Adjunctive Transcranial Stimulation to Reduce Impulsivity in Opiate Use Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjunctive Transcranial Stimulation to Reduce Impulsivity in Opiate Use Disorder (NCT05049460), a randomized na study. The primary outcome is Attentional Bias for Smoking Stimuli.

2. Clinical Question

The study concerns whether theta burst stimulation, used as an adjunct to participants’ existing care, changes attention to smoking and opioid cues relative to neutral stimuli. The registry summary also describes interest in cigarette and opioid craving. Participants were to complete a stress-induction procedure intended to reproduce environmental cues and stress associated with craving.

The primary endpoint is specifically attentional bias for smoking stimuli, not a direct measure of craving, opioid-cue attention, or clinical recovery. Its registry-record timeframe is baseline. That timing matters: baseline values describe the groups at the stated measurement point, rather than an outcome comparison after the stimulation sessions. The posted figures therefore do not by themselves answer whether the intervention changed attentional bias.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group study. Participants were allocated to active theta burst stimulation or sham TMS. The registry lists an enrollment of 23 and marks the study completed. The recorded study start is 2021-09-15, and the primary completion date is 2024-07-31. The phase is listed as NA.

The active intervention consisted of four theta burst stimulation sessions, amounting to 7200 pulses at 120% resting motor threshold. Neuronavigation and a processed resting-state brain scan were used for targeting. The sham group also received four sessions, with the same targeting approach described. The brief summary says all sessions were to take place on the same day; each session was expected to last approximately 10 minutes, with 50 minute intervals between sessions.

The primary outcome is attentional bias for smoking stimuli, measured at baseline. The task used cigarette and matched neutral images presented on a laptop, with an eye tracker recording fixation time. The registry also lists a secondary outcome concerning participants showing functional connectivity changes. It identifies 7 outcome measures, but the posted primary results do not include a post-intervention attentional-bias estimate or an inferential comparison between groups.

Randomization and double masking describe important features of the design, but the registry record does not report the allocation procedure, how masking was implemented or assessed, or the analysis plan. Those details should not be inferred from the design labels alone.

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:

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 Attentional Bias for Smoking Stimuli, measured over Baseline.

The primary endpoint is attentional bias for smoking stimuli, measured in milliseconds with a visual-probe task and eye tracking. Participants viewed cigarette images alongside matched neutral images. After each image pair disappeared, a visual probe appeared where one of the images had been. The endpoint description defines attentional bias as average fixation time on cigarette cues minus average fixation time on neutral cues.

This measure is used to quantify whether attention is directed differently toward smoking-related images than toward neutral images. It is a behavioral measure of attention in the task, not a direct measurement of craving, tobacco use, opioid use, or treatment response. The registry describes the endpoint as a mean and gives its timeframe as baseline.

For the active group, the posted baseline mean is 501.5 milliseconds, with a standard error of 145.2. For the sham group, the posted baseline mean is 406.7 milliseconds, with a standard error of 116.4. These are descriptive group summaries at baseline. The registry record does not report a post-session value for this endpoint or a statistical test of a between-group effect.

The endpoint’s interpretation depends on the task and its timing. Fixation behavior during a structured image task may characterize attention to those cues under the task conditions; it should not be treated as interchangeable with reported craving or behavior outside the task.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group design. Randomization is intended to allocate participants to study groups by chance, helping to reduce systematic differences in group composition. Double masking is intended to limit the influence of treatment knowledge on participants or study personnel. These design terms do not, by themselves, show how allocation and masking were carried out; those operational details are not reported in the registry record.

What does a group mean describe?

The primary endpoint is a continuous measure expressed in milliseconds. A mean summarizes the measurements in a group with a single central value. The active group’s posted baseline mean is 501.5 milliseconds, and the sham group’s is 406.7 milliseconds. A mean does not show the shape of the underlying observations or whether individual participants had similar or very different values. The registry record does not provide individual observations or a measure of participant-level spread such as a standard deviation.

What does the standard error describe?

The standard error describes how precisely a sample mean estimates the corresponding group mean under the assumptions of the statistical model. Smaller standard errors generally indicate more precise estimates; larger ones indicate greater uncertainty. The posted standard errors are 145.2 milliseconds for active intervention and 116.4 milliseconds for sham TMS. They are not measures of the variability among participants in the same way as a standard deviation. Confidence intervals can be constructed from standard errors using an appropriate method, but no confidence intervals are reported in the registry record, and none are reconstructed.

Why is a group contrast different from two group summaries?

A comparison of means addresses the contrast between groups, while each posted mean describes only its own group. Inferential interpretation of a contrast ordinarily depends on the estimated contrast and its uncertainty, together with the chosen analysis method. The registry record does not post an inferential analysis for this continuous endpoint. Consequently, it provides no test statistic, p-value, confidence interval for a contrast, or adjusted comparison to interpret. The values should not be converted into a claim about statistical significance or treatment effect.

Why does the endpoint timeframe matter?

The endpoint is recorded at baseline. A baseline summary can describe the groups at that measurement point, but it is not a measure of change following the intervention. An intervention effect would require an outcome assessment after treatment and an analysis that compares outcomes or changes between the randomized groups. No such primary-endpoint estimate is reported in the registry record. The baseline figures therefore cannot establish whether four sessions of stimulation altered attentional bias.

What can be said about the measurement?

The task records fixation time for cigarette and matched neutral images using an eye tracker. The registry defines the endpoint as the average fixation time on cigarette cues minus the average fixation time on neutral cues. This operational definition identifies the task-derived quantity being summarized. It does not make the measure a direct report of craving or a measure of behavior outside the task. In general, an endpoint’s meaning is bounded by how it was measured and the time at which it was collected.

How should planning calculations be understood?

In general, a sample-size planning illustration asks how many participants per arm might be needed to detect an effect under stated assumptions. The registry describes illustrations based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning scenarios, not observed power and not evidence that the original study was designed around those assumptions. The registry record does not report the trial’s own sample-size justification. No planning estimate should be treated as a trial result.

The registry marks the study as randomized and double-blind, but does not report the statistical model, any covariate adjustment, the handling of repeated measurements, or the method used for missing values. Without those details and an inferential result, interpretation should remain descriptive.

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("Active Intervention", "Sham TMS")
n   <- c(8, 7)
m   <- c(501.53, 406.7)
sp  <- c(145.24, 116.41)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Active Intervention  8  501.530  410.801  158.092  844.968
CARM  Sham TMS  7  406.700  307.992  121.855  691.545

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures and identifies one posted secondary outcome: the number of participants showing functional connectivity changes. The primary endpoint is attentional bias for smoking stimuli. Because several outcomes are listed, interpretation of a collection of statistical tests would ordinarily need to consider multiplicity: when many hypotheses are tested, the chance of at least one apparently unusual result can increase. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a complete analysis plan. No adjustment should be assumed.

The record lists no posted analyses for the primary continuous endpoint. It therefore does not report a model, an analysis population, or an approach to repeated measurements. The registry lists enrollment of 23, while the baseline endpoint summaries have group sample sizes of 8 and 7. The reasons these endpoint counts differ from overall enrollment are not reported in the registry record. It is not possible to determine from the posted information whether the difference reflects unavailable measurements, eligibility for a particular analysis, exclusions, or another cause.

Missing-data handling is also not reported. The record does not state how missing outcome measurements were treated, whether any imputation was used, or whether the analysis followed an intention-to-treat approach. These omissions matter because the interpretation of group summaries can depend on which participants contributed measurements and how incomplete data were handled.

The registry’s lack of a posted analysis does not establish that no analysis occurred outside the registry; it means an analysis is not reported in the registry record. Without additional documented information, conclusions about multiplicity control, analysis populations, and missing-data methods remain unavailable.

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 1% reporting threshold.

For serious adverse events, the registry reports 0 affected participants in the active intervention group, with 8 at risk, and 0 affected participants in the sham TMS group, with 7 at risk. It also reports 0 deaths in each group. For other adverse events, the reported counts are 0 affected participants among 8 at risk in the active group and 0 among 7 at risk in the sham group. No serious adverse-event terms are listed.

These figures describe what the registry reports for the groups and event categories. A count of zero affected participants is not proof that an intervention is free of risk. The figures relate to the participants represented in these safety summaries, and the registry record does not provide further detail about event surveillance, definitions, duration of follow-up, or completeness of reporting. The safety counts should therefore be read as reported observations, not as a guarantee about safety in other settings or populations.

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

The posted primary outcome results describe baseline attentional bias for smoking stimuli in the two randomized groups. The active group’s mean is 501.5 milliseconds, with a standard error of 145.2; the sham group’s mean is 406.7 milliseconds, with a standard error of 116.4. These data provide descriptive information about the baseline task measurements summarized in the registry.

They do not show a change after theta burst stimulation. The timeframe is baseline, and no post-intervention estimate or inferential comparison for this primary outcome is reported. The registry record therefore does not establish whether stimulation altered attentional bias or whether the groups differed as a result of treatment. The baseline numerical ordering should not be interpreted as evidence for or against an intervention effect.

The measure also has a specific scope. It reflects fixation time on smoking-related and neutral images during a computer-based task. It is not itself a measure of cigarette consumption, opioid use, craving, treatment retention, or functional recovery. Although the study summary describes broader interests involving opioid cues and craving, those questions cannot be answered by the posted primary endpoint values alone.

Finally, the uncertainty around the group means and the reasons for the endpoint denominators are not fully characterized in the registry record. The posted standard errors convey uncertainty in the means, but no confidence interval or test of a group contrast is reported. The results should be interpreted as limited baseline summaries rather than a complete account of efficacy, safety, or clinical outcomes.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a treatment question and a baseline description. A randomized comparison is designed to evaluate groups assigned to different conditions, but the posted primary outcome is measured at baseline. As a result, the reported values characterize the groups before any post-session comparison is available in the registry record. Recognizing the endpoint timing prevents baseline summaries from being mistaken for evidence about treatment effects.

The study also illustrates why an estimate and its uncertainty need to be read together. Group means offer a concise description of the measured endpoint, while standard errors describe precision of those mean estimates. Neither alone supplies an inferential conclusion about a between-group contrast. A contrast estimate and its uncertainty, with a documented analysis method, would be needed for that interpretation; they are not reported for this primary endpoint.

Another important issue is the distinction between overall enrollment and the sample sizes attached to an outcome. The registry lists enrollment of 23, while the baseline endpoint summaries use group sample sizes of 8 and 7. The reasons for the endpoint counts are not reported. Clear accounting of analysis populations and missing measurements is important for judging how well a result represents the randomized groups.

Finally, the trial’s multiple listed outcomes make transparent outcome selection and multiplicity methods relevant. The registry record does not report those methods. These are not reasons to dismiss the study; they define what can and cannot be concluded from the results currently recorded.

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 main limitation for interpreting the primary outcome is that its reported timeframe is baseline. The posted values do not include a post-intervention measurement or an estimate of change, so they cannot address whether the intervention altered attentional bias. No inferential comparison for the endpoint is reported either.

The endpoint summaries represent group sample sizes of 8 and 7, while overall enrollment is recorded as 23. The registry record does not explain this difference. Information about participant flow, missing measurements, exclusions, and the analysis population is not reported, limiting assessment of how the summaries relate to the randomized groups.

The registry also does not report confidence intervals, a statistical model, covariate adjustment, or methods for handling missing data and multiple outcomes. The standard errors communicate some uncertainty around the means, but they do not replace a reported analysis of the group contrast. The absence of these details prevents a fuller assessment of precision and robustness.

The task measures eye fixation on smoking and neutral images. That task-specific endpoint should not be generalized to craving, opioid-cue attention, substance use, or clinical functioning. The registry summary describes those broader interests, but the primary results are limited to baseline smoking-stimulus attentional bias. Further details about safety monitoring and follow-up are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adjunctive Transcranial Stimulation to Reduce Impulsivity in Opiate Use Disorder — NCT05049460.
• Registry record last updated 2025-10-22; status last verified 2025-10.
• Results first posted 2025-10-22.
• 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

NCT05049460 is a completed, randomized, double-blind, parallel-group study of theta burst stimulation versus sham TMS in people with tobacco use disorder and comorbid opioid use disorder who were stable on buprenorphine treatment. The registry lists enrollment of 23, a start date of 2021-09-15, and a primary completion date of 2024-07-31.

The primary endpoint is baseline attentional bias for smoking stimuli, measured in milliseconds with a visual-probe task and eye tracking. The active group’s reported mean is 501.5 milliseconds (standard error 145.2; n 8); the sham group’s mean is 406.7 milliseconds (standard error 116.4; n 7). The registry record does not report an inferential comparison or post-intervention result for this endpoint.

Safety summaries report no affected participants for serious or other adverse events in either group, and no deaths. The registry does not report the trial’s own sample-size justification, the statistical analysis plan, or reasons for the endpoint sample sizes.