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 Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Opioid Use Disorder (NCT04495673), a randomized na study. The primary outcome is (A1) Average Number of Serious Adverse Events in Active and Sham Groups..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04495673 |
| Phase | NA |
| Condition | Opioid-Related Disorders, Heroin Dependence, Morphine Dependence |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 9 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Minnesota |
| Results posted | Yes |
2. Clinical Question
Population
The registry lists opioid-related disorders, heroin dependence and morphine dependence as conditions of interest. It does not report participant characteristics such as age, clinical history or baseline substance use in the record. The registry enrollment is 9, while the posted primary endpoint results include 3.0 participants in the active arm and 2.0 in the sham arm. The relationship between those endpoint counts and total enrollment is not reported in the registry record.
Intervention
The active intervention combined transcranial direct current stimulation, or tDCS, directed at the dorsolateral prefrontal cortex (DLPFC), with simultaneous cognitive training. The study’s broader objective was to investigate whether this pairing could enhance functional connectivity between the DLPFC and nucleus accumbens and potentially support cognition and reduced substance use. Those objectives describe the study rationale, not the posted primary endpoint.
Comparator
The comparison group received sham tDCS with simultaneous cognitive training. Thus, the arms differed in active versus sham stimulation while both included cognitive training. The registry identifies the study as randomized, parallel and triple masked. The particular people or roles included in the masking are not reported in the registry record.
Primary question
The posted primary outcome is the average number of serious adverse events in the active and sham groups, assessed at 2months post-intervention. The reported means are 0.0 in each arm, with a standard deviation of 0.0 in each. This is a safety-focused measure; it is not a direct measure of functional connectivity, cognition or substance use. The posted results do not provide a statistical comparison between arms, so they do not quantify whether the observed outcomes differ between the intervention strategies.
3. Trial Design
The registry describes a randomized, parallel-group trial with triple masking. Participants were assigned to tDCS with cognitive training or sham tDCS with cognitive training. The record does not identify which study roles were masked, describe the randomization procedure, or report details of allocation concealment. Those design details are not reported in the registry record.
The study was listed as phase NA and sponsored by the University of Minnesota. The registry enrollment is 9. The recorded start date is 2021-01-11, the primary completion date is 2022-02-22, and the current status is TERMINATED. A reason for termination is not reported in the registry record. These registry entries describe the registered study status and timeline; they do not establish why the study ended or how many participants completed every follow-up assessment.
The active arm paired DLPFC stimulation with cognitive training, while the comparator paired sham stimulation with the same training. This active-control structure can help distinguish the contribution of active stimulation from the contribution of training, provided the groups are otherwise comparably treated and the relevant outcomes are measured and analyzed. The registry record does not report enough procedural detail to assess those conditions fully.
The brief summary emphasizes a longer-term research goal of developing paired neuromodulation approaches and describes functional connectivity as a target. However, the posted primary outcome is the average number of serious adverse events. A secondary outcome is change in scaled score on the Digit Symbol Task. The record lists 5 outcome measures, but only one secondary outcome is posted in the information. The distinction between the study’s scientific motivation and its posted outcome data is important when interpreting what the results can address.
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 | tDCS With Cognitive Training | Sham tDCS With Cognitive Training |
|---|---|---|
| STARTED | 5 | 4 |
| COMPLETED | 3 | 2 |
| NOT COMPLETED | 2 | 2 |
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 | tDCS With Cognitive Training | Sham tDCS With Cognitive Training | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 4 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 | 4 | 9 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 4 | 4 | 8 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 3 | 1 | 4 |
| 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 | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as (A1) Average Number of Serious Adverse Events in Active and Sham Groups., measured over 2months post-intervention.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Number of adverse events |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the average number of serious adverse events in the active and sham groups at 2months post-intervention. The registry description says participants were monitored from the first intervention session through the final follow-up visit. Monitoring used the Symptom Rating Questionnaire, a Medication/Medical Update Interview and medical chart review. Serious adverse events were defined to include death, life-threatening incidents, initial or prolonged hospitalization, disability or permanent damage, congenital anomaly or birth defect, and events requiring intervention to prevent permanent impairment or damage.
A safety endpoint is used to describe serious harms observed during a specified monitoring period. The registry’s stated interpretation is that a lower number indicates fewer serious adverse events. The posted means are 0.0 for tDCS with cognitive training and 0.0 for sham tDCS with cognitive training; both posted standard deviations are 0.0. These summaries describe the recorded endpoint values, not all possible risks or outcomes outside the monitoring period. The separate safety listing reports participants at risk and serious events, but its denominators differ from the arm counts attached to the primary endpoint results. The record does not explain that difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary endpoint summaries are the same in the two arms: the mean number of serious adverse events is 0.0 in each, and the standard deviation is 0.0 in each. For the endpoint records, the active arm has n 3.0 and the sham arm has n 2.0. The registry therefore reports no observed variation in this measure within either of those posted groups. This is a description of the submitted summaries, not evidence that the underlying risks are identical.
No comparative analysis is posted. The record reports 0 analysis records and does not provide a treatment-effect estimate, confidence interval or p-value for the primary endpoint. Consequently, readers cannot use these results to assess the precision of a between-arm difference or whether the data are compatible with a range of possible differences. A confidence interval, in general, describes the uncertainty around an estimated quantity under the assumptions of the analysis; no such interval is reported for this comparison.
The safety listing adds context but should not be treated as interchangeable with the primary endpoint summaries. It reports 0 serious adverse events among 5 participants at risk in the active group and 0 among 4 participants at risk in the sham group. It also reports 0 deaths in each group. The listed numbers at risk differ from the primary endpoint arm counts, and the registry record does not explain why. The listing also reports other adverse events: 4 in the active group and 1 in the sham group. The record does not provide the terms for those other events in the summary. These counts should be read as posted, without deriving rates or assuming that the groups had the same observation time or completeness of follow-up.
The registry enrollment is 9, but the primary endpoint summaries include fewer participants than that enrollment figure. The record does not explain whether the difference reflects missing outcome data, a different analysis population, incomplete reporting, or another reason. It would be inappropriate to infer the reasons or to treat the endpoint sample as a complete account of all enrolled participants.
Overall, the posted information documents zero serious adverse events in the summarized groups, but it does not support a precise comparative conclusion. A small number of endpoint records, the unexplained denominator difference, and the lack of a reported analysis limit the strength of statistical interpretation. The termination status and absence of a stated reason are additional context, not an explanation of the outcome summaries.
9. Statistical Methods Explained
The registry identifies a continuous primary outcome summarized as a mean with standard deviation. In general, a mean represents the arithmetic center of observed values, while a standard deviation describes how spread out those values are around the mean. Here, the measured quantity is a number of serious adverse events, even though the posted endpoint is represented using a continuous-summary format. The reported means and standard deviations are 0.0 in both arms. No participant-level observations or alternative summaries are posted in the record.
What does the mean and standard deviation convey?
The mean can provide a compact summary of an outcome across participants, but it does not show the distribution of individual values. The standard deviation gives information about observed variability, not uncertainty in the mean itself. Uncertainty in an estimated mean is usually assessed with an interval or a model-based standard error; neither is reported for this endpoint. A standard deviation of 0.0 indicates no variation in the values represented by that posted group summary. It does not establish that all possible participants would have the same experience, nor does it describe outcomes beyond the recorded observations.
Why is an event count different from a comparative effect?
Reporting each arm’s mean is descriptive. To estimate a treatment contrast, an analysis would need to define how the groups are compared and account for the endpoint’s properties and the study design. The record does not post such an estimate or describe a model for the primary outcome. Therefore, no conclusion about the magnitude or precision of a difference between active and sham stimulation can be drawn from a reported inferential analysis. General statistical practice distinguishes the observed summaries from a formal contrast that quantifies uncertainty.
Counts of adverse events also require careful interpretation. Participants may experience different numbers or types of events, and the number of events is not necessarily the same as the number of participants with at least one event. The registry lists serious events and other adverse events separately, but does not supply event-level detail for the other events in this summary. It would be inappropriate to convert the posted counts into rates or percentages without a clear denominator and a defined observation period for each participant.
Why does over-dispersion matter in general?
For count outcomes, some statistical models make assumptions about how the variability relates to the mean. Over-dispersion occurs when observed variability is greater than a model assumes. If a model fails to account for over-dispersion, uncertainty estimates can be too small, making results appear more precise than they are. This is a general issue for count data, not a reported finding about this study. With the posted standard deviations at 0.0 and the small endpoint group counts, the record does not provide enough information to assess a count-data model or its assumptions.
What can confidence intervals and p-values add?
In general, a confidence interval communicates a range of values compatible with an estimate under the model and assumptions used. A p-value summarizes how unusual data at least as discrepant as those observed would be under a specified null model. Neither is a measure of clinical importance by itself, and neither can substitute for the estimated effect and its uncertainty. The registry record reports no confidence interval or p-value for the primary comparison. It also does not report a formal analysis method, covariate adjustment, or a prespecified hypothesis test for this outcome. Those details are not reported in the registry record.
The record lists the study as randomized, which identifies the intended design basis for comparing groups. Randomization can reduce systematic differences between groups on average, but it does not guarantee that small groups will be balanced on every characteristic. The posted endpoint group counts are limited, and baseline characteristics are not included in the information. No adjustment should be assumed.
How should planning illustrations be read?
Any sample-size figures based on an observed effect are planning illustrations, not observed trial results and not observed power. In general, such illustrations depend on their assumptions, including the chosen effect to detect, allocation, significance level and statistical approximation. The registry record does not report the trial’s own sample-size justification or design assumptions. The primary endpoint data do not include a reported comparative effect, and the record does not provide analysis results from which to judge the precision of an observed treatment contrast. A planning calculation cannot repair those gaps or show that the trial had adequate information for its registered question.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 5 outcome measures and 1 posted secondary outcome: changes in scaled score on the Digit Symbol Task. The primary endpoint concerns serious adverse events. The record does not report a multiplicity strategy, such as a prespecified hierarchy among outcomes or an adjustment for testing multiple hypotheses. With no posted analysis records, it is not possible to assess how multiple outcomes or comparisons were handled. Whether multiplicity adjustment was planned or applied is not reported in the registry record.
Missing-data handling is also not described. The registry enrollment is 9, whereas the primary endpoint arm counts are n 3.0 and n 2.0; the safety listing gives 5 and 4 participants at risk. The relationship among these counts is not explained. The record does not report how many participants were assessed at each visit, whether any outcome values were missing, why values might be missing, or whether missing values were imputed. No assumptions about missingness or sensitivity analyses are reported in the registry record.
The analysis population is not specified. The record does not say whether the posted endpoint summaries use all randomized participants, participants who received an intervention, participants with observed endpoint data, or another population. It also does not describe exclusions after randomization or adherence criteria. These omissions matter because the population included in an analysis affects what the result represents, particularly when group sizes are limited and the posted denominators do not align. No specific analysis population or missing-data procedure should be inferred from the arm summaries alone.
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 |
|---|---|---|---|
| tDCS With Cognitive Training | 0 | 5 | 0.0% |
| Sham tDCS With Cognitive Training | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| tDCS With Cognitive Training | 0 of 5 |
| Sham tDCS With Cognitive Training | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| tDCS With Cognitive Training | 4 of 5 |
| Sham tDCS With Cognitive Training | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | tDCS With Cognitive Training | Sham tDCS With Cognitive Training |
|---|---|---|---|
| poor concentration | General disorders | 4 of 5 | 1 of 4 |
| itching sensation | General disorders | 3 of 5 | 1 of 4 |
| sleepiness/fatigue | General disorders | 3 of 5 | 1 of 4 |
| tingling sensation | General disorders | 2 of 5 | 1 of 4 |
| acute mood change | General disorders | 2 of 5 | 1 of 4 |
| burning sensation | General disorders | 2 of 5 | 0 of 4 |
| skin redness | General disorders | 2 of 5 | 0 of 4 |
| Headache | General disorders | 1 of 5 | 0 of 4 |
| neck pain | Musculoskeletal and connective tissue disorders | 1 of 5 | 0 of 4 |
| Nausea | General disorders | 1 of 5 | 0 of 4 |
The primary endpoint summaries report a mean of 0.0 serious adverse events in each arm and a standard deviation of 0.0 in each. The associated endpoint counts are n 3.0 for tDCS with cognitive training and n 2.0 for sham tDCS with cognitive training. Separately, the safety listing reports 0 serious events among 5 participants at risk in the active group and 0 among 4 participants at risk in the sham group; deaths are listed as 0 in both groups. The record does not explain why these at-risk counts differ from the endpoint counts.
The safety listing also reports 4 other adverse events in the active group and 1 in the sham group. These are event counts, and the record does not provide the corresponding event descriptions in the summary. They should not be interpreted as numbers of participants affected unless the registry explicitly establishes that relationship. The monitoring period ran from the first intervention session to the final follow-up visit, described as 2months post-intervention. No event count can establish the absence of harms outside that observation period. The figures describe what was posted; they do not prove equivalent safety between groups or quantify the uncertainty around a group difference.
12. What the Result Does, and Does Not, Mean
The results mean that the registry’s posted primary summaries contain a mean of 0.0 serious adverse events for each intervention group, with a standard deviation of 0.0 in each group. The separate safety listing records no serious adverse events and no deaths in either group. These are the principal descriptive safety findings in the posted data. They do not provide a formal estimate of the difference between active and sham tDCS, and no confidence interval or p-value is reported for such a comparison.
The results do not establish that the interventions have identical safety profiles. A finding of no recorded serious events in a small set of endpoint records cannot rule out events that were not observed, not recorded or not represented in those summaries. The record does not explain the difference between the primary endpoint counts and the safety-listing denominators, and it does not report missing-data handling or the analysis population. These uncertainties limit how broadly the figures can be interpreted.
The primary endpoint also does not answer the study’s broader scientific questions about functional connectivity, cognition or substance use. The study summary describes the aim of pairing DLPFC stimulation with cognitive training, but the posted primary outcome is serious adverse events. The listed secondary outcome concerns change in Digit Symbol Task scaled score, but the registry record does not provide a posted result for it. There is no reported comparative analysis of functional connectivity or substance use in the results.
The terminated status indicates the registry’s current status for the trial. The reason for termination is not reported in the registry record, so it should not be attributed to the observed safety counts or any presumed efficacy finding. The responsible reading is narrow: the posted summaries record no serious adverse events in the groups with reported safety data, while leaving substantial uncertainty about the comparison and the scope of the available outcome data.
13. Why This Trial Matters Statistically
This trial is statistically instructive because the broad scientific objective and the posted primary outcome are not the same thing. The study summary focuses on paired neuromodulation, functional connectivity, cognition and potential effects on substance use. The primary registered measure is average serious adverse events. Keeping those questions distinct prevents a safety summary from being interpreted as evidence about connectivity or substance use.
It also illustrates why denominators matter. The primary endpoint summaries are attached to n 3.0 and n 2.0, while the safety listing reports 5 and 4 participants at risk. Both sets of figures may be valid for their respective records, but the registry does not explain their relationship. Without that explanation, readers cannot determine the precise analysis population or reconcile the different counts. Reporting clear denominators and participant flow is essential for interpreting outcome summaries.
The absence of a comparative estimate is another central statistical feature. Similar-looking arm means do not by themselves provide a confidence interval, a test of a prespecified hypothesis, or a measure of precision. The registry reports no analysis records, so the posted results support a descriptive account rather than an inferential comparison. This distinction is especially important when the endpoint group counts are limited.
Finally, the registry’s terminated status and the lack of a reported reason show why transparent reporting of study progress matters. The status alone does not explain what happened or establish whether results are biased. Statistical interpretation depends on details such as follow-up, missingness, outcome definitions and analysis populations, several of which are not reported in the registry record. Readers can therefore recognize the information that is available while keeping conclusions proportional to its limits.
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.
Several limitations are specific to the posted record. First, the registry enrollment is 9, but the endpoint summaries include n 3.0 in the active arm and n 2.0 in the sham arm. The safety listing separately reports 5 and 4 participants at risk. The record does not explain these differing counts, so the number of participants represented in each result and the reasons for any differences cannot be determined.
Second, no analysis records are posted. There is no reported treatment contrast, confidence interval, p-value or inferential model for the primary outcome. The means and standard deviations alone cannot establish a between-group difference or its precision. The record also does not describe missing-data methods, analysis populations, baseline characteristics, or sensitivity analyses. Whether these details were planned or conducted is not reported in the registry record.
Third, the primary endpoint is a safety measure, whereas the study summary emphasizes functional connectivity, cognition and substance use. The posted primary results therefore do not directly address those broader objectives. Although a change in Digit Symbol Task scaled score is listed as a secondary outcome, its result is not included in the record. The record lists 5 outcome measures but only one secondary outcome is posted in this information.
Finally, the study is marked TERMINATED, but no reason is reported. The masking roles, randomization details, sample-size justification and multiplicity plan are also not reported in the registry record. These omissions do not show that any particular procedure was absent; they limit what can be assessed from the posted information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Opioid Use Disorder — NCT04495673.
- Registry record last updated 2025-07-10; status last verified 2025-06.
- Results first posted 2025-07-10.
- 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
The registry describes a randomized, parallel, triple-masked study of tDCS with cognitive training versus sham tDCS with cognitive training for opioid-related disorders. Enrollment is listed as 9, and the study status is TERMINATED. Its primary outcome is the average number of serious adverse events at 2months post-intervention.
The posted primary means and standard deviations are 0.0 in both arms, with endpoint counts of n 3.0 and n 2.0. The safety listing reports 0 serious adverse events among 5 participants at risk in the active group and among 4 in the sham group, as well as 0 deaths in each group. It also lists 4 other adverse events in the active group and 1 in the sham group. No comparative analysis is posted. The reasons for termination, differing denominators, and methods for missing data or analysis populations are not reported in the registry record.