Oral Propionate to Treat and Prevent Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Oral Propionate to Treat and Prevent Diabetes (NCT01692002), a randomized na study. The primary outcome is Propionate CMax.

2. Clinical Question

The clinical question has several parts, and the primary outcome addresses only the pharmacokinetic part. A peak concentration describes the highest plasma concentration captured in the measurement schedule; it does not directly measure glucose tolerance or insulin response. The registry separately lists secondary outcomes related to insulin response and describes oral and intravenous glucose-tolerance procedures. Those outcomes could address different physiological questions, but their numerical results and analyses are not reported in the registry record.

The registry's stated aims include determining a pharmacokinetic profile, examining dose and glucose tolerance, and investigating potential mechanisms. These aims should not be treated as evidence that each question was answered. The available primary outcome summaries describe concentrations, while the registry records no analyses for the outcomes. The reason the study was terminated and whether all planned assessments were completed are not reported in the registry record.

3. Trial Design

The registry describes a randomized, triple-masked crossover study sponsored by Imperial College London. Sodium propionate and sodium chloride are the listed intervention conditions. In a crossover design, a participant may receive more than one condition in sequence, allowing comparisons within participants; this is a general description of the design, not confirmation of the sequence used in this study. The registry does not report the treatment order, allocation method, masking roles, washout interval, or any period-specific procedures.

The study description separates the work into pharmacokinetic, oral glucose tolerance, and intravenous glucose tolerance studies. The arm descriptions associate both sodium propionate and sodium chloride with each of these activities. The primary outcome belongs to the pharmacokinetic assessment: peak plasma propionate concentration measured by mass spectrometry. The registry describes measurements at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, and 8h. It says the mean was estimated first per patient across those measurement times and then per arm across the 6 patients.

Enrollment is recorded as 6, and the posted outcome summaries list 3 participants for each intervention. The registry status is TERMINATED. The recorded study start is 2013-01 and primary completion is 2019-08. The reason for termination, actual completion status of individual study components, and participant flow are not reported in the registry record. The listed phase is NA.

Randomization and masking can help limit allocation and assessment biases, but their presence in a registry description does not establish how successfully they were implemented. In a crossover study, treatment order, time effects, and possible carryover can also matter to interpretation. The record does not give enough detail to assess these features or identify the analysis used to account for them. The design label alone does not establish that the reported summaries represent a valid paired treatment comparison.

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.

Before assignment: Wash out of 7 days between interventions

1st Period of the Cross-over Study

Washout Period

2nd Period of the Cross-over Study

Analysis population for the primary outcome, as defined in the registry: Propionate concertation in plasma

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: only 6 where recriuted and completed

6. Primary Endpoint

The registry lists the primary outcome as Propionate CMax, measured over hours (up to 8hrs).

Propionate CMax is the primary outcome. It is intended to represent peak plasma concentration of propionate after oral administration, with concentration measured in mmol/l. Pharmacokinetic outcomes help describe how a substance appears in the circulation over time. A peak concentration can indicate the highest measured exposure in the sampling schedule, while the measurement times provide context for how that peak was identified.

The registry describes mass-spectrometry measurements at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, and 8h. It also specifies that the mean was first estimated per patient across all listed time points, then summarized per arm across the 6 patients. Thus, the posted arm summaries are not described as a mean of a single common time-point measurement. The record does not clarify how the peak was selected for each participant or whether any measurements were missing.

A peak concentration is useful for characterizing exposure, but it is not itself a measure of glucose tolerance, insulin secretion, diabetes prevention, or clinical benefit. The record's broader aims include glucose-tolerance testing and investigating insulin-related mechanisms, but those questions require their own outcome data and analyses. Numerical results for the listed secondary outcomes are not reported in the registry record. The primary outcome summary therefore addresses a limited pharmacokinetic question and cannot by itself resolve the broader aims.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

As a general statistical point, a continuous outcome such as plasma concentration can be summarized by a mean and a measure of spread. The mean describes the average on the outcome's measurement scale. The standard deviation describes how much individual observations vary around that mean. They answer different questions: a small standard deviation does not necessarily mean the mean is estimated precisely, and a large standard deviation does not by itself show that a treatment contrast is absent.

For Propionate CMax, the registry reports means and standard deviations for the Sodium Chloride Capsule and Sodium Propionate Capsule arms. The measurement unit is mmol/l. The reported values are 7.2 with standard deviation 0.26 and 7.79 with standard deviation 0.25, respectively. Each arm summary has n=3. These summaries are descriptive and do not provide a direct estimate of the uncertainty around the difference between conditions.

A confidence interval is a general way to express uncertainty around an estimated quantity, such as a mean or treatment contrast. It gives a range of values compatible with the data and the assumptions of the statistical method. The registry does not report a confidence interval for this primary outcome. It also does not report a p-value or an inferential comparison. The recalculated comparison is not available because values are missing or not estimable for a continuous two-arm comparison. Without an inferential estimate and its uncertainty, the arm summaries alone cannot establish how precisely any contrast is estimated.

The crossover label has important analytical implications. As a general matter, crossover designs can compare treatment conditions within the same participant, which can account for stable differences between participants. That approach requires information linking each participant's outcome under each condition. The registry record does not report participant-level paired outcomes, the order of treatment, the period structure, or the method used to handle period or carryover effects. It therefore does not support a conclusion that the posted arm summaries are a paired analysis. The statistical plan is not reported in the registry record.

The endpoint description says mass-spectrometry measurements were scheduled at -10, 0, 15, 30, 60, 90, 120, 150, 180, 4h, 6h, and 8h. It says the mean was estimated per patient across all listed times, and then per arm across the 6 patients. This makes the construction of the posted outcome consequential: a peak concentration and an average across measurements are not interchangeable concepts. The record calls the outcome Propionate CMax and describes it as peak plasma concentration, but does not specify the exact participant-level calculation used to derive the summary. That detail is not reported in the registry record.

As a general matter, repeated measurements may be correlated within a participant. A statistical analysis of measurements over time can account for that dependence, while reducing measurements to a participant-level summary can avoid treating each time point as an independent participant. The registry describes a per-patient summary before an arm-level mean, but does not report a model, the handling of missing time points, or whether all listed measurements contributed for every participant. No further method should be inferred from the description.

Small enrollment affects how much information the data can carry. With enrollment recorded as 6 and n=3 in each arm summary, individual observations may have substantial influence on the means and standard deviations. This is a general consideration, not a calculation of power or a claim about the unobserved participant values. The registry does not report a sample-size justification or a protocol-based target. The method used to choose enrollment is not reported in the registry record.

Planning illustrations, when based on an observed effect, are not observed power and do not substitute for a prospective design rationale. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry does not report its own design justification, and no actual planning-illustration values are included in the record described. Such illustrations would be conditional on their assumptions and on the observed effect being a suitable planning basis; they do not show that the study had a particular probability of detecting an effect.

Multiplicity is a general concern when several outcomes or analyses are considered, because repeated testing can increase the chance of at least one apparently notable result. The registry lists 4 outcome measures and 3 secondary outcomes, but records 0 analyses. No hierarchy of outcomes, multiplicity adjustment, or prespecified analysis plan is reported in the registry record. The number of listed outcomes alone does not establish how many statistical tests were conducted.

For continuous outcomes, an analysis plan would ordinarily clarify the target contrast, the analysis population, handling of missing observations, and the model or summary method. For a crossover study, it would also specify whether within-participant pairing and treatment periods are incorporated. These details are not reported in the registry record. The registry summaries therefore support a descriptive reading of the posted values, not reconstruction of an unreported statistical analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Sodium Chloride Capsule", "Sodium Propionate Capsule")
n   <- c(3, 3)
m   <- c(7.2, 7.79)
sp  <- c(0.26, 0.25)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Sodium Chloride Capsule  3  7.200  0.260  6.554  7.846
CARM  Sodium Propionate Capsule  3  7.790  0.250  7.169  8.411

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures and 3 secondary outcomes. The secondary outcomes concern insulin stimulated by propionate, the insulinogenic index, and insulin levels across time points. It records 0 analyses. Numerical results for the secondary outcomes, any prioritization among outcomes, and any multiplicity procedure are not reported in the registry record.

As a general statistical principle, considering multiple outcomes can complicate interpretation because the chance of an apparently notable result may rise when many tests are conducted. A prespecified hierarchy or adjustment can help define how results should be interpreted. The registry record does not report whether such an approach was planned or used. The listed outcome count does not establish the number of tests performed, particularly when no analyses are recorded.

Missing-data handling is also not reported in the registry record. The endpoint description identifies several scheduled measurement times and describes an average calculated per patient before an arm-level summary, but does not say whether every participant had data at every time, how missing measurements were handled, or how many participants contributed to each calculation beyond the posted arm summaries.

The analysis populations are not described. The registry does not state whether the primary outcome summaries include all randomized participants, only participants with available measurements, or another defined group. Nor does it report a plan for handling incomplete crossover participation. These omissions limit evaluation of potential selection bias and make it difficult to determine exactly which participants the estimates represent.

12. 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.

The registry reports serious adverse events for the Sodium Chloride Pill and Sodium Propionate Pill groups. For each group, serious events affected 0 participants among 3 at risk, and deaths were 0. Other adverse events affected 0 participants among 3 at risk in each group. No top serious-event terms are listed.

These are counts recorded in the registry, not proof that no adverse events occurred under every definition or during every period. The record does not report the definitions used, the observation window, the method of collection, or whether events were assessed by treatment period. It also does not explain how safety observations were handled in the crossover design. The reported at-risk counts should be read as the registry presents them, without treating them as evidence about participants outside the recorded groups.

With a recorded enrollment of 6, the absence of reported events is limited information about safety. Rare or delayed events cannot be evaluated from these counts alone, and the registry does not provide a comparative statistical analysis of adverse events. The figures describe what is posted for the two groups; they do not establish that either intervention is free of risk.

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

The posted results provide descriptive pharmacokinetic summaries for sodium propionate and sodium chloride. The mean Propionate CMax is 7.2 mmol/l with standard deviation 0.26 in the Sodium Chloride Capsule arm, and 7.79 mmol/l with standard deviation 0.25 in the Sodium Propionate Capsule arm. These figures describe the recorded outcome summaries; they are not an inferential finding about a treatment effect.

The registry does not report a confidence interval, p-value, or estimable comparison for this primary outcome. It also does not report numerical analyses for the listed insulin-related secondary outcomes. As a result, the record cannot establish how precise a contrast between interventions would be, whether the primary outcome differs statistically, or what the glucose-tolerance and insulin findings were.

The primary outcome is a plasma concentration measure. It does not directly demonstrate a change in glucose tolerance, insulin secretion, diabetes prevention, or another clinical outcome. Those broader topics appear in the study aims and intervention descriptions, but results for them are not reported in the registry record. The study status is TERMINATED; the reason for termination and its effect on the planned research are not reported.

The crossover design could in principle allow within-participant comparisons, but the record does not provide the sequence, paired data, or analysis details needed to assess whether such a comparison was made. The observed arm summaries should therefore not be read as a definitive comparison. They are limited descriptions of the posted data, based on the recorded participants and outcome calculation.

Nothing in the available record supports a conclusion that sodium propionate does or does not improve glucose tolerance, alter insulin response, prevent diabetes, or produce a particular safety profile. Those questions require relevant outcome results, a suitable analysis, and enough information to assess uncertainty. The posted means and event counts do not supply that evidence on their own.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between pharmacokinetic evidence and evidence about clinical or physiological outcomes. A peak plasma concentration can characterize exposure, while glucose-tolerance and insulin measures address different questions. Because the registry's broader aims include both, keeping the outcome domains separate is essential to avoid reading a concentration summary as an answer to every study objective.

The crossover label also highlights the importance of design-specific analysis. In general, comparisons within participants can differ from comparisons treating groups as independent, because the same participant contributes observations under multiple conditions. Treatment sequence, period effects, carryover, and paired observations can therefore matter. The registry identifies a crossover design but does not report the details needed to assess its analysis. This is a reminder that a design label alone does not reveal how the data were modeled.

The record additionally illustrates why descriptive estimates should be read together with uncertainty. The posted means and standard deviations summarize the available outcome, but a confidence interval or inferential comparison is not reported. The enrollment and arm summaries are small, and the registry records no analyses. A reader therefore cannot assess the precision of a contrast or connect it statistically to the broader aims.

Finally, the registry lists several outcome measures but does not report results for the insulin-related outcomes. That gap makes prespecification, outcome hierarchy, missing-data handling, and transparent reporting especially relevant general considerations. The trial matters statistically not because its record resolves the biological questions, but because it shows how design, outcome definition, analysis reporting, and uncertainty determine what can responsibly be concluded from posted clinical research.

15. Limitations

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

The main limitation for interpretation is the absence of an estimable inferential comparison for the continuous primary outcome. The record gives arm means and standard deviations, but no confidence interval or p-value. Participant-level data are not reported, so the summaries cannot be independently assessed or used to reconstruct a crossover comparison.

The outcome construction is not fully specified. The registry describes Propionate CMax as peak concentration, gives a measurement schedule, and says the mean was estimated per patient across all time points before being summarized by arm. It does not explain the exact peak calculation or the handling of missing measurements. The relationship between that description and the posted arm-level summaries is therefore not fully clear.

Although the design is labeled randomized, triple-masked, and crossover, treatment order, masking roles, washout, period effects, carryover, and the analysis of paired observations are not reported in the registry record. Participant flow, completion by study component, eligibility criteria, and analysis populations are also not reported. These omissions prevent assessment of whether the posted summaries represent all randomized participants or a subset.

The record lists 4 outcome measures and 3 secondary outcomes, but no analyses. Numerical results for the secondary insulin outcomes are not reported. A statistical analysis plan, multiplicity approach, missing-data method, and sample-size justification are not reported in the registry record. The status is TERMINATED, but the reason and its implications for data collection are not reported.

Finally, enrollment is recorded as 6, and the posted arm summaries have n=3 each. The limited amount of information, together with the absence of uncertainty estimates and analysis details, constrains conclusions about the primary outcome, the broader glucose-tolerance aims, and safety. The record supports a descriptive account, not a definitive assessment of treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Oral Propionate to Treat and Prevent Diabetes — NCT01692002.
• Registry record last updated 2025-06-18; status last verified 2025-06.
• Results first posted 2025-06-18.
• 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.

19. Record Summary

The registry record describes NCT01692002, titled “Oral Propionate to Treat and Prevent Diabetes,” sponsored by Imperial College London. It is listed as randomized, triple-masked, and crossover, with enrollment of 6. The recorded status is TERMINATED; the recorded start is 2013-01 and primary completion is 2019-08.

The study compares sodium propionate with sodium chloride and describes pharmacokinetic, oral glucose-tolerance, and intravenous glucose-tolerance assessments. The primary outcome is Propionate CMax, a plasma concentration measure reported as mean and standard deviation in mmol/l over hours (up to 8hrs). Posted arm summaries are 7.2 with standard deviation 0.26 for sodium chloride and 7.79 with standard deviation 0.25 for sodium propionate, with n=3 in each arm.

The registry records 4 outcome measures, 3 secondary outcomes, and 0 analyses. It does not report an estimable inferential comparison for the primary outcome or numerical analyses for the secondary outcomes. The reason for termination and key analysis details are not reported in the registry record.