Is Topical CBD Effective in Treating Thumb Joint Arthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Is Topical CBD Effective in Treating Thumb Joint Arthritis (NCT04611347), a randomized phase 2 study. The primary outcome is Change in Hand Strength During Intervention and at Follow-up..

2. Clinical Question

The registry record describes the study hypothesis as CBD being more effective than placebo for relieving pain and improving patient-reported outcomes. However, the posted primary outcome is grip strength, not a direct measure of pain or a patient-reported outcome. The record lists a side-effect outcome as secondary, but does not report a posted result for pain relief or patient-reported outcomes in the information available in the registry record.

The comparison should be understood within the crossover structure: participants received both conditions in sequence, rather than remaining in one treatment group throughout. The record does not report how the treatment sequence, period, or any possible carryover effect was handled in the primary statistical analysis. The result therefore describes the posted grip-strength contrast; details needed to connect that contrast to a fully specified crossover analysis are not reported in the registry record.

3. Trial Design

This was a randomized, quadruple-masked, phase 2 trial with a crossover model. The registry record lists University of Virginia as the sponsor and gives the study status as completed. The recorded start date is 2020-07-28, and the primary completion date is 2021-01-21. Enrollment is listed as 18.

In the described design, participants were randomly assigned to start with CBD or Shea butter. They received the assigned condition for 2 weeks, then crossed over to the other condition for 2 additional weeks. The record describes treatment as blinded to subjects and investigators. It says the cream was applied at the thumb base twice daily for 1 hour. The control was Shea butter alone.

A crossover design allows each participant to receive both conditions, so comparisons can account for stable differences between individuals when the analysis is designed appropriately. It also makes treatment sequence and period relevant: outcomes can potentially vary over time, and an effect of one condition could persist into the next period. Whether the study used a washout interval, and how it addressed period or carryover effects, are not reported in the registry record.

The primary outcome is described as change in hand strength during intervention and at follow-up, with a timeframe of change from baseline to 2 weeks. The registry record gives grip strength in kilograms as the measure. It says 18 people completed each intervention and served as their own control. The results list a mean for each intervention, but the record does not fully describe the statistical model, the timing and handling of the crossover measurements, or the analysis population. The original protocol details and the trial's own sample-size justification 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

Analysis population for the primary outcome, as defined in the registry: Subjects served as their own control so 18 people completed each intervention.

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 Change in Hand Strength During Intervention and at Follow-up., measured over Change from baseline to 2 weeks.

The primary endpoint is described as change in hand strength during intervention and at follow-up. The measure is grip strength in kilograms, and the stated timeframe is change from baseline to 2 weeks. Grip strength is a continuous measure: it can take a range of numeric values rather than placing participants into categories. Reporting a mean gives a compact description of the measured strength in each condition, while a measure of spread indicates how variable the observations are.

Grip strength can be used as a functional measure in a study of hand and thumb arthritis. It reflects the force measured during a grip task, rather than directly measuring pain or a participant's overall view of symptoms. The registry record's stated hypothesis mentions pain relief and patient-reported outcomes, but the posted primary endpoint is grip strength. That distinction matters when interpreting what the reported outcome can address.

The posted means are 24.0 for CBD and 23.0 for Shea butter, in kilograms. The reported comparison is a mean difference, with a confidence interval. The registry record does not explain how the change-from-baseline endpoint was converted into the posted group values or how repeated measurements from the crossover periods contributed to those values. These analysis details are not reported in the registry record, so the means should be read as the posted summary rather than as a complete account of the endpoint definition and analysis.

7. Results Posted in the Registry

• Shea Butter Group: mean 23.00 versus 24.00 on control; difference -1.00 (95% CI -2.67 to 0.67), standardized effect d = -0.39; z-test p = 0.242.

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish the observed values from the uncertainty around them. The registry result reports a mean for each condition, a mean difference, standard deviations, a confidence interval, and an unadjusted p-value. These quantities address related but different questions: the means describe the measurements, the difference describes their contrast, and the interval and p-value characterize uncertainty under a statistical model.

What does a mean describe?

General explanation: a mean is the arithmetic average of observations. It provides a single summary of the location of a continuous measure, but does not describe how individual measurements are distributed. In this trial, the reported means are 24.0 for CBD and 23.0 for Shea butter, and grip strength is measured in kilograms. The associated standard deviations, 2.3 and 2.8, describe the spread of measurements around their respective means. A standard deviation is not the uncertainty in the difference between means.

What does the mean difference represent?

The posted mean difference is -1.0 kg, with the group means also stated as 24.0 for CBD and 23.0 for Shea butter. The sign indicates the direction of the contrast as encoded in the registry result. A difference in means is expressed in the measurement's original units, which makes its scale directly interpretable as a grip-strength contrast. The registry record does not explain the precise calculation convention or give a full analysis specification.

General explanation: in a crossover trial, each participant receives both conditions. A paired analysis can use the within-person difference, which may account for stable participant characteristics shared across periods. A crossover analysis may also need to account for treatment sequence and period, and to consider whether effects persist between conditions. The registry record says participants served as their own control, but the primary analysis method and its handling of these features are not reported in the registry record. It is therefore not possible to confirm from the posted summary how the crossover structure entered the calculation of the interval or p-value.

Why is a confidence interval useful?

General explanation: a confidence interval expresses uncertainty about an estimated quantity, under a specified statistical procedure. It gives a range of values that remain compatible with the data and method. The reported interval for the mean difference runs from -2.674 to 0.674 kg. Since zero falls inside that range, the interval does not distinguish the observed contrast from no difference at its stated confidence level. The confidence level and the method used to construct the interval are not reported in the registry record.

What does the p-value add?

The unadjusted p-value is 0.242. General explanation: a p-value evaluates how well the data align with a null model, conditional on the model and its assumptions. It is not a measure of the magnitude of a result, and it does not give the chance that the null model is true. The label unadjusted indicates that the value is reported without an adjustment for multiple comparisons. Whether other analyses were planned or how multiplicity was handled is not reported in the registry record.

The result also lists a pooled standard deviation of 2.562 and a standardized difference of -0.390. General explanation: standardizing a difference expresses it relative to a measure of variability, allowing comparisons across measures with different units. Such a standardized summary does not replace the difference in kilograms, and its interpretation depends on how the variability measure was chosen. The record does not describe a clinical threshold for interpreting this standardized value.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model expects. It can make uncertainty estimates too small if the model does not accommodate the extra variation. That concern is especially relevant to outcomes modeled as counts or event rates. The posted primary outcome is continuous grip strength, and the registry record does not report an over-dispersion assessment or a model requiring one. No conclusion about over-dispersion can be drawn from the posted summary.

The results list 18 participants for each intervention and state that 18 people completed each intervention while serving as their own control. These descriptions do not establish that every analysis used all such observations or explain how missing measurements, if any, were handled. The analysis population and missing-data approach are not reported in the registry record. The number of posted analyses is recorded as 0, while a primary outcome summary and comparison are listed; the record does not explain this distinction. Overall, the summaries support a descriptive reading of the contrast, but do not provide enough information to reconstruct the trial's statistical analysis.

10. Confidence Intervals and Precision

The reported mean difference in grip strength is -1.0 kg, with a confidence interval from -2.674 to 0.674. The interval includes zero and extends to values on either side of it. Thus, the posted data are compatible with no mean difference, as well as with a contrast in either direction within the interval. The estimate should not be read as precise evidence of a particular difference.

General explanation: a confidence interval reflects uncertainty about an estimated quantity under the statistical method used. A narrower interval indicates more precision, while a wider interval indicates less precision. The interval's width is shaped by the amount and variability of the data and by the analysis method. In a crossover study, accounting for the paired measurements may affect the uncertainty; the registry record does not report whether or how such pairing was incorporated.

The record does not state the confidence level or the method used to calculate the interval. It also does not report a clinical threshold that would indicate which differences in grip strength matter to patients. Consequently, the interval can be described statistically, but its clinical importance cannot be determined from the posted information alone.

The reported standard deviations are 2.3 for CBD and 2.8 for Shea butter. They describe variability in the condition-specific measurements, not the precision of the mean difference. The confidence interval is the more direct summary of uncertainty for that contrast. Its span, together with the unadjusted p-value of 0.242, indicates that the registry result does not precisely isolate the magnitude or direction of a difference.

11. 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 participants per arm, not total events. They are planning illustrations based on the observed effect, not the original trial's design justification. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original sample-size assumptions used to design this trial are not reported in the registry record.

For planning for 100% of the observed effect, the illustration gives 104 participants per arm for 80% power and 138 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 184 participants per arm for 80% power and 246 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 413 participants per arm for 80% power and 552 participants per arm for 90% power.

In general, power is the chance that a study will detect an effect of a specified size under the planning assumptions, if that effect is present. The 80% and 90% columns indicate different target probabilities of detecting the chosen effect. Requiring the higher target generally entails a larger planned sample. Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm when the assumed effect is a smaller fraction of the observed effect.

These are planning illustrations, not observed power. They use a two-arm equal-allocation normal approximation, whereas the trial is described as a crossover study in which participants served as their own control. The figures do not account for any crossover-specific design features beyond the stated assumptions, and should not be read as a reconstruction of the trial's original sample-size plan.

12. 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 = -1.000; pooled standard deviation σ = 2.562.
2. n = 2 × (1.96 + 0.842)² × 2.562² / -1.000² = 103.1, rounded up to 104 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 <- -1                      # observed difference in means
sigma <- 2.56222559506379                     # 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(4611347)
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 = 104 (80% power), 138 (90% power)
 75% of observed effect: n per arm = 184 (80% power), 246 (90% power)
 50% of observed effect: n per arm = 413 (80% power), 552 (90% power)
power.t.test: 104 
Simulated power at n = 104 per arm: 0.801 (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.

13. Multiplicity, Missing Data and Analysis Populations

The primary outcome is change in hand strength, described as grip strength in kilograms. The registry record also lists a secondary outcome concerning the rate of side effects using the novel CBD cream, and reports five outcome measures. The number of analyses is recorded as 0, while the result information includes a primary summary and comparison. The record does not explain this discrepancy or identify a complete set of analyses.

Multiplicity arises when multiple outcomes, time points, or statistical comparisons are examined. General explanation: if many statistical tests are conducted, the chance of at least one result appearing unusual by chance can increase. Adjustments or a prespecified hierarchy can address this issue, but the registry record does not report a multiplicity strategy. The primary comparison's p-value is explicitly unadjusted. It should not be interpreted as if a correction for other outcomes or comparisons had been applied.

The record specifies a change-from-baseline-to-2-weeks timeframe for the primary endpoint and refers to intervention and follow-up. It does not provide a full analysis plan describing how the measurement occasions were selected or whether other time points were analyzed. The protocol's analysis plan, interim analyses, and any prespecified outcome hierarchy are not reported in the registry record.

The registry describes the study as a crossover trial and says participants served as their own controls. However, it does not report the analysis population definition or how the primary analysis handled participants who did not complete measurements, if any. A missing-data method, reasons for missingness, and sensitivity analyses are not reported in the registry record. No assumption about complete follow-up or missingness should be inferred from the intervention-specific participant counts alone.

These omissions limit assessment of how the posted p-value and confidence interval relate to the full set of planned outcomes and analysis choices. They also mean the crossover-specific treatment of periods, sequence, and possible carryover cannot be verified. The registry record does not report an interim-analysis plan, the original statistical analysis plan, or a detailed account of how analysis populations were defined.

14. 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 serious adverse-event figures list 18 participants at risk during the CBD intervention and 18 during the Shea Butter intervention. The reported number affected by a serious adverse event is 0 for each condition. Deaths are reported as 0 for each condition. The figures for other adverse events also list 18 at risk and 0 affected for each intervention.

These entries describe the events recorded in the registry record; they do not establish that no adverse effects of any kind occurred. The registry separately lists a secondary outcome concerning the rate of side effects using the novel CBD cream, but a detailed result for that outcome is not reported in the registry record.

General explanation: safety counts are most informative when interpreted alongside the definitions of events, the observation period, completeness of reporting, and the number of people followed. The record does not provide detailed event definitions or further context for these counts. The intervention-specific figures should not be added together, particularly in a crossover design where participants may receive both conditions. The counts also do not provide a comparative statistical analysis of safety.

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

The posted primary result is a comparison of grip-strength means for CBD and Shea butter. The means are 24.0 and 23.0 kg, respectively, with a reported mean difference of -1.0 kg. The confidence interval, from -2.674 to 0.674, includes zero, and the unadjusted p-value is 0.242. These statistics describe an uncertain contrast; they do not establish a clear difference between the conditions.

The result does not directly answer every question stated in the registry's rationale and hypothesis. Those statements concern pain relief and patient-reported outcomes, while the posted primary outcome is grip strength. A grip-strength result cannot by itself establish an effect on pain or broader patient-reported outcomes. The registry record does not provide posted results for those outcomes in the information available.

The crossover structure is important to interpretation. Participants were described as receiving both interventions, which can support within-person comparisons, but the analysis method for the repeated measurements is not reported. The record does not state how treatment sequence, period, or possible carryover effects were addressed. The posted group summaries therefore do not reveal the full details needed to assess a crossover analysis.

The result is also not a complete assessment of the balance of benefits and harms. Serious and other adverse-event counts are listed as zero affected in each intervention group, but the record does not give detailed side-effect results or full context for event ascertainment. The listed adverse-event figures are not a substitute for a comprehensive safety analysis.

In general, statistical uncertainty and clinical importance are separate considerations. The confidence interval describes uncertainty in the mean difference under the method used, while a clinical interpretation would also require a meaningful threshold and relevant patient outcomes. Such a threshold is not reported in the registry record. The appropriate reading is limited: the posted grip-strength comparison is imprecise, and the available information does not establish an effect on pain, patient-reported outcomes, or overall clinical benefit.

16. Why This Trial Matters Statistically

This trial is statistically instructive because its crossover design changes how the comparison should be understood. Each participant served as their own control, and the record describes a sequence in which participants received both CBD and Shea butter. In general, this can reduce the influence of stable differences between people, but it also makes the analysis of paired measurements, treatment periods, sequence, and possible carryover important. The registry record does not report how those features were handled statistically.

The posted result illustrates the distinction between an estimate and its uncertainty. The mean difference is -1.0 kg, but its confidence interval extends from -2.674 to 0.674 and includes zero. The p-value is 0.242 and is unadjusted. Neither the point estimate nor the p-value alone captures all the information in the result; the interval shows that a range of contrasts remains compatible with the analysis.

The endpoint also matters. The stated study rationale refers to pain and patient-reported outcomes, while the posted primary outcome is grip strength in kilograms. The measure is useful as a functional outcome, but it does not directly stand in for pain or a participant's overall symptom experience. Matching the statistical outcome to the clinical question is essential when interpreting a trial.

Finally, the sample-size illustrations are based on a two-arm planning approximation, while the actual study is described as crossover. Recognizing this difference prevents planning figures from being mistaken for the trial's own design assumptions. Together, these features show why statistical interpretation requires attention to design, endpoint, uncertainty, and reporting completeness, not only to a single test result.

17. 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 registry record gives a limited account of the statistical analysis. It does not report the original sample-size justification, a full analysis plan, or the method used to calculate the confidence interval and p-value. The confidence level for the interval is also not stated. The sample-size illustrations use a two-arm equal-allocation normal approximation, which is not the crossover design described for the trial.

Important crossover details are not reported in the registry record. These include whether a washout interval was used, how treatment sequence and period were handled, and whether possible carryover was assessed. The posted result does not explain how the within-participant measurements contributed to the reported group means and contrast. This limits evaluation of whether the analysis reflects the design.

The primary endpoint description refers to change from baseline to 2 weeks and to intervention and follow-up, but the results do not fully explain the measurement schedule or how the reported means correspond to that endpoint. The record does not state the analysis population, how incomplete observations were handled, or whether sensitivity analyses were performed.

Multiplicity procedures are not reported, and the primary p-value is unadjusted. Although the record lists a secondary side-effect outcome and five outcome measures, it does not provide a complete account of the planned outcome analyses. The posted information also does not include results for pain relief or patient-reported outcomes, despite their presence in the study hypothesis. These limitations constrain the conclusions to the reported grip-strength summary and the listed adverse-event counts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Is Topical CBD Effective in Treating Thumb Joint Arthritis — NCT04611347.
• Registry record last updated 2025-07-03; status last verified 2025-06.
• Results first posted 2025-07-03.
• 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.

21. Record Summary

The registry record describes a completed, randomized, quadruple-masked, phase 2 crossover trial sponsored by University of Virginia. The study compared topical CBD cream with Shea butter for thumb basal joint arthritis. Participants were assigned to a treatment sequence, received each condition for 2 weeks, and served as their own controls.

The primary outcome was change in hand strength, measured as grip strength in kilograms, with a stated timeframe of change from baseline to 2 weeks. The posted means were 24.0 for CBD and 23.0 for Shea butter. The reported mean difference was -1.0 kg, with a confidence interval from -2.674 to 0.674 and an unadjusted p-value of 0.242.

The confidence interval includes zero, and the registry record does not report the full crossover analysis method, original sample-size justification, missing-data approach, or multiplicity plan. Serious and other adverse-event counts are listed as 0 affected for each intervention. Interpretation is limited to these posted results and record details.