Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis (NCT04245709), a na phase 2 study. The primary outcome is Number of Participants With Serious Adverse Events as Measured by Patient Reporting.

2. Clinical Question

The registry describes two related aims: assessing the safety and tolerability of clenbuterol, and assessing motor function in people with ALS. The primary endpoint is a participant count for serious adverse events, measured by patient reporting. Motor function is represented among the secondary outcomes by change in ALSFRS-R, the ALS Functional Rating Scale Revised. A further secondary outcome concerns FVC decline in a per-protocol comparison.

These aims should be distinguished when interpreting the record. The primary endpoint addresses safety, not motor-function benefit. Although the registry lists motor-function outcomes, it does not report their numerical results or an estimated treatment effect. A single-group study also cannot provide a direct comparison with an untreated or alternative-treatment group. The record can therefore describe reported events in the study group, but it does not establish what would have happened to similar participants under a different treatment or no study drug.

3. Trial Design

The registry identifies this as a phase 2, single-group, open-label pilot trial of clenbuterol in people with ALS. Enrollment is listed as 25. Allocation is recorded as not applicable, and masking is listed as none. There is no concurrent control arm in the described design, so the study is not a randomized comparison.

Participants in the open-label arm were to take clenbuterol orally at 40-80 micrograms twice daily for 24 weeks. The brief study description says participants would be in the study approximately 24 weeks and would take the drug twice a day. The listed study procedures include medical history, vital signs, physical examination, blood tests, heart and lung function tests, muscle function testing, ALSFRS-R, thyroid function testing, and pregnancy tests for women who can become pregnant.

The registry lists the study as completed. Its start date is 2020-02-10, and its primary completion date is 2021-03-10. The sponsor is Dwight Koeberl, M.D., Ph.D. These record details describe the registered design and timeline; they do not establish that every participant received the same exposure or completed every assessment. Individual exposure, adherence, and assessment-completion details are not reported in the registry record.

The open-label design means treatment assignment was not masked. Without a control group, changes observed during follow-up cannot be separated from changes that might occur over time for other reasons. These design features are particularly important when considering motor-function outcomes, for which the registry does not report numerical results.

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: Intention to treat analyses were performed for 20 participants who had at least one ALSFRS-R measurement post-treatment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The baseline analysis population was determined as follows: Intention to treat analyses were performed for 20 participants (of 25 enrolled) who had at least one ALSFRS-R measurement post-treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Adverse Events as Measured by Patient Reporting, measured over Up to 24 weeks.

The primary endpoint is the number of participants with serious adverse events, measured by patient reporting, over a timeframe of up to 24 weeks. The registry description says safety at 80 mcg twice daily was the primary endpoint and that adverse events and serious adverse events would be systematically gathered as the dose increased. The endpoint is therefore a count of people who experienced a serious adverse event, rather than a measure of motor function or a comparison of treatment effects.

Participant counts are useful for describing how many people in the study group were recorded as having an event. They do not, by themselves, describe the number of separate events each person experienced, how long each person was exposed, or whether the event was caused by the study drug. The registry lists two participants with serious adverse events in the open-label arm. It also lists zero deaths.

As a general statistical point, safety monitoring can identify events that warrant careful description even when a study is not designed to estimate a comparative risk. With no concurrent comparator, the endpoint describes events recorded in this group; it does not estimate how the event count would differ under another treatment or no study drug. The registry record does not report further details about event adjudication or causal attribution.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate? A single-group trial observes participants receiving the study intervention but has no concurrent comparison group. It can describe outcomes among those participants. It cannot directly estimate a between-group treatment effect because there is no second group observed under the same study conditions. In this trial, allocation is listed as not applicable, masking as none, and the model as single group. The design is also described as open label.

As a general statistical principle, a change observed during follow-up may reflect several influences, including the intervention, the natural course of the condition, other care, or measurement variation. A control group can help separate these explanations when the groups are sufficiently comparable. Without one, an observed change cannot be attributed to clenbuterol on the basis of the design alone. Numerical motor-function results are not reported in the registry record in any case.

What does a participant count tell the reader?

The primary endpoint is a count of participants with serious adverse events. A count answers how many people were recorded as having at least one qualifying event under the registry’s endpoint definition. It is different from a count of all event episodes: one person may experience more than one event, while a participant count counts that person once for the endpoint. The registry’s serious adverse event result lists two participants; the record does not report the number of separate serious-event episodes.

Counts also differ from rates. A rate accounts for exposure time, while a simple participant count does not. Although the registry gives a timeframe of up to 24 weeks, it does not report person-time or a time-adjusted event rate. General statistical context: confidence intervals can communicate the range of values compatible with observed data under a specified method. No confidence interval for the serious-event count is reported in the registry record, so the precision of an interval estimate cannot be described.

How should the listed event percentages be read?

The serious-event terms Near-drowning accident and Pulmonary emboli are each listed with 4.0%. These are registry entries for event terms and should not be interpreted as evidence of causation. The record does not state in the registry entries how terms were selected, whether events were independently adjudicated, or how attribution to the study drug was determined. A percentage attached to a term is not the same measure as the primary endpoint’s count of participants with any serious adverse event.

More generally, safety summaries need clear definitions: which events qualify, how they are collected, how repeated events are handled, and what follow-up period is covered. The registry states that adverse events and serious adverse events were systematically gathered as the dose increased, but further collection and classification procedures are not reported in the registry record.

What do the analysis population and outcome list imply?

The registry says intention-to-treat analyses were performed for 20 participants who had at least one post-treatment ALSFRS-R measurement. This identifies a population used for those analyses, but it does not supply the analysis method or outcome estimate. The safety arm lists 25 at risk. Different outcomes can have different analysis populations, so the ALSFRS-R population should not be substituted for the safety denominator without additional information.

The registry lists three outcome measures and zero analyses. It identifies change in ALSFRS-R and FVC decline, per-protocol comparison, as secondary outcomes. The numerical results and inferential methods for these outcomes are not reported in the registry record. Details such as handling of incomplete measurements, model specification, covariate adjustment, or confidence-interval construction are also not reported.

What is the role of the planning assumptions?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. It also states that time-to-event calculations use a total number of events, while other calculations use participants per arm. These are assumptions for hypothetical planning calculations, not the design of this single-group trial. The numerical planning outputs are not reported in the registry record. Such calculations are planning illustrations, not observed power, and they do not supply evidence of an effect in this trial.

General statistical context: the choice of outcome model should reflect the type of outcome and its distribution. Counts of participants with an event are categorical summaries; repeated or time-dependent outcomes may require different methods. Over-dispersion matters in count models when variability exceeds what a simple model assumes, because ignoring it can make uncertainty estimates too narrow. The registry record does not report a model for the primary endpoint, so no specific modeling choice can be attributed to this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Open Label Arm")
n      <- c(20)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Open Label Arm  20  2  10.0  1.2  31.7  2.8  30.1  3.0  30.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: a primary serious adverse event count, change in ALSFRS-R, and FVC decline in a per-protocol comparison. Considering multiple outcomes can raise a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently notable finding can increase. Statistical approaches may address this through a prespecified hierarchy or adjustment, but the registry record does not report whether such a plan was used.

The registry lists zero analyses. Numerical efficacy results, hypothesis tests, confidence intervals, and any multiplicity adjustment are not reported in the registry record. The record also does not report an interim-analysis plan or a detailed statistical analysis plan. No inference about whether analyses were planned, conducted, or omitted should be made beyond what the record states.

For the ALSFRS-R analysis, the registry says intention-to-treat analyses were performed for 20 participants who had at least one post-treatment measurement. This criterion describes the stated population but does not explain how participants without such a measurement were handled, why measurements might be unavailable, or how missing values were treated. Those missing-data methods are not reported in the registry record. The record likewise does not report the completeness of each other outcome.

Missing data can affect both the number of observations used and the conclusions drawn, particularly if the likelihood of a missing measurement is related to health status or treatment experience. General statistical practice is to state the amount and pattern of missingness and the assumptions or methods used to address it. Those details are not reported. The reported safety count and the stated ALSFRS-R analysis population also have different listed denominators, so each should be interpreted in relation to its own outcome rather than treated as interchangeable.

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: near-drowning accident (4.0%), pulmonary emboli (4.0%).

The open-label arm lists 25 participants at risk for serious adverse events and two participants affected. The registry lists 25 participants at risk for other adverse events and 25 affected. It records zero deaths. The serious-event terms Near-drowning accident and Pulmonary emboli are each listed as 4.0%.

These figures describe what the registry records for this study group; they are not a comparison with another treatment or with no study drug. The participant count for serious events is not necessarily a count of separate event episodes. The term-specific percentages are reported separately and should not be added to or treated as a substitute for the overall serious adverse event count.

The endpoint timeframe is up to 24 weeks, and the description says events were gathered as the dose increased. The record does not give further information about event timing, duration, causal attribution, or adjudication. A serious adverse event occurring during a study does not, by itself, show that the study drug caused it. Conversely, a count observed in a small single-group study cannot determine how often such events would occur in a different population or under another treatment.

General statistical context: counts are most informative when interpreted alongside clear definitions, follow-up completeness, and uncertainty estimates. A confidence interval for the reported count is not included in the registry record.

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

The results described in the registry support a limited, descriptive reading of safety events in an open-label group. The arm lists two participants with serious adverse events, 25 with other adverse events, and zero deaths. The registry also lists two serious-event terms, each with a reported percentage. These observations summarize the record for this study; they do not establish whether an event was caused by clenbuterol.

The study’s primary question was safety, with events gathered as the dose increased over a timeframe of up to 24 weeks. The registry also aimed to assess motor function and lists ALSFRS-R change and FVC decline among the secondary outcomes. However, numerical estimates for those outcomes are not reported in the registry record. The listed outcome names alone do not indicate the direction, size, or precision of any change.

The single-group, open-label design is central to interpretation. Without a concurrent comparator, event counts cannot be compared with an alternative-treatment group, and changes in motor function cannot be distinguished from other changes over time. The record therefore does not establish comparative safety or efficacy. This is a statement about what the design and reported results can establish, not a medical recommendation.

The record identifies an ALSFRS-R analysis population of 20 participants with at least one post-treatment measurement, while the safety arm lists 25 participants at risk. It does not provide enough detail to determine how missing outcome measurements were handled or to assess whether the analyzed participants differed from those without a post-treatment measurement. That uncertainty further limits interpretation of the motor-function outcomes.

In short, the registry provides descriptive safety counts for the study group, but does not provide inferential results or numerical motor-function findings. The posted data do not support conclusions about treatment effects relative to a comparator, and they do not quantify the uncertainty around an estimated treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and outcome definition constrain interpretation. Its stated primary endpoint is a participant count for serious adverse events, while its other listed outcomes concern ALSFRS-R change and FVC decline. These answer different questions: a safety count describes recorded events, while a motor-function outcome would require a reported estimate of change and its uncertainty to assess the observed pattern.

The single-group, open-label design makes the distinction between description and comparison especially important. Counts can be reported for the treated group, but without a concurrent comparator they do not estimate a difference between treatment strategies. The same limitation applies to interpreting changes over time. This remains true even when a study has a clearly stated duration and outcome measures.

The record also illustrates why analysis populations should be read outcome by outcome. It lists 25 participants at risk for safety events and describes intention-to-treat analyses for 20 participants with at least one post-treatment ALSFRS-R measurement. Those figures refer to different stated contexts. Without further missing-data and analysis details, they should not be collapsed into a single population description.

Finally, the registry lists secondary outcome names but no analyses, and numerical motor-function results are not reported in the registry record. That absence limits quantitative assessment; it does not establish that the outcomes were unchanged. Clear reporting of estimates, uncertainty, analysis populations, and missing-data methods is important for readers to judge what a study can support. Here, the available record supports a description of safety counts, not a comparative treatment-effect conclusion.

15. Limitations

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

The central limitation is the single-group, open-label design. There is no concurrent control arm, allocation is listed as not applicable, and masking is listed as none. The resulting safety counts are descriptive, and any change over time cannot be separated from other influences using this design alone.

The registry reports the primary safety count but does not report numerical results for the listed secondary outcomes, including ALSFRS-R change and FVC decline. It also lists zero analyses. Consequently, the size and precision of any motor-function change cannot be evaluated from the registry record. Confidence intervals and hypothesis tests for these outcomes are not reported.

The listed analysis population for ALSFRS-R comprises 20 participants with at least one post-treatment measurement, whereas the safety arm lists 25 participants at risk. The record does not explain missingness, give outcome-specific completion details, or report methods for handling missing data. It also does not report event-level timing, adjudication, or causal attribution for the serious adverse events.

Further limitations include the absence of a reported detailed statistical analysis plan, multiplicity approach, and interim-analysis information. Details of adherence and individual exposure are not reported in the registry record. The record describes a dose range and twice-daily administration but does not provide participant-level dosing information. These limitations restrict what can be inferred from the registered results; they do not establish that unreported analyses or procedures did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clenbuterol on Motor Function in Individuals With Amyotrophic Lateral Sclerosis — NCT04245709.
• Registry record last updated 2022-09-06; status last verified 2022-08.
• Results first posted 2022-09-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed phase 2, open-label, single-group pilot trial of oral clenbuterol in people with ALS. Enrollment is listed as 25, with twice-daily dosing of 40-80 micrograms for 24 weeks. The primary endpoint is the number of participants with serious adverse events, measured by patient reporting, over up to 24 weeks.

The open-label arm lists two participants with serious adverse events, 25 with other adverse events, and zero deaths. Near-drowning accident and Pulmonary emboli are each listed as serious-event terms with 4.0%. The registry also lists change in ALSFRS-R and FVC decline as secondary outcomes, but numerical results for these outcomes are not reported in the registry record.

The design has no concurrent comparator, and the record does not report detailed analysis methods, missing-data handling, or uncertainty estimates. The safety counts are therefore descriptive and do not establish comparative effects or causation.