Cannabis for Spasticity in Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cannabis for Spasticity in Multiple Sclerosis (NCT00682929), a randomized phase 1, phase 2 study. The primary outcome is Change From Week 0 to Week 3 in the Rate of Torque Increase, Flexion.

2. Clinical Question

The clinical question was whether the two cannabinoid approaches were associated with changes in spasticity-related measures over the study period. The stated study purpose included learning whether inhaled cannabis and oral cannabinoid were safe and effective in reducing spasticity and tremor symptoms. The primary outcome focused on a laboratory measure of resistance to passive knee movement rather than a direct report of tremor or a broad measure of daily functioning.

The posted primary outcome summaries contain results for each of the three arms, but there is no reported primary two-arm comparison estimate. The available numbers therefore describe arm-level changes; they do not by themselves establish the size or precision of a treatment-versus-placebo effect. The registry record does not report a formal primary outcome analysis or a rationale for the study’s sample size.

3. Trial Design

This was a randomized, double-masked, parallel study listed in phase 1 and phase 2. The sponsor was the University of California, Davis. Enrollment was 41. The study began on 2004-04-14, and primary completion was recorded as 2011-08-17. Its status is terminated. The registry record does not state why the study was terminated.

The arms combined active and placebo preparations by route. The inhaled cannabis arm was described as comparing inhaled cannabis with oral placebo. The oral THC arm was described as comparing inhaled placebo with oral THC. The placebo arm received inhaled placebo and oral placebo. Thus, each active approach had a placebo counterpart by the other route, while the third arm received placebo by both routes. Further details about the randomization procedure, sequence generation, allocation concealment, masking procedures, treatment duration, or adherence are not reported in the registry record.

The primary outcome was assessed from Week 0 to Week 3. The registry also lists secondary measures at Week 3 and Week 7, including spasticity, ambulation, walking time, hand dexterity, and cognitive test performance. The primary outcome description says only 28 subjects completed the study through the Week 7 visit. Two subjects who discontinued early, one for an adverse event and one who withdrew, were active at the Week 3 visit and were included in the Week 3 analysis. Only 25 total subjects had Lido assessments at both Week 0 and Week 3.

Although enrollment was 41, the posted outcome results use smaller outcome-specific groups. The registry record does not provide a complete participant flow, reasons for all missing assessments, or a stated analysis population. These limits matter when interpreting the arm summaries and the applicability of any 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only 28 subjects completed the study through the Wk 7 visit; 2 subjects who discontinued early (AE and withdraw by subject) were active at the Wk 3 visit and were included in the Wk 3 analysis; only 25 total subjects had Lido assessments at both the Week 0 and Week 3 study visits and were able to be analyzed for this outcome measure.

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 From Week 0 to Week 3 in the Rate of Torque Increase, Flexion, measured over Week 0, Week 3.

The primary endpoint was change from Week 0 to Week 3 in the rate of torque increase during flexion, measured in degrees/second. A modified servo-controlled torque motor system was used to assess resistance during passive knee movement. The description says the system measured the torque required to move the knee joint without voluntary resistance at both high and slow velocities.

In the endpoint description, slow displacement torque represents passive resistance from connective tissue and non-contracting muscle. Rapid displacement torque includes passive resistance and active involuntary resistance. The active component is attributed to the stretch reflex and is described as correlating with clinical assessment of spasticity. This makes the rapid torque measure a physiologic proxy related to spasticity, rather than a direct symptom rating.

The change was calculated as the Week 3 value minus the Week 0 value. Accordingly, a negative result represents a decrease in measured torque; the registry describes this direction as correlating with decreased spasticity and a better outcome. That direction is important because a negative change is not a worsening simply because its numerical sign is negative. The endpoint description does not report the minimum change considered clinically meaningful, nor does the registry record explain how this measure was validated for the specific treatment comparison.

The primary summaries report means and standard deviations for the arm-level change scores. The number of participants with measurements differs from the enrollment, and only 25 total participants had assessments at both visits. No primary confidence interval or formal treatment-versus-placebo estimate is reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical change score, reported as a mean with a standard deviation. A mean describes the average change among participants with observed assessments in an arm. A standard deviation describes how dispersed those individual changes were around that arm’s mean. It is not a confidence interval for the treatment effect, and it does not directly indicate whether two arms differ.

What a randomized comparison would estimate

General statistical explanation: a treatment comparison usually estimates the difference between outcomes in the randomized groups, with uncertainty represented by a confidence interval and often a test statistic or p-value. A confidence interval gives a range of values compatible with the data and the analysis assumptions; its width conveys precision. For this trial’s primary outcome, the registry reports arm-level means and standard deviations but does not report the corresponding between-arm estimate or confidence interval. No primary p-value is reported. The posted summaries therefore support descriptive reading, not a complete inferential comparison.

The primary endpoint’s sign convention also matters. The score is Week 3 minus Week 0, so a negative value indicates a decrease in torque. The registry states that this decrease correlates with decreased spasticity and a better outcome. This is a description of how to interpret the measure, not evidence that any observed arm-level change is caused by treatment. A change within an arm can reflect multiple influences, and the randomized contrast is needed to distinguish the comparative result.

Why the standard deviations matter

General statistical explanation: variability affects how precisely an average and a group difference can be estimated. Greater variability, all else equal, tends to make an estimate less precise. In a small group, the observed standard deviation itself may also be uncertain. The primary outcome groups are small, and their reported standard deviations differ. A formal comparison would need to account for the observed group sizes and variability, as well as the analysis method. The registry record does not report the primary comparison method or its uncertainty estimate.

General statistical explanation: over-dispersion occurs when outcome variability is greater than a model assumes. If a model underestimates variability, its standard errors may be too small and its intervals too narrow. The posted primary outcome is summarized with means and standard deviations; the registry record does not report a model or a dispersion assessment for the primary analysis. No claim about over-dispersion in this trial can be made from the record.

How to interpret the secondary comparisons

The posted secondary comparisons use the placebo arm as the reference and report oral THC comparisons for selected continuous outcomes. Their estimates are unadjusted mean differences with confidence intervals and unadjusted p-values. General statistical explanation: an unadjusted p-value assesses a comparison without correcting for the number of outcomes or comparisons considered. When many outcomes are examined, the chance of at least one apparently unusual result can increase. A confidence interval describes uncertainty for its particular comparison, but it does not account for testing multiple outcomes unless the analysis explicitly adjusts for multiplicity.

The record does not report a multiplicity adjustment or an analysis plan specifying which secondary outcome comparisons were confirmatory. The secondary estimates should therefore be treated cautiously, especially because many outcomes are listed and the registry reports no formal analyses. The arm-level secondary summaries and the unadjusted comparisons are distinct: the latter compare groups, while the former describe each group’s observed change.

What the sample-size illustrations mean

The posted planning illustrations are based on observed effects, not on the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and detection of a stated fraction of the observed effect. These are hypothetical planning calculations for the comparisons to which they are attached. They are not the number of participants actually analyzed, do not show the trial’s observed power, and do not establish the study’s original enrollment target or its justification. The registry does not report the trial’s original sample-size calculation.

General statistical explanation: planning an adequately sized study requires assumptions about the effect worth detecting, outcome variability, the significance level, desired power, and design features. A calculation based on an observed effect can be unstable when the original groups are small, and the observed effect may not be a reliable planning target. The posted illustrations are best interpreted as conditional examples under their stated assumptions, not as retrospective evidence that the study was adequately or inadequately powered.

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("1) Inhaled Cannabis", "2) Oral THC", "3) Placebo")
n   <- c(7, 9, 9)
m   <- c(0.0018, -0.0121, 0.0007)
sp  <- c(0.0071, 0.0183, 0.0064)
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  1) Inhaled Cannabis  7  0.002  0.007  -0.005  0.008
CARM  2) Oral THC  9  -0.012  0.018  -0.026  0.002
CARM  3) Placebo  9  0.001  0.006  -0.004  0.006

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. It lists a primary outcome and many secondary measures, but it does not state which secondary analyses were prespecified as confirmatory, whether a hierarchy was planned, or whether any adjustment was made for testing multiple outcomes. The posted secondary comparisons are identified as unadjusted. If many outcomes are examined without adjustment, isolated results can appear notable by chance; this general concern is especially relevant when the full analysis plan is unavailable.

The record also does not report a missing-data plan, imputation method, sensitivity analysis, or rule for including participants in each analysis. The primary outcome description states that only 25 total subjects had Lido assessments at both Week 0 and Week 3. It also notes that 28 completed through the Week 7 visit and that 2 subjects who discontinued early were active at Week 3 and included in its analysis. These details show that outcome availability was not the same as enrollment, but they do not explain all missing assessments or establish how missingness was handled statistically.

The analysis populations are not reported in a way that identifies, for example, an intention-to-treat population or a per-protocol population. The arm-specific observed sample sizes are available for the primary endpoint, but the registry does not describe the full participant flow from randomization through each outcome assessment. Reasons for missing data beyond the two early discontinuations described are not reported in the registry record.

No formal analyses are listed in the registry record. In particular, there is no reported primary treatment-effect estimate, inferential test, or missing-data sensitivity analysis. These omissions limit the ability to assess robustness and to distinguish planned analyses from descriptive summaries. They should be kept separate from the observed arm summaries: the summaries remain descriptive details, while the missing analysis details constrain what can be inferred from them.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypotension (7.7%), dehydration due to gastroenteritis (7.7%), hypersexual thoughts (7.7%), planned insertion of baclofen pump (7.1%).

The adverse-event results use group-specific counts of participants at risk and participants affected. For serious adverse events, the inhaled cannabis group had 3 affected among 13 at risk, the oral THC group had 1 among 14, and the placebo group had 0 among 14. Deaths were reported as 0 in each group. For other adverse events, the affected counts were 13 among 13 at risk for inhaled cannabis, 14 among 14 for oral THC, and 12 among 14 for placebo.

The registry also lists serious-event terms with percentages: hypotension, 7.7%; dehydration due to gastroenteritis, 7.7%; hypersexual thoughts, 7.7%; and planned insertion of baclofen pump, 7.1%. The record does not provide enough context in these entries to determine the relationship of each event to treatment or to infer causation from the term and percentage alone.

These figures are descriptive counts from small groups. They do not provide a precise comparative estimate of safety, and the absence of a reported event in a group does not establish that the event cannot occur. The record does not report additional context such as event timing, duration, severity grading beyond the serious classification, or investigator attribution. The counts should therefore be read as the adverse-event information recorded for this study, not as a definitive comparison of risk.

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

The posted results describe observed changes in a laboratory measure and selected secondary outcomes among participants with available measurements. The primary outcome definition gives the direction of interpretation: a negative change means a decrease in torque and is described as correlating with decreased spasticity and a better outcome. The primary arm means alone do not provide a direct estimate of how much one randomized group differed from another.

A trial result is most informative when the comparison, uncertainty, analysis population, and missing-data handling can be assessed together. For the primary outcome, the registry does not report a between-arm estimate, confidence interval, or p-value. The smaller outcome-specific groups and incomplete assessments make precision and generalizability important concerns. The available information does not establish whether the observed changes are clinically meaningful, because no threshold for meaningful change is reported.

The secondary results add observations across several domains but are unadjusted and do not amount to independent confirmation of the primary result. The registry does not report a multiplicity plan or formal analyses. Those limitations are relevant when considering any individual secondary finding or apparent pattern across measures.

The study’s stated purpose included spasticity and tremor, while the primary outcome is a torque-based measure related to spasticity. The posted primary result does not directly answer every aspect of that broader purpose. Nor does an arm-level change establish a causal treatment effect without the corresponding comparative analysis.

Accordingly, the record supports a cautious, descriptive account of the outcomes that were posted. It does not establish that either active approach is effective or ineffective, and it does not support medical recommendations. The study status is terminated, but the reason for termination is not reported in the registry record. The available information should be interpreted within these reporting limits.

14. Why This Trial Matters Statistically

This study illustrates why arm-level summaries and comparative treatment estimates answer different statistical questions. Means and standard deviations describe observed changes within randomized groups, but they do not themselves quantify the randomized contrast or its precision. In the primary outcome record, the absence of a reported comparative estimate is consequential: readers cannot assess the primary difference with a confidence interval or formal test from the posted results.

It also highlights the importance of outcome availability. Enrollment was 41, while the primary endpoint summaries include smaller groups, and the record states that only 25 total participants had the two required Lido assessments. The distinction between enrollment, follow-up completion, and analysis sample is central to judging precision and possible bias. Without a full participant flow and missing-data analysis, the influence of unavailable outcomes remains uncertain.

The study also has multiple measures across different domains and time points. This makes clear why a prespecified hierarchy or multiplicity strategy matters: without one, secondary findings are more appropriately regarded as exploratory. The posted sample-size illustrations are also different from the original design justification. They are planning scenarios based on observed effects under stated assumptions, not evidence about observed power or the rationale for the trial’s enrollment.

Finally, the endpoint itself demonstrates the value and limits of surrogate or physiologic measures. The record describes a relationship between rapid torque and clinical assessment of spasticity, but does not report a clinical-importance threshold. Measurement relevance and treatment effect are separate issues: a plausible measure does not replace an adequately reported comparison. These are useful statistical distinctions when reading small clinical trials with incomplete outcome reporting.

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.

Several trial-specific limitations affect interpretation. The study was terminated, and the registry record does not state why. Although enrollment was 41, primary outcome summaries are based on small outcome-specific groups. The record states that only 25 total subjects had Lido assessments at both Week 0 and Week 3, and only 28 completed through the Week 7 visit. The participant flow and reasons for all unavailable assessments are not reported.

The primary results are arm-level summaries without a reported primary comparison estimate, confidence interval, or p-value. As a result, the posted means cannot show the precision of the between-group effect. The record also does not report the sample-size justification, a primary analysis method, the analysis population, a missing-data strategy, or sensitivity analyses. These absences prevent assessment of several important design and analysis choices.

The registry’s outcome description says the torque measure correlates with clinical assessment of spasticity, but it does not specify a clinically meaningful change threshold. This limits interpretation of the magnitude of an observed change. The study purpose mentions tremor as well as spasticity, but the listed primary endpoint measures torque related to spasticity rather than tremor directly.

There are numerous secondary measures, and the available secondary comparisons are unadjusted. The record does not report a multiplicity plan or formal analyses. The different outcome domains and outcome-specific sample sizes make it difficult to treat the results as a single coherent pattern without a prespecified analytic framework. Finally, treatment procedures, adherence, detailed masking methods, and the reason for termination are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cannabis for Spasticity in Multiple Sclerosis — NCT00682929.
• Registry record last updated 2018-05-18; status last verified 2018-04.
• Results first posted 2018-05-18.
• 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

NCT00682929, “Cannabis for Spasticity in Multiple Sclerosis,” was sponsored by the University of California, Davis. It is listed as a randomized, double-masked, parallel phase 1 and phase 2 study, with enrollment of 41 and status terminated. The registry records a start date of 2004-04-14 and primary completion on 2011-08-17.

The primary outcome was change from Week 0 to Week 3 in the rate of torque increase during flexion. The posted primary data are arm-level means and standard deviations; a primary comparative analysis is not reported. Selected secondary outcomes and adverse-event counts are also recorded. The registry does not report the sample-size justification, a full analysis plan, multiplicity handling, missing-data methods, or the reason for termination.