Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis (NCT04118010), a randomized phase 4 study. The primary outcome is Shannon Index.

2. Clinical Question

The registry describes a study of whether vitamin D3, inulin, or their combination could affect gastrointestinal dysbiosis and intestinal functions in people with cystic fibrosis. Its stated aim was to assess the possible additive or synergistic effects of vitamin D plus inulin. The record identifies cystic fibrosis and dysbiosis as conditions of interest, but its population field does not specify further participant characteristics.

3. Trial Design

This was a randomized, double-masked, parallel-group, phase 4 trial sponsored by Emory University. The registry lists enrollment of 40 and a completed status. The recorded start date is 2020-03-13, and the primary completion date is 2022-12-31. Completion describes the trial’s status in the registry; it does not establish that results or analyses were posted.

The treatment groups combined active or placebo vitamin D3 with active or placebo inulin. The active vitamin D3 regimen was 50,000 IU/week. Active inulin was chicory-derived and given at 12 g/day. The prebiotic placebo was corn-derived maltodextrin at 12 g/day. Each described regimen lasted 12 weeks. The record does not give the method used to generate the random sequence, how assignments were concealed, or which people were masked.

The parallel design means participants were assigned to a treatment combination rather than described as crossing between combinations. Although the combinations include both components and their placebos, the registry record does not specify whether the planned analysis treated the study as a factorial design or estimated interaction effects. It also does not report the allocation ratio, the number assigned to each treatment group, or the number included in the primary outcome analysis.

The study’s stated focus was intestinal health in cystic fibrosis, while the primary outcome description specifies sputum samples collected using a sputum kit. That distinction matters when interpreting what the primary measurement represents: it is a microbial diversity measure from sputum, whereas gastrointestinal microbiota outcomes are listed separately as secondary outcomes. Eligibility details, recruitment procedures, and the protocol’s statistical analysis plan 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

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.

Population: Patients analyzed include participants that completed the trial.

6. Primary Endpoint

The registry lists the primary outcome as Shannon Index, measured over Baseline, 12 weeks post-intervention.

The primary endpoint was the Shannon Index, a continuous measure of microbial diversity. The registry describes it as accounting for both abundance—the number of species present—and evenness—how close the numbers for each species are. The recorded measurement was based on sputum microbiota analysis, with sputum samples collected using a sputum kit. The timeframe was baseline and 12 weeks post-intervention.

As described in the registry, the index is calculated as H = −∑ pi ln(pi). A value of zero indicates a community with only one species; higher values indicate greater species diversity. The measure is useful because it combines information about how many species are represented and how evenly their abundances are distributed. It does not, by itself, identify which species are present, describe their functions, or establish a clinical consequence.

The outcome was described using a mean and standard deviation. Those summaries can convey the group’s average index and the spread of individual measurements, but an average alone does not show the range of observations or the precision of a treatment comparison. The registry record does not report the endpoint values, changes, or a comparison between treatment groups. The gastrointestinal microbiota outcomes were listed separately as secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-masked, parallel trial. Randomization is intended, in general, to reduce systematic differences between assigned groups by allocating treatment independently of participant characteristics. It does not guarantee that the groups will be identical, especially in a study with limited enrollment. The record does not explain the randomization sequence, allocation concealment, masking procedures, or whether masking was assessed.

What do the reported mean and standard deviation describe?

The primary measure is continuous, and the registry specifies a mean and standard deviation. The mean locates the center of a group’s observed index values. The standard deviation describes how dispersed those values are around the mean. These summaries answer different questions: a mean describes the average level, while a standard deviation describes variability between observations. Neither alone estimates a treatment contrast or its uncertainty.

For a comparison, an analysis might compare outcome levels at follow-up, compare changes from baseline, or use a model that accounts for repeated measurements. These approaches answer related but not identical questions and can rely on different assumptions. The registry record gives baseline and 12 weeks post-intervention as the timeframe, but it does not report which approach was used, whether baseline values were adjusted for, or how repeated measurements were handled.

How should an effect estimate and confidence interval be read?

In general, an effect estimate expresses the contrast targeted by an analysis, such as a difference between group means. A confidence interval describes the uncertainty around that estimate under the method’s assumptions. A relatively narrow interval indicates greater precision than a wide interval, but an interval’s interpretation depends on the chosen contrast and analysis. No effect estimate or confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.

In general, a p-value measures how incompatible the observed data are with a specified null model, assuming the model and analysis are appropriate. It is not the probability that the null hypothesis is true, and it does not describe the size or clinical importance of an effect. The registry record does not report p-values or identify the statistical tests used. A significance threshold or testing strategy for the trial is also not reported in the registry record.

Why do the treatment combinations matter?

The intervention descriptions pair active or placebo vitamin D3 with active or placebo inulin. Such combinations can support distinct questions about each component and about whether their joint effect differs from what would be expected based on their separate effects. In general, assessing an interaction requires an explicitly defined model and contrast. The presence of treatment combinations does not establish that an interaction was tested, and no such test or model is reported in the registry record. It is therefore not possible to infer an additive or synergistic result from the design description alone.

General analysis choices also include whether to compare assigned groups as randomized or to use another analysis population, and how to treat participants who discontinue or lack outcome measurements. An analysis based on assigned groups can preserve the benefits of randomization, while other populations can answer different questions and may be more vulnerable to bias. The registry record does not report the analysis population, participant flow, adherence, or missing-data method. These are not details that can be recovered from the enrollment count alone.

What do planning calculations mean?

General sample-size calculations estimate how much information a study would need under specified assumptions. The planning illustration described for this trial uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is expressed as a fraction of the observed effect. Such assumptions define a calculation, not an outcome. The resulting participant counts, if displayed elsewhere in the statistical report, are planning illustrations and are not observed power. They do not show that the trial had a particular probability of detecting an effect after the data were collected.

The illustration is not the trial’s own design justification. The registry record does not report the protocol’s sample-size justification, its target effect, or any assumptions used when the trial was planned. In addition, interpreting an illustration based on an observed effect requires the observed estimate itself and its uncertainty; those primary outcome results are not reported in the registry record. The planning assumptions should therefore not be mistaken for evidence about the effect or the design rationale.

Multiplicity is another general consideration when an analysis involves several outcomes, time points, or treatment contrasts. Testing many contrasts can increase the chance of at least one apparently notable result unless the analysis plan addresses this issue. The record lists multiple outcome measures and indicates that the primary outcome includes several categories or time points, but it does not report a multiplicity strategy. It also does not report model diagnostics, distributional checks, or sensitivity analyses. Those omissions limit the ability to assess how the analysis was conducted, independently of the fact that numerical endpoint results are not posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and 0 analyses. It identifies the Shannon Index as the primary outcome, and lists changes in gastrointestinal microbiota diversity, richness, and composition among the secondary outcomes. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The record therefore does not give a single primary contrast with an associated estimate.

In general, multiplicity arises when researchers examine several outcomes, time points, or treatment comparisons. Without an analysis plan, it is not possible to tell which comparisons were prespecified, which were considered primary, or whether any adjustment or hierarchical testing approach was used. A multiplicity procedure is not reported in the registry record. This does not establish that no such procedure was used; it means the record does not describe one.

The registry record does not report the number of participants analyzed for the primary or secondary outcomes, the extent or pattern of missing measurements, reasons for missingness, or a method for handling missing data. It also does not identify the analysis population or say how participants who did not complete the intervention were treated analytically. These omissions matter because the available measurements and the analysis population affect what a result would represent.

The enrollment of 40 does not establish how many participants contributed data to each outcome or how they were distributed across treatment groups. The at-risk counts in the adverse-event listing are specific to that listing and should not be treated as primary-outcome analysis counts. A protocol, statistical analysis plan, or fuller results record would be needed to clarify these issues; such details are not reported in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry lists serious and other adverse events by treatment group. For Vitamin D3 and Inulin, 0 serious and 0 other adverse events were reported among 7 participants at risk. For Vitamin D3 and Placebo Inulin, the corresponding figures were 0 and 0 among 8 at risk. For Placebo Vitamin D3 and Inulin, they were 0 and 0 among 7 at risk. For Placebo Vitamin D3 and Placebo Inulin, they were 0 and 0 among 9 at risk. The recorded number of deaths was 0 in each group, and no serious adverse-event terms are listed.

These are event counts for the listed at-risk groups. They do not describe the severity of non-serious symptoms beyond the registry’s category, the timing of events, or the method used to collect and classify them. The registry record does not report further safety-monitoring details. The listed counts also should not be assumed to represent the number analyzed for the primary outcome.

Zero reported events in these groups is a description of the registry entries, not proof that an event is impossible or that a treatment is safe in other settings. The record’s safety figures do not answer the primary microbiota question and do not replace a complete account of adverse-event ascertainment and follow-up.

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

The registry establishes that the trial was designed to study vitamin D3 and inulin, separately and in combination, in the context of cystic fibrosis and dysbiosis. It also identifies a primary measure, the Shannon Index, based on sputum microbiota at baseline and 12 weeks post-intervention. The index represents microbial diversity through both abundance and evenness. These details explain the intended measurement, but they do not establish what the trial found.

The registry record does not report numerical primary-outcome results, treatment contrasts, uncertainty intervals, or p-values. It is therefore not possible to determine from that record whether the Shannon Index changed, whether groups differed, or how precisely any contrast was estimated. The same limitation applies to the listed secondary gastrointestinal microbiota outcomes. Missing posted results should not be converted into a conclusion that an intervention did or did not affect an outcome.

Even if a difference in Shannon Index were available, its interpretation would be specific to this diversity measure and the sampled material. The primary outcome description refers to sputum, while the study aim emphasizes intestinal health. The registry separately lists gastrointestinal microbiota outcomes. A sputum diversity measure does not, on its own, answer every question about gut microbial composition, intestinal function, or clinical status.

General interpretation also depends on the contrast and analysis used. A comparison of combined treatment with both placebos differs from an estimate of the vitamin D3 component, the inulin component, or an interaction between them. The record does not identify which contrasts were tested. The completed status and enrollment count cannot supply that missing information, and the safety counts are not evidence about efficacy.

The result that can be drawn from the registry entry is limited: it documents a completed randomized trial with a stated primary outcome and named intervention combinations, but does not give the numerical outcome findings needed to judge their magnitude or precision. Any stronger conclusion would require results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a study’s broad scientific aim and the measurement chosen as its primary endpoint. The stated aim concerns intestinal dysbiosis and intestinal functions in cystic fibrosis. The primary measure is the Shannon Index from sputum microbiota, while changes in gastrointestinal microbiota diversity, richness, and composition are listed as secondary outcomes. Keeping the sampled material and the scientific question distinct is necessary when interpreting any eventual estimate.

The treatment combinations also make the definition of a comparison important. Active vitamin D3 and active inulin were each paired with their respective placebos, allowing different component questions to be framed. Whether the analysis estimated separate component effects, a combined-regimen contrast, or an interaction is not reported in the registry record. The design alone does not determine which statistical question was answered.

Outcome interpretation depends on both an estimate and its uncertainty. The Shannon Index’s mean and standard deviation describe the outcome, but a treatment comparison requires an explicit contrast and a measure of precision. Because the numerical primary results are not reported, the registry entry illustrates why a clear outcome definition cannot substitute for posted analyses. The record also lists multiple outcomes and time points without reporting a multiplicity approach, analysis population, or missing-data method.

The entry is therefore informative about design and measurement, while limited for evaluating findings. It lets readers identify what the trial set out to assess and where the primary sample came from, but not whether an estimated contrast was large, small, or precise. Separating those design details from unreported results is central to sound interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to interpretation arise from the registry entry. Although the study’s stated goal concerns intestinal health, the primary outcome is described as a sputum microbiota measure. The registry lists gastrointestinal microbiota outcomes separately as secondary outcomes. These measures address related but distinct biological settings, so the primary endpoint should not be treated as a direct measure of every intestinal function named in the study aim.

The primary outcome timeframe is baseline and 12 weeks post-intervention. The record does not describe later follow-up, so it cannot establish whether any measured difference persisted beyond that timeframe. It does not report the primary outcome values, group-specific summary statistics, treatment contrasts, or uncertainty intervals. The outcome description supplies a measure and collection method, but not the results needed to assess effect size or precision.

Enrollment was 40, but the registry entry does not give the number assigned to each treatment group or the number with usable outcome data. The safety listing contains at-risk counts of 7, 8, 7, and 9 for its groups; these are safety figures and do not establish primary-outcome sample sizes. Eligibility criteria and detailed participant characteristics are also not reported in the registry record, limiting assessment of how broadly the findings might apply even if results were available.

The record does not report the analysis plan, exact treatment contrasts, multiplicity handling, analysis population, missing-data methods, adherence, or reasons for unavailable measurements. It also does not state whether the two active components were assessed with an interaction model. These details are necessary to evaluate whether the analysis matches the intended question and how robust a result might be. The completed status and the stated trial design do not resolve these omissions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vitamin D and Prebiotics for Intestinal Health in Cystic Fibrosis — NCT04118010.
• Registry record last updated 2024-02-07; status last verified 2024-01.
• Results first posted 2024-02-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed, randomized, double-masked, parallel, phase 4 trial sponsored by Emory University, with enrollment of 40. The recorded start date is 2020-03-13, and the primary completion date is 2022-12-31. Treatment combinations included vitamin D3, chicory-derived inulin, and their matching placebos; active regimens lasted 12 weeks.

The primary outcome was the Shannon Index of sputum microbiota, measured at baseline and 12 weeks post-intervention. Gastrointestinal microbiota diversity, richness, and composition were listed as secondary outcomes. The record lists 5 outcome measures and 0 analyses, and does not report numerical primary-outcome results, statistical comparisons, or analysis methods.

The adverse-event listing reports 0 serious events, 0 other events, and 0 deaths in each group, with group-specific at-risk counts. These figures are descriptive and separate from the efficacy outcomes. Overall, the registry record documents the trial’s design and measurement plan but does not provide enough outcome analysis to assess the size or precision of treatment contrasts.