Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor Functions in Patients With Irritable Bowel Syndrome (IBS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor Functions in Patients With Irritable Bowel Syndrome (IBS) (NCT01253408), a randomized phase 2 study. The primary outcome is Colonic Transit Geometric Center at 24 Hours.

2. Clinical Question

3. Trial Design

The registry record describes a completed, randomized, double-masked, parallel-group phase 2 trial sponsored by Mayo Clinic. Enrollment was 36. The record lists three arms: dronabinol 2.5 mg twice daily, dronabinol 5 mg twice daily, and placebo. Each assigned treatment was taken orally with water twice per day for two days.

The posted primary outcome summaries include 10 participants in the 2.5 mg arm, 13 in the 5 mg arm, and 13 in the placebo arm. For the primary outcome and the posted secondary measures, the registry record gives group means and standard deviations. The posted comparisons contrast each dose group with placebo.

The trial focused on physiological measurements of gastrointestinal and colonic function. The brief summary describes an investigation of how dronabinol affects the movement of food through the stomach and colon in people with D-IBS, and proposes that effects on colonic movement may be related to genes controlling relevant receptors. The record does not report results about genetic subgroups or a genetic analysis.

The registry record gives a start date of 2009-09 and a primary completion date of 2011-12, and marks the study as completed. Further details about eligibility criteria, allocation procedures, masking procedures, treatment adherence, and the original statistical 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

Reasons for not completing this period:

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 Colonic Transit Geometric Center at 24 Hours, measured over 24 hours.

The primary endpoint was colonic transit geometric center at 24 hours, reported as a mean with a standard deviation. It is a continuous measure derived using scintigraphy. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed-release capsule. Anterior and posterior gamma images are taken hourly, and the geometric center is calculated as a weighted average of counts across colonic regions.

The scale ranges from 1 to 5. A geometric center of 1 means all isotope is in the ascending colon, while a value of 5 means all isotope is in the stool. Higher values indicate faster colonic transit. This makes the endpoint a quantitative measure of movement through the colon rather than a direct measure of symptoms. It was used to assess the study’s central physiological question: whether the assigned dronabinol doses were associated with different colonic transit measurements than placebo.

The registry record reports the measurement timeframe as 24 hours. It does not report an analysis linking this endpoint to symptom relief, quality of life, or longer-term outcomes. The endpoint therefore describes transit under the study’s measurement conditions; its meaning should not be extended to outcomes that were not reported.

7. Results Posted in the Registry

• Dronabinol 2.5 mg Bid: mean 3.12 versus 2.77 on control; difference 0.35 (95% CI -0.69 to 1.39), standardized effect d = 0.28; z-test p = 0.510.
• Dronabinol 5 mg Bid: mean 3.05 versus 2.77 on control; difference 0.28 (95% CI -0.59 to 1.15), standardized effect d = 0.25; z-test p = 0.528.

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.

Gastric Emptying Half-Time (t1/2)

• 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:
  • Dronabinol 2.5 mg Bid: mean 137.30 versus 138.20 on control; difference -0.90 (95% CI -33.07 to 31.27), standardized effect d = -0.02; z-test p = 0.956.
  • Dronabinol 5 mg Bid: mean 130.70 versus 138.20 on control; difference -7.50 (95% CI -41.08 to 26.08), standardized effect d = -0.17; z-test p = 0.662.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 2.5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.

Colonic Filling at 6 Hours

• 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:
  • Dronabinol 2.5 mg Bid: mean 48.60 versus 57.46 on control; difference -8.86 (95% CI -33.74 to 16.02), standardized effect d = -0.31; z-test p = 0.485.
  • Dronabinol 5 mg Bid: mean 51.62 versus 57.46 on control; difference -5.84 (95% CI -26.94 to 15.26), standardized effect d = -0.21; z-test p = 0.588.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 2.5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.

Ascending Colon Emptying T 1/2

• 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:
  • Dronabinol 2.5 mg Bid: mean 9.50 versus 14.53 on control; difference -5.03 (95% CI -10.40 to 0.34), standardized effect d = -0.72; z-test p = 0.066.
  • Dronabinol 5 mg Bid: mean 9.90 versus 14.53 on control; difference -4.63 (95% CI -10.05 to 0.79), standardized effect d = -0.66; z-test p = 0.094.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 2.5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dronabinol 5 mg Bid and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover related aspects of gastrointestinal function: gastric emptying half-time, colonic filling at 6 hours, ascending colon emptying, and gastric emptying at 2 and 4 hours, as well as a listed colonic transit measure. Numerical summaries are posted for gastric emptying half-time, colonic filling at 6 hours, and ascending colon emptying. Numerical results for other named secondary outcomes are not reported in the registry record.

Across the secondary measures with numerical results, the reported comparisons vary in direction and magnitude. The estimates and their uncertainty should be interpreted as exploratory context for the primary transit result, not as a single coherent test of one outcome. These measures capture different time points and physiological processes, so a finding on one does not automatically imply a corresponding finding on another.

The secondary results also do not remove the uncertainty in the primary comparison. They are based on the same small study and include multiple outcome comparisons. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the outcomes. Without such information, unadjusted secondary results carry less weight than a result from a clearly specified primary analysis, particularly when several outcomes are examined.

Statistical interpretation should emphasize the size and precision of each contrast rather than treating a p-value as a pass-or-fail label. The record does not report formal secondary analyses, and the posted summary statistics cannot establish whether any observed pattern reflects a stable underlying difference. These related endpoints are best read as additional descriptive measurements within a limited study, rather than independent confirmations.

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

• Colonic Transit Geometric Center
• Gastric Emptying Half-Time (t1/2)
• Colonic Filling at 6 Hours
• Ascending Colon Emptying T 1/2
• Gastric Emptying at 2 and 4 Hours

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measure, and the registry record reports a mean and standard deviation for each arm. A mean describes the group’s average measurement. A standard deviation describes how dispersed individual measurements are around that average; it is not a confidence interval and does not directly quantify the uncertainty in the group mean.

The posted comparisons express the mean difference between each dronabinol dose and placebo. For the primary endpoint, the contrast is the treatment-group mean minus the placebo mean. A positive difference therefore corresponds to a higher mean geometric center in the dronabinol group, which indicates faster colonic transit on this scale. The reported estimates are 0.35 for dronabinol 2.5 mg and 0.28 for dronabinol 5 mg, each compared with placebo.

The confidence interval gives a range of values compatible with the estimate under the calculation’s assumptions. For the primary comparisons, the intervals are -0.692 to 1.392 and -0.589 to 1.149. Because each interval extends across zero, the estimates are not sharply distinguished from no group difference by these data. The intervals also allow for differences in either direction, so the point estimates should not be interpreted as precise measures of the underlying contrast.

The p-values attached to these comparisons are unadjusted: 0.51 for 2.5 mg and 0.528 for 5 mg. A p-value describes how unusual the data, or more extreme data, would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a contrast. A p-value should be considered alongside the estimate, interval, design, and analysis context. In this record, the original inferential analysis and its prespecified details are not reported in the registry record.

General statistical context: confidence intervals and p-values rely on an analysis model and its assumptions. For continuous outcomes, common approaches use assumptions about the distribution of measurements and the independence of observations. The registry record does not report enough detail to determine the full model or any adjustments used in the trial’s original analysis. The posted arm summaries alone do not reveal the distribution of individual observations or whether there were departures from model assumptions.

The study used three parallel groups: two active doses and placebo. Comparing each active group with the same placebo group creates multiple contrasts, while the trial also includes multiple outcomes. When several comparisons are examined, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. Whether the trial planned a strategy to address this issue is not reported in the registry record. For this reason, isolated unadjusted secondary p-values, where available, warrant particular caution.

General statistical context: small samples can make estimates sensitive to individual observations and can yield wide confidence intervals. The primary group sizes were 10, 13, and 13. Those counts help explain why the estimates should be interpreted with attention to precision, but do not by themselves establish that any particular result is biased. The posted summaries do not allow assessment of individual-level distributions, missing outcome values, or the influence of particular observations.

The planning illustrations use an observed-effect-based calculation, rather than reconstructing the trial’s original design. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is set to a stated fraction of the observed effect. This is a planning exercise only. The original sample-size justification and assumptions are not reported in the registry record.

General statistical context: over-dispersion means that variability is greater than a chosen model anticipates. When present, it can make standard errors based on an under-dispersed model too small and intervals too narrow. The posted continuous outcomes are reported with standard deviations, but the registry record does not report a separate over-dispersion assessment. The individual-level data needed to examine that issue are not reported in the registry record.

The record lists six outcome measures and provides numerical summaries for the primary endpoint and three secondary measures. It lists no reported analyses for the secondary outcomes. The registry record does not describe an intention-to-treat or per-protocol population, missing-data methods, covariate adjustment, interim analyses, or a detailed statistical analysis plan. These omissions limit the ability to determine how the posted summaries relate to the trial’s planned analysis.

11. Confidence Intervals and Precision

The primary comparisons are uncertain relative to their point estimates. For dronabinol 2.5 mg versus placebo, the mean difference was 0.35, with a confidence interval from -0.692 to 1.392. For dronabinol 5 mg versus placebo, the mean difference was 0.28, with a confidence interval from -0.589 to 1.149. Both intervals include zero and extend into both negative and positive values.

In practical statistical terms, the intervals do not isolate one direction of difference. They are compatible with a lower geometric-center mean in the active group, little or no difference, or a higher mean. Since higher geometric-center values indicate faster colonic transit, the range of possible contrasts corresponds to uncertainty about both the direction and size of the transit difference. The group means alone do not convey this uncertainty; the interval is important context for reading the point estimate.

The standard deviations for the primary outcome were 1.29, 1.02, and 1.23 in the 2.5 mg, 5 mg, and placebo groups, respectively. These describe variation among measurements within each group, while the confidence intervals describe uncertainty around the between-group contrasts. The two concepts answer different questions.

There are no reported sponsor analyses or interval estimates from a prespecified statistical model in the registry record. The posted comparison intervals and p-values are unadjusted calculations. They do not account for multiple outcomes or multiple dose comparisons. The record also does not report individual-level data, missing-data handling, or the assumptions of an original analysis, so the precision figures should be interpreted in that limited context.

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 planning figures are expressed as participants per arm, not as total trial enrollment or total events. They illustrate how many participants per arm would be needed under the stated calculation assumptions to detect an effect set to a specified fraction of the observed effect. The figures are not the number enrolled in this trial.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is set to 100%, 75%, or 50% of the observed effect, depending on the planning scenario. For each scenario, the 80% power column gives the participants per arm associated with an 80% chance of detecting that specified effect under those assumptions; the 90% power column gives the corresponding count for a 90% chance. These are design-planning quantities, not guarantees about what a future study will observe.

Smaller effects require more participants because they are harder to distinguish from random variation at a given level of uncertainty. Consequently, the planning figures increase as the target moves from the full observed effect to smaller fractions. Some estimates can be especially large when the observed contrast is small relative to the variability in the outcome.

These calculations are based on observed effects and do not reveal the reasoning behind the original enrollment target. The original trial’s sample-size justification and design assumptions are not reported in the registry record. This is not observed power: it is a planning illustration, not a retrospective measure of the trial’s success or a probability that its findings are correct.

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 = 0.350; pooled standard deviation σ = 1.256.
2. n = 2 × (1.96 + 0.842)² × 1.256² / 0.350² = 202.2, rounded up to 203 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 <- 0.35                      # observed difference in means
sigma <- 1.2560652849275                     # 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(1253408)
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 = 203 (80% power), 271 (90% power)
 75% of observed effect: n per arm = 360 (80% power), 482 (90% power)
 50% of observed effect: n per arm = 809 (80% power), 1,083 (90% power)
power.t.test: 203.1 
Simulated power at n = 203 per arm: 0.799 (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 record identifies a primary endpoint and multiple secondary outcomes, and the trial compares two dronabinol doses with a shared placebo group. This creates several possible comparisons. When several outcomes or contrasts are assessed, unadjusted testing can increase the chance that at least one result appears notable by chance alone. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a plan for interpreting multiple comparisons.

The record does not report a detailed statistical analysis plan, including whether covariates were to be included, which analysis model was planned, or how the primary endpoint would be handled if observations were missing. It also does not report interim analyses. These details should not be inferred from the posted group summaries.

Analysis populations are not described. The registry record does not say whether the posted results use an intention-to-treat population, a per-protocol population, or another defined set of participants. It does not report participant-level exclusions, the number with missing values for each outcome, or any method for handling missing data. Consequently, the reported arm sizes do not establish whether all enrolled participants contributed to every outcome.

The record lists no reported analyses for the secondary outcomes. It supplies group summaries and comparison statistics for some measures, but does not describe whether those comparisons were prespecified or adjusted. These gaps limit the ability to distinguish confirmatory analyses from descriptive or exploratory calculations. The primary outcome remains identifiable from the registry record, but the broader inferential framework is not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures list 0 affected participants among 10 at risk in the dronabinol 2.5 mg group, 0 among 13 at risk in the dronabinol 5 mg group, and 0 among 13 at risk in the placebo group. The registry record lists no serious adverse event terms. Death counts are not reported in the registry record.

The figures for participants affected by other adverse events are 7 of 10 in the 2.5 mg group, 9 of 13 in the 5 mg group, and 7 of 13 in the placebo group. These counts describe the posted adverse-event categories; they do not by themselves establish causation or permit a detailed comparison of event types or severity. The registry record does not provide a list of the other adverse events in this summary or further information about their timing or duration.

These safety counts should be read in the context of a short, two-day treatment period and the small numbers of participants in each group. They are a record of reported events during the study, not a complete assessment of longer-term safety.

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

The primary outcome provides a numerical measure of colonic transit over the study’s 24-hour measurement period. The mean geometric center was higher in each dronabinol group than in the placebo group, and the posted unadjusted mean differences were positive. The confidence intervals are broad and include zero, however, so the estimates do not precisely determine the direction or size of the group differences.

These data do not establish that the groups differed, nor do they establish that the groups were equivalent. A non-significant unadjusted p-value is not evidence that the true difference is exactly zero. Equivalence would require a prespecified margin and an analysis designed to assess whether the interval lies within that margin; such a margin and analysis are not reported in the registry record.

The measurements concern physiological outcomes, not direct evidence about abdominal pain or other symptom changes. The registry record does not report results for symptom relief, quality of life, or longer-term outcomes. The brief summary describes a hypothesis involving receptor-related genes, but genetic findings are not reported in the registry record. No conclusion about genetic regulation can therefore be drawn from these posted results.

The trial was completed and enrolled 36 participants, with small group sizes for the primary outcome. The posted estimates are informative as measurements from this study, but their uncertainty and the absence of details about the planned analysis limit broader interpretation. They do not establish how results would generalize beyond the participants and brief treatment period described in the registry record.

In general, a statistical result describes evidence in a particular study under its design and analysis assumptions. It is not a substitute for clinical judgment, and these findings alone do not determine what treatment is appropriate for any individual. The registry record supports a cautious description of measured group outcomes, rather than a conclusion about treatment benefit or lack of benefit.

17. Why This Trial Matters Statistically

This trial illustrates why an observed difference and the precision of that difference need to be considered together. The primary group means are not identical, but the uncertainty around both dose-versus-placebo contrasts is substantial and includes zero. Reporting only the mean differences, or only the p-values, would leave out important information about how much the data can distinguish among possible effects.

The outcome is also a useful example of interpreting a scale in its biological direction. Because higher geometric-center values indicate faster colonic transit, the sign of a contrast has a defined measurement meaning. That interpretation remains limited to the endpoint itself: it does not automatically translate into a symptom or clinical outcome.

The trial’s multiple arms and several physiological outcomes raise questions about how comparisons were planned and interpreted. The registry record identifies the primary outcome but does not report a complete analysis plan or multiplicity strategy. This makes it important to separate the primary endpoint from additional measurements and to avoid treating multiple unadjusted results as independent confirmation.

Finally, the planning illustrations show how strongly sample-size requirements depend on the effect selected for detection. They use the observed contrasts as a starting point, but do not document the original design rationale. This distinction is central when using trial results to think about future study planning: planning estimates are conditional illustrations, not evidence that the completed study had a particular probability of success.

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 trial enrolled 36 participants, and the primary endpoint summaries include groups of 10, 13, and 13. These small groups limit precision, as reflected by the broad confidence intervals. The posted summaries do not include individual-level observations, so the distribution of measurements and the influence of individual values cannot be examined from the registry record.

Treatment was administered for two days, and the primary endpoint was measured at 24 hours. The registry record does not report longer-term follow-up results. The findings therefore describe a brief exposure and measurement period, rather than longer-term patterns.

The registry record does not report detailed eligibility criteria, participant characteristics, adherence information, missing-data methods, or analysis populations. It also does not report the original sample-size justification, a detailed statistical analysis plan, or a multiplicity strategy. These omissions constrain assessment of how the posted results relate to the planned analysis and how broadly they apply.

Although several secondary outcomes are named, numerical results are not reported in the registry record for all of them. The registry record also does not report symptom outcomes or genetic findings. Finally, the adverse-event summary provides counts but limited detail on event types, timing, and duration; death counts are not reported in the registry record. These limitations define the scope of interpretation rather than resolving the uncertainty in the observed comparisons.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effect of Cannabinoid Agonist on Gastrointestinal and Colonic Motor Functions in Patients With Irritable Bowel Syndrome (IBS) — NCT01253408.
• Registry record last updated 2013-05-07; status last verified 2013-03.
• Results first posted 2013-05-07.
• 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.

22. Record Summary

The registry record describes a completed, randomized, double-masked, parallel-group phase 2 study sponsored by Mayo Clinic, with enrollment of 36. Participants with a history of D-IBS were assigned to dronabinol 2.5 mg twice daily, dronabinol 5 mg twice daily, or placebo for two days.

The primary endpoint was colonic transit geometric center at 24 hours. The mean values were 3.12, 3.05, and 2.77 in the 2.5 mg, 5 mg, and placebo groups, respectively. The unadjusted comparisons with placebo had confidence intervals that included zero.

The record lists five secondary outcomes and provides numerical summaries for three secondary measures. It reports no serious adverse events among participants at risk in the three groups; deaths and detailed original analysis methods are not reported in the registry record.