Erythromycin in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Erythromycin in Parkinson's Disease (NCT02005029), a randomized na study. The primary outcome is Gastric Emptying Time.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, crossover pilot study registered as NCT02005029, with the title “Erythromycin in Parkinson's Disease.” Virginia Commonwealth University is listed as the sponsor. The registry lists the phase as NA and the study status as completed. The recorded start was 2013-04, and primary completion was 2015-06.

The enrollment was 18. The study compared a one-time intravenous dose of 100 mg erythromycin with a one-time intravenous dose of placebo. A crossover design means that participants receive more than one study condition at different times, so each participant may contribute observations under both conditions. That general feature can make within-participant comparison relevant, but the registry record does not report the treatment sequence, the timing between conditions, or the analysis model used to account for repeated observations.

The primary endpoint was mean gastric emptying time, measured in minutes by SmartPill. Its stated timeframe was 2 weeks, between visits 2 and 3. The analysis description refers to the original ten participants, with one participant's data excluded because symptomatic orthostasis likely confounded the results, one participant withdrawn early due to noncompliance, and four unable to complete a SmartPill evaluation. The reported endpoint summaries each include four observations.

The record also lists motor-function and other secondary outcomes, including hand dexterity, sit-to-stand performance, gait speed, timed up and go, dyskinesia, and MDS-UPDRS Part 3. Their presence indicates that the study registered questions beyond gastric emptying, but the available the registry entries do not provide numerical results for those outcomes. The registry does not report a sample-size justification, detailed statistical plan, or interim-analysis plan.

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: 10 of 18 participants were randomized. Of those not randomized, 7 did not meet eligibility criteria and 1 was withdrawn by the principal investigator prior to randomization due to noncompliance with the protocol.

First Intervention (1 Day)

Reasons for not completing this period:

Washout (2 Weeks)

Second Intervention (1 Day)

Analysis population for the primary outcome, as defined in the registry: Of the original ten participants; one participant's data was excluded due to symptomatic orthostasis which likely confounded her results, one participant was withdrawn early due to noncompliance, and four participants were unable to complete a SmartPill evaluation.

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 Gastric Emptying Time, measured over 2 weeks, between visits 2 and 3.

The primary endpoint was mean gastric emptying time in minutes, measured with SmartPill. Gastric emptying time is a measure of how long stomach contents take to pass out of the stomach. In the study rationale, slow stomach emptying is relevant because the registry describes gastroparesis as common in Parkinson's disease and says it affects how levodopa is absorbed and used by the body.

This endpoint was therefore used to examine a physiological process that could be related to the study's interest in erythromycin and levodopa. It is not itself a direct measure of levodopa absorption, medication exposure, or motor function. Those are distinct outcomes, and the record lists motor-function measures separately among its secondary outcomes. A result on gastric emptying should be interpreted as evidence about that measured process, not as a substitute for those other outcomes.

The stated timeframe was 2 weeks, between visits 2 and 3. The registry describes the summary as a mean with standard deviation. Mean gastric emptying time was 105.0 minutes in the erythromycin condition and 180.0 minutes in the placebo condition; the corresponding standard deviations were 66.5 and 40.6. Each reported summary included four observations. The record says that several people from the original ten did not contribute a SmartPill result, for reasons including symptomatic orthostasis, early withdrawal due to noncompliance, or inability to complete the evaluation.

These endpoint details matter because the observed summaries apply to the analyzed measurements, not automatically to every enrolled participant. The record does not explain the SmartPill measurement protocol in further detail.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports continuous endpoint data as means and standard deviations, alongside a two-sided t-test. These methods answer related but different questions: the mean describes the center of the observed measurements, the standard deviation describes their spread, and the test evaluates how compatible a contrast is with a statistical model of no difference. The record does not report a confidence interval for the comparison.

What does the mean describe?

For a continuous measurement such as gastric emptying time, the arithmetic mean is the sum of the observed values divided by the number of observations. It is a measure of the center of the data. Here the reported means are 105.0 minutes for erythromycin and 180.0 minutes for placebo. These are condition-level summaries; they do not show the individual measurements, how many participants had values above or below either mean, or the pattern of within-participant changes.

The standard deviation summarizes how dispersed the observations are around their mean. It is expressed in the same units as the endpoint. The reported standard deviations are 66.5 and 40.6 minutes. A larger standard deviation indicates more variability in the observed values, but it does not identify why values vary. With only four observations in each reported condition, a standard deviation is itself an uncertain estimate of the underlying variability.

What does the t-test assess?

A t-test compares a mean difference with the amount of variability and the available information in the data. A two-sided test considers departures in either direction rather than specifying only an increase or only a decrease. The registry reports p = 0.036 for a two-sided t-test. Under the test's assumptions and its null model, the p-value indicates how unusual a result at least as incompatible with that null would be. It is not a direct measure of effect size, clinical importance, or the probability that the null model is correct.

A confidence interval, when reported, gives a range of values compatible with the data and a specified procedure. Its width conveys precision: wider intervals indicate less precision. No confidence interval for this comparison is reported in the registry entries, so the uncertainty around the estimated contrast cannot be read directly from such an interval. A p-value alone does not supply that information.

Why does the crossover structure matter?

In a crossover study, a participant may receive both conditions at different times. Measurements from the same person can be correlated because people differ in their typical gastric emptying times. A paired analysis can use within-person comparisons and account for this association. An analysis that treats the conditions as unrelated groups does not use the same structure. The registry calls this study a crossover trial but describes the reported comparison only as a t-test, 2 sided. Whether it was paired, and how sequence or period effects were handled, are not reported in the registry record.

General statistical context: crossover analyses can also be sensitive to effects that carry from one treatment period into another. The registry record does not report the interval between conditions or how potential carryover was addressed. This is a limitation in interpreting the analysis details, not evidence that carryover occurred.

How should variability and a small analysis be read?

The endpoint summaries are based on four observations per condition. With sparse data, individual measurements can have considerable influence on the mean and standard deviation. The observed spread is therefore important context, but neither it nor the p-value can establish how stable the result would be in another sample. General statistical context: when variability exceeds what a simple model anticipates, a model may understate uncertainty. The record does not describe an over-dispersion assessment or an alternative model, and no such issue should be assumed in the registry record.

The registry states that the primary endpoint analysis involved the original ten participants, but it also describes exclusions and inability to complete SmartPill evaluation. The reported summaries each include four observations. The record does not give participant-level data or a missing-data model, so it is not possible to assess the effect of missing measurements on the estimate from these summaries alone.

Overall, means and standard deviations describe the analyzed data, while the reported t-test supplies an inferential comparison under assumptions that are not fully detailed. Statistical interpretation should keep those descriptive and inferential roles separate.

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("Erythromycin", "Placebo")
n   <- c(4, 4)
m   <- c(105, 180)
sp  <- c(66.5, 40.6)
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  Erythromycin  4  105.000  66.500  -0.816  210.816
CARM  Placebo  4  180.000  40.600  115.396  244.604

11. Analyses Reported by the Sponsor

The registry's reported inferential result is a two-sided t-test with p = 0.036. The reported group means are 105.0 minutes for erythromycin and 180.0 minutes for placebo, with standard deviations of 66.5 and 40.6, respectively. Each summary includes four observations. These are the sponsor-reported results recorded for the primary endpoint.

The registry entries do not specify an independently recalculated inferential result or a confidence interval for the comparison. They also do not give enough detail to establish whether the test was paired in keeping with the crossover design. The reported p-value should therefore be read as the test result documented in the registry, not as a separately verified analysis using a fully described model.

No discrepancy between the sponsor-reported result and a recalculation is flagged in the record. That does not supply the missing modeling details or add an independent analysis. In general, when a discrepancy is flagged, the sponsor's own analysis takes precedence; that situation is not indicated by this record. The available information supports describing the sponsor's reported test and the observed summaries, while keeping uncertainty about analysis details explicit.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes involving the 9-hole Peg Test for the right and left hands, the Five Times Sit-to-stand Test, comfortable 20 Feet Gait Speed, comfortable and fast Timed up and go, change in dyskinesia, and MDS-UPDRS Part 3. The record states that nine secondary outcomes were posted and gives counts of 11 outcome measures and 11 analyses. It does not explain the relationship among these counts. Numerical results for the secondary outcomes are not reported in the registry entries.

When a study assesses multiple outcomes or makes multiple comparisons, the chance of obtaining at least one apparently unusual result can increase. Statistical methods can address multiplicity, for example by adjusting the interpretation of p-values or by defining a hierarchy of outcomes. The registry record does not report whether any multiplicity adjustment, outcome hierarchy, or prespecified selection rule was used. The primary endpoint's p-value should therefore not be interpreted as if the status of all other tests were known.

The primary endpoint analysis also has incomplete measurement availability. The registry says it drew on the original ten participants; one participant's data was excluded due to symptomatic orthostasis likely to confound the results, one participant was withdrawn early due to noncompliance, and four participants were unable to complete a SmartPill evaluation. Each reported condition summary includes four observations. The record does not describe imputation, a missing-data sensitivity analysis, or the assumptions used to handle unavailable measurements.

The analysis population is not fully characterized beyond that description. Although enrollment was 18, the primary endpoint summary is based on four observations per condition, and the record does not explain in detail how these participants relate to all enrolled participants or to the crossover analysis set. The registry also does not report whether exclusions were planned before examining results. These omissions limit assessment of potential selection effects and of the generalizability of the endpoint summaries.

These points do not establish that multiplicity or missingness changed the reported result. They identify information that is not reported in the registry record and that readers would need to assess the robustness of the analysis.

13. 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.

Most frequent non-serious adverse event terms

For serious adverse events, the registry reports zero affected participants in the erythromycin group among nine at risk, and zero affected participants in the placebo group among ten at risk. These figures describe the participants recorded as at risk and affected in each group. They do not establish that no serious adverse event could occur, nor do they by themselves provide a precise estimate of comparative safety.

The record also reports other adverse events: four affected participants among nine at risk in the erythromycin group and two among ten at risk in the placebo group. These are listed separately from serious adverse events. The registry entries do not provide event descriptions for these other adverse events, their timing, severity, or relationship to study treatment. The numbers should not be interpreted as counts of distinct event episodes; the listed figures concern affected participants.

Death counts are not reported in the registry record. The adverse-event figures are small and do not support a broad safety conclusion. In addition, this was a crossover study, and the record does not provide detail on how adverse-event exposure periods were assigned or how risk was summarized. The figures are best read as the registry's reported counts, with the available denominators and missing context kept in view.

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

The registry reports lower mean gastric emptying time in the erythromycin condition than in the placebo condition: 105.0 minutes versus 180.0 minutes. The corresponding standard deviations were 66.5 and 40.6, and each condition summary included four observations. A two-sided t-test is reported with p = 0.036. Those details describe the primary endpoint result in the analyzed data.

The result does not directly demonstrate an effect on levodopa absorption or motor function. The study rationale links gastric emptying to levodopa absorption and use, but gastric emptying time is a separate measurement. The registry lists motor-function measures as secondary outcomes, but numerical results for those measures are not reported in the registry entries. Consequently, the primary endpoint result should not be presented as a finding about those unreported outcomes.

The result also does not establish a precise or broadly applicable treatment effect. The primary endpoint summaries are based on a small number of observations, several SmartPill evaluations were unavailable, and the registry does not provide a confidence interval for the comparison. Nor does it describe in detail how the t-test accounted for the crossover structure. These gaps leave uncertainty about precision and analysis assumptions.

A p-value is not a measure of clinical importance and does not tell readers the probability that a hypothesis is true. The registry record also does not report a sample-size justification, statistical analysis plan, or multiplicity approach. These details are relevant when judging how much weight to place on a pilot result alongside other evidence.

In general, a pilot study can provide preliminary information about a measurement and a possible signal that merits further examination. That general role should not be confused with proof of a treatment effect. The record supports describing the observed means and the sponsor-reported test; it does not settle questions about repeatability, clinical outcomes, or application to people beyond those represented by the analyzed measurements.

15. Why This Trial Matters Statistically

This study raises several statistical issues that are important in clinical research. It is described as randomized, double-blind, and crossover, yet the registry reports a two-sided t-test without specifying whether it used a paired comparison. In crossover studies, measurements from the same participant are related. Whether an analysis uses that relationship can affect both the estimate's uncertainty and the interpretation of its test result.

The primary endpoint was measured with SmartPill, and the record explains that multiple participants from the original ten did not contribute a completed evaluation. The reported condition summaries each include four observations. This makes the relationship between enrollment, eligibility for the primary analysis, and measurement completion important to understand. The record describes some reasons for unavailable data but does not report a missing-data strategy or sensitivity analyses.

The reported means and standard deviations convey both the direction of the observed summaries and their variability. The p-value supplies a model-based comparison, but without a confidence interval or fuller analysis description, the precision and robustness of that comparison are difficult to assess. The study also lists secondary outcomes, while multiplicity handling and numerical secondary results are not reported in the registry entries.

These are not merely technical details. They shape what can be concluded from a small pilot study and help distinguish a preliminary observed pattern from a result that is well characterized and reproducible. The record provides useful information about the intervention, endpoint, and reported test, while leaving important analysis details unresolved.

16. 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 are specific to this record. The primary endpoint analysis is described as involving the original ten participants, with one participant's data excluded because symptomatic orthostasis likely confounded the results, one withdrawn early due to noncompliance, and four unable to complete a SmartPill evaluation. The two condition summaries each include four observations. The record does not fully explain how these observations map to participants in the crossover analysis or how unavailable measurements were handled.

The registry identifies the design as crossover but reports only a two-sided t-test for the primary comparison. It does not state whether the test was paired, how treatment order or period was handled, or whether potential carryover was considered. These omissions make it difficult to evaluate whether the inferential method reflects the design.

The registry does not report a confidence interval, a sample-size justification, or a detailed statistical analysis plan. It also does not report a multiplicity adjustment for the listed secondary outcomes. Numerical secondary-outcome results are not reported in the registry entries, so the record does not allow a complete view of the outcome pattern.

The adverse-event figures are brief: serious adverse events are reported as zero affected participants in each group, other adverse events are counted, and death counts are not reported in the registry record. Descriptions, timing, and treatment relatedness for the other adverse events are not included in the registry record. These limitations constrain interpretation of both the efficacy-related endpoint and the safety information, without showing that any particular omitted detail would change the result.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Erythromycin in Parkinson's Disease — NCT02005029.
• Registry record last updated 2017-02-03; status last verified 2016-12.
• Results first posted 2017-02-03.
• 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.

20. Record Summary

NCT02005029 is a completed, randomized, double-blind crossover pilot study sponsored by Virginia Commonwealth University. It compared a one-time intravenous dose of 100 mg erythromycin with a one-time intravenous dose of placebo in a study of Parkinson's disease and levodopa. Enrollment was 18; the recorded start was 2013-04 and primary completion was 2015-06.

The primary endpoint was SmartPill-measured mean gastric emptying time in minutes, with a stated timeframe of 2 weeks, between visits 2 and 3. The registry reports means of 105.0 for erythromycin and 180.0 for placebo, standard deviations of 66.5 and 40.6, and four observations in each condition summary. A two-sided t-test is reported with p = 0.036.

The record describes unavailable and excluded SmartPill evaluations, but does not fully specify the crossover analysis, missing-data methods, confidence interval, sample-size justification, or multiplicity approach. Numerical secondary-outcome results are not reported in the registry entries. These details limit how fully the reported primary result can be assessed.