This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Enhancing Self Regulation Among Smokers (NCT04161144), a randomized phase 2 study. The primary outcome is Craving Levels in Response to Cue.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04161144 |
| Phase | Phase 2 |
| Condition | Smoking Cessation, Smoking, Cigarette, Nicotine Dependence |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Medical University of South Carolina |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned individuals with nicotine dependence and was registered under conditions including smoking cessation, cigarette smoking, and nicotine dependence. The primary outcome description refers to patients whose data were entered under a cue condition at the study visits. The record does not give more detailed eligibility criteria or describe the characteristics of participants at baseline. It records enrollment of 22 participants, but does not provide enough information to characterize the population beyond these descriptions.
Intervention
The experimental intervention was rapamycin, also called sirolimus. The intervention description identifies a 15mg dose, delivered as three 5mg pills. The brief summary says the study examined the medication's effects on responses to smoking cues. It also describes its use in this study as investigational for nicotine dependence; the record does not establish it as a smoking-cessation treatment.
Comparator
The comparator was placebo, described in the study summary as an inactive substance. The arm description says participants in either group received three 5mg pills and that some were randomized to study medication while others were randomized to placebo. The record does not describe additional features of the placebo or specify whether allocation was equal.
Primary question
The central question was whether craving levels in response to a cue differed between the rapamycin and placebo groups across study visit 1 (Baseline; day 0), visit 2 (day 7), and visit 3 (day 14). Craving was recorded on a scale from 0, least amount of craving, to 100, highest amount of craving. The registry record does not report a single comparison across these visits or the resulting group values, so the direction and precision of any difference cannot be assessed from the recorded primary outcome.
3. Trial Design
This was a phase 2, randomized, triple-masked, parallel-group study, listed as completed. The sponsor was the Medical University of South Carolina. The registry record lists enrollment of 22 and gives the study start as 2018-10-01 and primary completion as 2019-12-20. The title frames the work as a translational clinical neuroscience study of a novel medication, with the stated focus on altering memories that increase relapse risk among smokers.
Participants were assigned to rapamycin (sirolimus) or placebo. The medication arm is described as rapamycin 15mg (sirolimus); the placebo arm is described as placebo. Both arm descriptions state that participants received three 5mg pills from a nurse in the Research Nexus. Although the study is marked randomized and triple-masked, the registry record does not identify which people or roles were masked, describe the sequence-generation method, or specify allocation concealment. It also does not give the allocation ratio. The equal-allocation assumption used for planning illustrations should not be read as evidence that the actual groups were allocated equally.
The parallel design indicates separate groups assigned to the two interventions, rather than a crossover design in which participants receive both. The primary outcome description identifies craving scores under a cue condition at baseline and follow-up visits on day 7 and day 14. Average cigarettes smoked per day is listed as a secondary outcome. The record indicates three outcome measures, but it does not provide a full description of every measure or a complete account of which participants contributed data at each visit. No detailed protocol, analysis plan, or account of trial conduct 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.
Overall Study
| Stage | Rapamycin 15mg (Sirolimus) | Placebo |
|---|---|---|
| STARTED | 12 | 10 |
| COMPLETED | 11 | 9 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Rapamycin 15mg (Sirolimus) | Placebo |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Protocol Violation | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Data entered are the number of participants under the cue condition at study visit 1 (Baseline; day 0), visit 2 (day 7) and visit 3 (day 14)
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.
| Characteristic | Unit | Rapamycin 15mg (Sirolimus) | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 12 | 10 | 22 | |
| Age, Continuous | years | 51.3 (SD 11.3) | 47.1 (SD 15.2) | 49.4 (SD 13.0) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 5 |
| Sex: Female, Male: Male | Participants | 9 | 8 | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 | 1 | 5 |
| Race (NIH/OMB): White | Participants | 8 | 8 | 16 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 12 | 10 | 22 |
| Cigarettes Per Day | Cigarettes Per Day | 21.5 (SD 9.5) | 19.7 (SD 10.3) | 20.7 (SD 9.7) |
6. Primary Endpoint
The registry lists the primary outcome as Craving Levels in Response to Cue, measured over Study visit 1 (Baseline; day 0), visit 2 (day 7) and visit 3 (day 14).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome was titled “Craving Levels in Response to Cue.” It measured participants' reported craving on a scale from 0 to 100, where 0 represents the least amount of craving and 100 the highest amount. The registry identifies the summary parameter as a mean and the dispersion measure as a standard deviation. Measurements were associated with study visit 1 (Baseline; day 0), visit 2 (day 7), and visit 3 (day 14), with the outcome description referring to participants under the cue condition.
Craving is a subjective response, so a scale provides a structured way to record and summarize participants' reports. A mean describes the group's average score; the standard deviation describes how spread out scores are around that average. In general, these summaries can help characterize both the typical response and variation between participants. They do not, by themselves, show how groups compare or whether any difference is precise.
The measure concerns craving in response to cues, not smoking behavior itself. Average cigarettes smoked per day appears as a secondary outcome, which is conceptually distinct from a craving score. The registry record does not give the actual means or standard deviations at the visits, the number contributing data to each measurement, or a defined primary contrast between the groups. It therefore does not permit interpretation of the magnitude or uncertainty of a primary-outcome effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary outcome and its measurement schedule, but it does not report a single primary-outcome comparison. The stated reason is that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the record does not provide an effect estimate for craving, a confidence interval, or a p-value for a single comparison. It is not possible from the recorded primary outcome to say whether average craving scores differed between the groups, how large a difference might have been, or how precisely it was estimated.
The omission matters because the outcome is repeated across study visits. A group mean at one visit would answer a different question from a contrast in change over time, and a contrast at one follow-up would differ from an overall comparison across visits. The registry record does not specify which of these questions was intended as the primary inferential target. Nor does it report values for the cue-condition scores. Without those details, readers should avoid treating a particular visit or pattern as the trial's primary result.
Enrollment was 22, and the adverse-event record lists groups of 12 for rapamycin and 10 for placebo. Those group counts do not supply the missing outcome data. In particular, the record does not say how many participants had craving measurements at each visit, whether any observations were missing, or how missing measurements were handled. The recorded enrollment cannot be assumed to equal the analysis population for every visit or outcome.
The registry lists average cigarettes smoked per day as a secondary outcome, but it does not include a result for that measure in the registry record for interpretation. The outcome count is three, while detailed results are not reported for the measures. No outcome finding should be inferred from the study title, the stated objective, or the completion status. Completion indicates the study's recorded status; it is not evidence that the intervention altered craving or smoking behavior.
The safety record lists no serious adverse events and no deaths in either group, alongside other adverse-event counts. Those observations describe the recorded events in this study; without further detail they do not establish a comparative safety effect. The registry record also does not provide an inferential analysis for safety. Overall, the data available for interpretation are descriptive and incomplete for assessing treatment effects. The absence of a reported primary comparison should be read as a limitation of the registry record, not as evidence that the groups were identical or that no effect occurred.
9. Statistical Methods Explained
What does a mean summarize?
The primary outcome is identified as a mean of a continuous craving score. In general, a mean is the arithmetic average of the measured values in a group. It can be useful for describing the typical score, but it does not reveal whether individual scores are tightly clustered or widely dispersed. The registry also identifies standard deviation as the measure of dispersion. In general, a standard deviation describes variability around the mean, in the same units as the measure. Neither statistic alone establishes whether groups differ beyond what could arise from sampling variability.
The scale runs from 0 to 100, with the endpoints defined in the registry record. A mean score can be interpreted in relation to those anchors, but the meaning of a difference also depends on the context and on how the score behaves in the study population. No threshold for a meaningful change is reported in the registry record. The recorded scale description therefore supports understanding what was measured, but not deciding what magnitude would be important to participants or researchers.
Why does the visit schedule matter?
Measurements were scheduled at baseline, day 7, and day 14. Repeated measurements from the same participant are generally related: a participant's score at one visit may be more similar to that participant's score at another visit than to another participant's score. In general, statistical methods for repeated observations need to account for that dependence when estimating uncertainty. Treating all recorded scores as independent when they are not can make uncertainty estimates unreliable.
Different analyses can address different scientific questions. A comparison at a follow-up visit asks whether groups differ at that time. A change-from-baseline comparison asks whether their changes differ. A model of the full visit pattern can address whether the groups follow different trajectories. These are general distinctions, not a description of the method used in this study. The registry record does not report which comparison or model was prespecified or used, and the recorded primary outcome was not reduced to one comparison.
What would an effect estimate and confidence interval tell a reader?
In general, an effect estimate describes the size and direction of a contrast between groups. A confidence interval conveys the statistical uncertainty around that estimate: narrower intervals indicate greater precision, while wider intervals indicate less precision. The interval does not replace consideration of the estimate itself, the outcome scale, or the study's design. Here, the registry record does not report a primary effect estimate or confidence interval. Thus, the precision of a group contrast cannot be evaluated from the recorded primary outcome.
A p-value, when reported, addresses how compatible the observed data are with a specified statistical model and null hypothesis. It is not a measure of effect size, clinical importance, or the probability that a treatment works. The registry record does not report a primary p-value. No conclusion about statistical significance can be drawn from the absence of such a value.
How should planning illustrations be read?
The planning assumptions describe illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not proof that the trial was designed using those assumptions. The record explicitly distinguishes the illustrations from the trial's own design. The equal-allocation assumption is also not a report of the trial's actual allocation.
In general, a sample-size calculation estimates the number of participants per arm needed under assumptions about effect size, variability, significance level, and desired power. Changing assumptions changes the resulting planning estimate. Such an estimate is not an observed treatment effect and cannot establish how likely the completed study was to detect an effect. The stated illustrations are planning exercises, not observed power. The registry entries do not give the illustration outputs or the observed effect values, so no numerical planning requirement can be interpreted.
Why can variability affect planning?
In general, greater variability in a continuous outcome makes group differences harder to estimate precisely, all else being equal. Standard deviation is therefore relevant both to describing the data and to planning a study. If observations are repeated within participants, the relationship between measurements can also affect the precision of an analysis. These general principles explain why means, standard deviations, visit patterns, and analysis choices matter together; they do not establish which approach the study used. The registry record does not report a statistical analysis plan, a model for repeated measures, or assumptions about within-participant correlation.
What is not documented about the analysis?
The record does not describe the primary inferential contrast, adjustment variables, handling of missing observations, or the analysis population. It lists zero analyses. That entry does not substitute for a complete statistical plan or indicate what analyses may have been conducted outside the registry record. Without a specified analysis and its results, readers cannot assess the primary effect, its uncertainty, or whether the reported analysis followed a prespecified plan. These are limits on what can be concluded from the registry record, rather than evidence that any particular method was or was not used.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome covers several visits, and the registry explicitly indicates that it was not reduced to a single comparison. When an outcome is examined at multiple visits or through multiple contrasts, general statistical practice recognizes a multiplicity issue: the more questions tested, the greater the opportunity for a chance finding if each is assessed separately without an appropriate plan. Possible responses include prespecifying a primary contrast, using a method that accounts for multiple comparisons, or treating analyses as exploratory. This is general context, not a claim about the strategy used in this study.
The registry record does not report a multiplicity adjustment, a hierarchy of outcome tests, or a prespecified contrast. It also does not give p-values or confidence intervals for the primary outcome. Accordingly, the record does not support an assessment of how multiplicity was handled or whether a particular contrast was intended to carry confirmatory weight. The presence of multiple visits alone does not tell readers which statistical approach was applied.
Missing-data information is also not reported in the registry record. The outcome description identifies three visit times, but does not state how many observations were available at each, why any measurements might be absent, or what method was used to address missingness. In general, missing-data methods rely on assumptions about why values are missing; those assumptions can affect estimates and their uncertainty. No particular missingness mechanism or method should be inferred.
The analysis population is not reported in the registry record. It is therefore unclear whether results, if analyzed, were intended to include all randomized participants, participants who completed visits, or another defined group. This distinction is important because the participants included in an analysis can affect the interpretation of a randomized comparison. The record's enrollment number does not establish the population used for each outcome or visit. These gaps limit assessment of the reliability and reproducibility of any treatment-effect analysis.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Rapamycin 15mg (Sirolimus) | 0 | 12 | 0.0% |
| Placebo | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rapamycin 15mg (Sirolimus) | 0 of 12 |
| Placebo | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rapamycin 15mg (Sirolimus) | 6 of 12 |
| Placebo | 5 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rapamycin 15mg (Sirolimus) | Placebo |
|---|---|---|---|
| Headache | Nervous system disorders | 5 of 12 | 2 of 10 |
| Increased Thirst | General disorders | 2 of 12 | 2 of 10 |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | 1 of 12 | 2 of 10 |
| Restlessness | Psychiatric disorders | 2 of 12 | 1 of 10 |
| Dry Mouth | General disorders | 1 of 12 | 1 of 10 |
| Taste Anomoly | General disorders | 1 of 12 | 1 of 10 |
| weakness/Fatigue | General disorders | 2 of 12 | 0 of 10 |
| Nightmares/Vivid Dreams | Psychiatric disorders | 2 of 12 | 0 of 10 |
The registry records serious adverse events for each group. In the rapamycin 15mg (sirolimus) group, 0 serious adverse events were recorded among 12 participants at risk; in the placebo group, 0 were recorded among 10 participants at risk. The record lists 0 deaths in each group. It lists 6 other adverse events in the rapamycin group and 5 in the placebo group, with 12 and 10 participants at risk, respectively.
These are event counts as recorded, not a statistical comparison. No percentages or rates are calculated here, and the counts alone do not establish whether the interventions differ in safety. The registry record does not provide descriptions of the other adverse events, their severity, timing, relationship to study medication, or the method used to collect and classify them. It also does not report a statistical analysis of adverse events. No serious adverse-event terms are listed in the registry record.
A zero serious-event count in this study means no such events were recorded in the listed groups; it does not prove that a serious event could not occur. The size and scope of the study, the event definitions, and the follow-up relevant to safety should be considered, but further details are not reported in the registry record. These counts should be read as a limited descriptive account rather than a comprehensive estimate of risk.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, triple-masked, parallel phase 2 study compared rapamycin (sirolimus) with placebo and focused its primary outcome on craving scores in response to cues at baseline and follow-up visits. It also records average cigarettes smoked per day as a secondary outcome. Those details describe the research question and measurement plan; they are not evidence that either intervention changed craving or smoking behavior.
The primary outcome values and a single comparison are not reported in the registry record. As a result, the record does not show the size or direction of a group difference, its precision, or whether a statistical test supported a difference. It cannot establish that the groups were equivalent, because equivalence requires a defined margin and an analysis designed to evaluate it. Nor can a missing result be interpreted as proof of no effect.
The study's completion status and enrollment count do not resolve these uncertainties. Completion says that the study is marked completed in the record; it does not supply outcome estimates. Enrollment describes the recorded study size, but does not tell readers how many participants contributed usable measurements at each visit or how missing observations were addressed. The safety counts are also descriptive and do not establish a comparative safety effect.
General conclusions about a medication's effects would require interpretable outcome estimates, uncertainty measures, and details of the analysis and population. The registry record does not report those elements for the primary comparison. Its brief summary identifies the use of rapamycin for nicotine dependence as investigational, and the record does not justify treating it as an established smoking-cessation treatment. Interpretation should therefore remain limited to the study's design, the outcome it intended to measure, and the information actually recorded.
13. Why This Trial Matters Statistically
This study raises a statistical question that is common in clinical research: how should a repeated, continuous outcome be compared between randomized groups? The craving scale was scheduled at baseline and two follow-up visits, so the analysis could potentially focus on a particular visit, change from baseline, or the pattern over time. Those choices answer different questions. Prespecifying the intended contrast is important because readers need to know which estimate represents the main treatment question.
The registry record does not reduce the primary outcome to one comparison or report the underlying values. That makes the limitations of registry reporting especially consequential. A study's design and outcome definitions can be clear while its treatment-effect evidence remains unavailable for interpretation. Transparency about the analysis, missing observations, and uncertainty would help readers distinguish an inconclusive result from an absent result and evaluate how the data support any claim.
The study also illustrates why outcome type matters. Craving is a continuous, self-reported score, while average cigarettes smoked per day is a behavioral measure listed as secondary. These outcomes address related but distinct concepts; results for one would not automatically establish an effect on the other. General statistical interpretation requires matching an estimate to the outcome and time frame it represents.
Finally, planning illustrations should not be confused with evidence from the completed trial. Their assumptions can show how planning depends on an effect size and variability, but the record distinguishes those illustrations from the trial's own design. This distinction helps prevent retrospective calculations from being misread as the study's prespecified sample-size rationale or as observed power. The key statistical lesson is to keep design, planning, analysis, and results separate when interpreting a clinical trial.
14. 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 interpretation is that the registry record does not report primary-outcome values or one defined comparison. The measure is described at several visits, but the intended contrast and its statistical analysis are not stated. Without means, standard deviations, an effect estimate, or an uncertainty interval, readers cannot evaluate the magnitude, direction, or precision of a craving difference.
The record does not describe how many participants contributed outcome data at each visit, whether observations were missing, or how missing data were handled. It does not specify the analysis population or provide a statistical analysis plan. These omissions prevent assessment of whether the analysis accounted for repeated observations and whether the results, if analyzed, followed a prespecified approach. The record lists three outcome measures, but does not provide complete descriptions and results for them.
Further design details are not reported in the registry record, including eligibility criteria, participant characteristics, the actual allocation ratio, and which roles were masked. The fact that the study was randomized and triple-masked does not fill in those details. The record also does not explain how the cue condition was implemented or give information to interpret the scale beyond its stated endpoints.
Safety information is limited to counts of serious and other adverse events and deaths. Descriptions, timing, severity, attribution, and analytic comparisons are not reported. Finally, the study is identified as phase 2 and its use of rapamycin for nicotine dependence as investigational. The registry record does not provide evidence sufficient to establish the medication's effect on craving or smoking behavior, or to support broad conclusions beyond the recorded study description.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Enhancing Self Regulation Among Smokers — NCT04161144.
- Registry record last updated 2021-03-09; status last verified 2021-03.
- Results first posted 2021-03-09.
- 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.
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18. Record Summary
NCT04161144, titled “Enhancing Self Regulation Among Smokers,” is a completed randomized, triple-masked, parallel phase 2 study sponsored by the Medical University of South Carolina. The record lists enrollment of 22 and compares rapamycin (sirolimus) with placebo. The primary outcome is craving level in response to a cue, measured on a 0-to-100 scale at baseline, day 7, and day 14. Average cigarettes smoked per day is listed as a secondary outcome.
The registry record does not report a single primary-outcome comparison, primary estimates, or their uncertainty. It records 0 serious adverse events and 0 deaths in each group, and lists other adverse-event counts of 6 for rapamycin and 5 for placebo. Details needed to assess the outcome analysis, missing data, and analysis population are not reported in the registry record.