An Open-Label Trial of N-Acetylcysteine in Cannabis Dependent Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Trial of N-Acetylcysteine in Cannabis Dependent Adolescents (NCT00542750), a na phase 1, phase 2 study. The primary outcome is Feasibility of Recruitment, Measured by Number of Participants Recruited and Retained During Study Period.

2. Clinical Question

The central question was about whether a trial of N-acetylcysteine could be conducted in this population, rather than whether it outperformed another treatment. The registry describes the study as a pilot and proof-of-concept feasibility preliminary study. It also says that tolerability, marijuana use, and reactivity to marijuana cues would be investigated. Those topics are not substitutes for the primary feasibility question, and the registry record does not report results for them.

The record lists enrollment as 24. That enrollment figure does not tell readers how many participants completed the study or met any specific retention criterion. Although the primary outcome is described as the number recruited and retained, the registry record does not report those counts as an outcome result. It also does not define a recruitment or retention threshold for deciding whether the study was feasible. The available information therefore identifies the question and the trial’s intended intervention, but does not establish the primary outcome’s observed result.

3. Trial Design

This was a completed, open-label, single-group trial listed as Phase 1 and Phase 2. The registry identifies N-acetylcysteine as the intervention and lists enrollment as 24. There was no masking, and the allocation field is recorded as not applicable. The record explicitly identifies the study as not being a randomized comparison. Consequently, there is no parallel control group against which to compare the participants receiving N-acetylcysteine.

All participants were to receive N-acetylcysteine 1200 mg twice daily during four weeks of participation. The study began in 2008-01, and primary completion is recorded as 2008-12. Its status is completed. Those dates describe the registry timeline, but they do not provide details about the actual recruitment schedule, follow-up contacts, or how retention was measured.

The stated purpose was to determine the feasibility of conducting a trial of N-acetylcysteine in adolescents with cannabis dependence. The record says tolerability, marijuana use, and reactivity to marijuana cues would also be investigated. It lists one outcome measure, with recruitment and retention as the primary outcome. However, it lists no analyses. The statistical analysis methods, analysis population, and any protocol-defined decision criteria are not reported in the registry record.

Because all participants received the intervention and there was no comparator, the design can describe observations among participants in the study but cannot by itself distinguish intervention effects from changes over time or other influences. Open-label means participants and study staff were not masked to the intervention. This design may be appropriate for an initial feasibility question, but it does not provide a randomized estimate of comparative treatment effects. No further design rationale or sample-size justification is 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.

Before assignment: After informed consent, an assessment/screening visit was used to determine if prospective participants met criteria for inclusion. Briefly, participants were required to be regular cannabis users meeting current criteria for dependence. Participants with unstable psychiatric or medical issues were excluded.

Overall Study

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 Feasibility of Recruitment, Measured by Number of Participants Recruited and Retained During Study Period, measured over one year.

The primary endpoint is described as feasibility of recruitment, measured by the number of participants recruited and retained during the study period. The registry gives the timeframe as one year and identifies the outcome unit as participants. This makes the endpoint a count-based measure of whether the study could enroll and keep participants involved, rather than a clinical measure of cannabis use or a comparison of treatment outcomes.

Recruitment and retention are useful feasibility measures because a study needs to enroll participants and maintain their participation in order to carry out its planned assessments. In general, these counts can help researchers judge whether a larger or longer study is practicable. To interpret them fully, readers would need the observed counts and clear definitions: for example, what counted as recruited, what counted as retained, and whether retention was assessed at a particular visit or across the study period. Those operational details and the primary outcome result are not reported in the registry record.

The record lists enrollment as 24, but it does not report the number retained as the primary endpoint result. Enrollment alone cannot establish retention, nor does it indicate whether a prespecified feasibility target was met. The registry classifies the outcome as binary and describes its count interpretation as participants with an event; it does not state a threshold or explain how that classification was applied to recruitment and retention. As a result, the endpoint’s stated purpose is clear, but its result and full operational definition are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a single-group, open-label study with no randomized comparison. That design determines which statistical interpretations are available. The trial can describe participants’ observed experience, but there is no concurrent control group to estimate how outcomes differed under another condition. The registry record lists no analyses, so it does not document a statistical model, an adjusted comparison, or an inferential analysis for the primary outcome.

What does a count-based feasibility outcome represent?

In general, a count records how many participants meet a specified definition. For recruitment and retention, the count is meaningful only when the event is defined and the assessment window is clear. The registry describes the primary outcome as the number recruited and retained during a one-year study period, with participants as the unit. It does not report separate observed counts for recruitment and retention, define the retention criterion, or state a target for judging feasibility. The enrollment figure of 24 is recorded for the trial, but it is not itself a reported result for the combined recruitment-and-retention endpoint.

The registry classifies the outcome as binary and gives a count interpretation of participants with an event. A binary outcome ordinarily distinguishes whether a defined event occurred for each participant; a count summarizes participants meeting that definition. Here, the record does not explain how the binary classification relates to the stated number recruited and retained. Without an operational definition or analysis, readers should not infer a threshold, rate, or recruitment success criterion.

What can a confidence interval or p-value tell readers?

In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate; a wider interval indicates more uncertainty. A p-value, when reported, summarizes how compatible the observed data are with a specified null model, under the analysis assumptions. Neither measure replaces the estimate itself, and neither establishes that a finding is important or causal. No confidence interval or p-value for the primary outcome is reported in the registry record, so these tools cannot be used to characterize its precision or statistical evidence.

Why does the single-group design matter?

In general, a randomized comparison helps make groups comparable in expectation and allows an estimate of the contrast between assigned conditions. This trial had no comparator group and no randomized allocation, so that kind of contrast is unavailable. An observed change over time, if one had been reported, would not by itself identify what would have happened without the intervention. Open-label status also means treatment was known, which may affect subjective reporting or assessment in general. These are limitations of interpretation, not claims about what happened to participants in this study.

How should planning calculations be read?

General sample-size planning asks how many participants or events might be needed to detect a prespecified effect under stated assumptions. A planning illustration based on an observed effect is not a result from the trial and is not observed power. The illustration described for this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Those are planning assumptions; they do not describe this trial’s single-group design or establish that its protocol used those choices. The registry record does not report the trial’s own sample-size justification. No planning count should be interpreted as the number enrolled, a treatment result, or evidence that the study had adequate power.

Finally, the registry lists one outcome measure and no analyses. That is not enough to determine which participants were included in any outcome analysis, how missing observations were handled, or whether any adjustments were made. Those details would be necessary to assess the analysis in full, and they are not reported in the registry record.

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("N-acetylcysteine")
n      <- c(24)
events <- c(24)
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  N-acetylcysteine  24  24  100.0  85.8  100.0  86.2  100.0  86.3  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, identifying recruitment and retention feasibility as the primary outcome. It also says that tolerability, marijuana use, and reactivity to marijuana cues would be investigated, but does not list additional outcome measures or analyses in the record. The number of analyses is listed as 0. No statistical analysis plan, hierarchy of outcomes, or procedure for handling multiple comparisons is reported in the registry record.

Multiplicity arises when several outcomes, time points, or statistical tests are examined. In general, conducting many tests can increase the chance of obtaining a statistically notable result by chance if no adjustment or prespecified interpretation plan is used. Because no analyses or inferential results are listed, it is not possible to assess whether multiplicity was relevant to the actual analyses or how it was addressed. The stated intention to investigate several topics does not establish that statistical tests were conducted for them.

Missing-data handling is also not reported in the registry record. The primary outcome concerns retaining participants, but the record does not describe how incomplete follow-up, missed visits, withdrawal, or unavailable outcome measurements were treated. It does not say whether any imputation or sensitivity analysis was used. Without those details, readers cannot judge whether missing observations may have affected a reported estimate.

The analysis population is not reported either. The record does not state which participants would be included in each outcome analysis or how departures from the intended intervention would be handled. These omissions do not show that particular methods were or were not used; they mean the registry record does not document them. Clear reporting of outcome definitions, analysis populations, missing-data procedures, and multiplicity plans would be needed for a fuller statistical assessment.

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 non-serious adverse event terms

For the N-acetylcysteine group, the registry lists 24 participants at risk for serious adverse events and 0 participants affected. It lists 24 participants at risk for other adverse events and 15 participants affected. Deaths are listed as 0. These are participant counts, not a comparison between treatment groups.

The serious adverse-event figure means that no affected participants are recorded in this group for that category in the registry entry. It does not establish that no adverse experiences of any kind occurred: the record separately lists 15 participants affected by other adverse events. The registry does not give the terms for those other events in the information available, so their nature, severity, timing, and relationship to treatment cannot be assessed from these counts.

In general, safety counts need context, including how events were defined, collected, and assessed, and how long participants were followed. The registry record does not provide those details. Because the study had no comparator group, these figures cannot show whether the counts were higher or lower than they would have been under another condition. They are descriptive reports for the participants in the single group, not evidence of comparative safety.

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

This trial’s stated purpose was to examine the feasibility of conducting a study of N-acetylcysteine in adolescents with cannabis dependence. The registry identifies a single-group, open-label design, lists enrollment as 24, and describes recruitment and retention during a one-year period as the primary outcome. However, the observed primary outcome result is not reported in the registry record. The available information therefore does not establish whether recruitment and retention were judged feasible.

The registry description of the intervention specifies N-acetylcysteine 1200 mg twice daily during four weeks of participation. It says tolerability, marijuana use, and reactivity to marijuana cues would be investigated, but does not report results for those topics. The record lists no analyses. There is consequently no reported estimate of an intervention effect, no statistical comparison, and no measure of uncertainty for a clinical outcome.

The record does report safety counts: 0 participants with serious adverse events among 24 at risk, 15 participants with other adverse events among 24 at risk, and 0 deaths. These figures describe the registry’s entries for the N-acetylcysteine group. Without a comparator and further event details, they do not establish how the intervention compares with another condition or explain the nature of the other events.

More broadly, a single-group feasibility study can offer information about whether recruitment and study procedures can be carried out, if those outcomes are reported and defined. It cannot, by itself, provide the controlled contrast needed to attribute observed clinical changes to the intervention. In this record, the missing primary outcome result and lack of analysis details further limit interpretation. The evidence supports describing the study design and posted counts, but not a conclusion about clinical benefit, lack of benefit, or comparative safety.

14. Why This Trial Matters Statistically

Feasibility is a distinct statistical and design question from whether an intervention changes a clinical outcome. Before a larger comparative study can be interpreted, researchers need to know whether the target population can be recruited and whether participants can be retained long enough for planned assessments. A trial that measures recruitment and retention can therefore address practical uncertainties that clinical-effectiveness analyses do not answer.

This study is identified as a pilot and proof-of-concept feasibility preliminary study, and its primary outcome is recruitment and retention. That focus makes the distinction especially important: the enrollment figure of 24 is useful as a registry description of trial enrollment, but it cannot replace a reported retention result or a stated feasibility criterion. Because those outcome details are not reported in the registry record, readers cannot assess the primary feasibility question from the posted information.

The design also illustrates why the question must match the design. A single-group, open-label study can describe what happened among its participants, but it does not create a randomized comparison. Its stated feasibility aim differs from a causal question about whether N-acetylcysteine changes cannabis use or another clinical outcome. The registry’s indication that those topics would be investigated does not supply results for them.

Finally, transparent reporting of endpoint definitions, analysis methods, and missing-data handling helps readers distinguish an observed count from a planned measure and evaluate the uncertainty in a result. Those details are not reported in the registry record. The study is statistically informative as an example of a feasibility-focused design, while the available record leaves its central outcome unanswered.

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 primary limitation for interpreting the study is that its named endpoint—recruitment and retention feasibility—has no reported result in the registry record. Enrollment is listed as 24, but a separate retained count, definitions of recruitment and retention, and a criterion for feasibility are not reported. It is therefore not possible to judge the primary question from the posted outcome information.

The registry does not report analyses, statistical methods, an analysis population, or missing-data procedures. It also does not provide confidence intervals or p-values. These omissions prevent assessment of the precision of an outcome estimate, how incomplete data may have been treated, or which participants contributed to any analysis.

The single-group, open-label design is another limitation for interpreting clinical outcomes. There is no randomized comparator, so the study does not provide a direct estimate of the difference between N-acetylcysteine and another condition. Awareness of treatment may also influence reporting or assessment in general. These design features do not demonstrate that bias occurred, but they restrict causal interpretation.

The registry says that tolerability, marijuana use, and reactivity to marijuana cues would be investigated, yet it reports no results for those topics. Safety entries are limited to counts of participants affected; event terms and further context are not listed in the information available. The record also does not report the trial’s own sample-size justification or a detailed feasibility decision rule. These limitations apply to what can be concluded from the registry record and do not establish what may appear in other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Trial of N-Acetylcysteine in Cannabis Dependent Adolescents — NCT00542750.
• Registry record last updated 2018-05-23; status last verified 2018-04.
• Results first posted 2018-05-23.
• 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 1 and Phase 2, open-label, single-group study of N-acetylcysteine in adolescents with cannabis dependence. Enrollment is listed as 24. All participants were to receive N-acetylcysteine 1200 mg twice daily during four weeks of participation. The primary question concerned recruitment and retention during a one-year period.

The registry lists one outcome measure and no analyses. It does not report the primary feasibility result, clinical outcome results, or the analysis methods. The adverse-event entries list 0 participants with serious adverse events among 24 at risk, 15 participants with other adverse events among 24 at risk, and 0 deaths. With no comparator group, these are descriptive counts rather than comparative estimates.

The posted record establishes the study’s purpose and basic design, but leaves the primary outcome result and important analysis details unreported. It does not support a conclusion about clinical effects or comparative safety.