance, and the absence of reported adverse events is not proof that adverse effects cannot occur. The posted data are informative about the recorded outcomes and follow-up in this trial, while leaving important questions about generalizability, durability, and analysis methods unanswered.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through its endpoint, contrast, and uncertainty rather than through a p-value alone. The primary result is reported as a mean percentage change, with a group-level mean difference and confidence interval. Reading the interval alongside the estimate preserves information about both direction and precision.

The study also makes a useful distinction between the treatment comparison and the shared care in both groups. Since both arms received scaling and root planing, the trial’s contrast concerns the added capsule regimen in that context. Treating the result as a comparison of β-glucan with no treatment would misstate the design.

Another statistical lesson is the difference between observed results and planning calculations. The sample-size illustrations use fractions of the observed effect and explicit assumptions; they do not reveal the rationale used when the completed trial was designed. Planning around an observed estimate can be uncertain, so assumptions and effect sizes need to be considered separately from the trial’s actual enrollment.

The record also highlights the importance of transparent analysis reporting. Multiplicity, missing-data procedures, analysis populations, and prespecified methods are not reported, while the secondary comparisons are unadjusted. These omissions do not invalidate the posted summaries, but they limit how strongly the secondary results can be interpreted and how fully the primary inference can be audited. Statistical reading therefore includes identifying both what the registry supports and what it leaves unknown.

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.

The posted groups are small, with 15 participants in each arm for the primary outcome. Estimates from groups of this size can be sensitive to individual observations, while the registry provides no participant-level data or distribution plots from which to assess that sensitivity. Standard deviations are reported, but no additional distributional summaries are available in the registry record.

The primary assessment is at day 91 post therapy. This provides a short-term view and does not establish whether the observed pattern persists beyond that time. Longer-term outcomes are not reported in the registry record. The registry also does not report adherence to the 40-day capsule course, withdrawals, or the completeness of outcome measurement.

Important methodological details are absent: the random-sequence method, allocation concealment, identity of masked parties, original sample-size rationale, statistical analysis plan, analysis population, missing-data method, and multiplicity strategy are not reported. The record does not report baseline characteristics in a way that permits assessment of group comparability, nor does it provide numerical results for MMP-1&9. These gaps restrict evaluation of internal validity and the breadth of the evidence.

The study addresses people described as having localized aggressive periodontitis. The registry record does not report enough eligibility or setting information to determine how closely participants resemble populations in other clinical contexts. The result should therefore remain tied to the specific groups, interventions, endpoint, and follow-up recorded, rather than assumed to apply more broadly.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Host Modulatory Effects of β-glucan on Localized Aggressive Periodontitis — NCT02402296.
• Registry record last updated 2015-06-09; status last verified 2015-05.
• Results first posted 2015-06-09.
• 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 registry describes a completed, randomized, triple-masked, parallel-group, phase 4 trial sponsored by Al-Azhar University. It compared scaling and root planing plus β-1,3/1,6-D-glucan with scaling and root planing plus placebo in participants with localized aggressive periodontitis. Enrollment is listed as 30.

The primary endpoint was percentage change in clinical attachment level between day 0 and day 91 post therapy. The posted test-group mean was more negative than the control-group mean, and the unadjusted comparison had a 95% confidence interval entirely below zero. Pocket depth and gingival index show a directionally similar secondary pattern, while numerical results for MMP-1&9 are not reported in the registry record.

The record does not report the original design assumptions, full analysis plan, missing-data procedures, analysis populations, or a multiplicity strategy. The posted results describe the recorded short-term group summaries, with those reporting limitations in mind.