The Effects of Cranial Electrotherapy Stimulation (CES) on Brain Function, Brain Chemistry and Mood: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Cranial Electrotherapy Stimulation (CES) on Brain Function, Brain Chemistry and Mood (NCT01860677), a randomized na study. The primary outcome is BOLD fMRI (Neural Activation Patterns/Brain Function) Among Participants Who Completed Both Active and Sham Stimulation Visits.

2. Clinical Question

In practical terms, the study was designed to examine a brain-imaging signal and related brain-function measures, rather than to report a clinical symptom result as its primary endpoint. The listed secondary outcomes include brain activation patterns in the active arm and changes in mood-rating measures in that arm. The registry record gives no results for these secondary outcomes. Therefore, the question can be described from the planned measures and design, but the posted record cannot answer it with an observed treatment-effect estimate.

3. Trial Design

This was a randomized, triple-masked crossover study of the Fisher Wallace Cranial Stimulator. The registry lists enrollment of 8 and labels the condition as Mood. A crossover design means that participants are intended to receive more than one study condition, allowing measurements under different conditions to be compared within the same participant. Here, the primary outcome title refers to participants completing both active and sham stimulation visits. The record does not provide the order of those visits, the method used to assign their order, or whether a washout interval was used.

The active condition involved a device described as generating micro currents using a series of radio frequencies. The sham condition used a device identical in appearance that did not deliver current. The registry labels masking as triple, but does not identify which groups of people were masked or describe how masking was maintained. Those details are not reported in the registry record.

The primary outcome was planned around BOLD functional MRI, with a pre-treatment measurement and a measurement after 20 minutes of CES. The timeframe says measurement occurred within 30 minutes after treatment concluded, with pre-treatment at least 20 minutes before the end of treatment. The record does not describe the task used during imaging or the timing and sequence of each visit in further detail.

The study is marked completed, but completion status does not establish that all planned measurements were collected. For the primary outcome, the registry explicitly says data were not collected. It lists 4 outcome measures and 0 analyses. The reason for the absence of primary-outcome data, participant flow, withdrawals, and the number completing each visit are not reported in the registry record. This leaves the design identifiable, but prevents assessment of how closely the completed study followed the intended crossover comparison.

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.

First Intervention (1 Day)

Second Intervention (1 Day)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Data were not collected

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 BOLD fMRI (Neural Activation Patterns/Brain Function) Among Participants Who Completed Both Active and Sham Stimulation Visits, measured over within 30 minutes after CES treatment concluded; pre-treatment is at least 20 minutes before end of treatment.

The primary endpoint was BOLD fMRI, described as neural activation patterns or brain function during task performance. BOLD functional MRI measures changes in the blood-oxygenation signal associated with brain activity. In general, it is used as an indirect measure of neural response: it captures a signal related to changes in blood flow and oxygen use rather than directly recording the activity of individual neurons.

The planned outcome description refers to quantitative changes in activation patterns after 20 minutes of CES compared with pre-treatment. Its timeframe places the post-treatment measurement within 30 minutes after treatment ended and says the pre-treatment measurement was at least 20 minutes before treatment ended. The outcome title specifies participants who completed both active and sham visits, which is consistent with the crossover design. The record does not give the task details, the precise image-processing procedure, or the way the active and sham observations were to be combined into a primary estimate.

The description also defines a coupling ratio as percent change in cerebral blood flow divided by percent change in cerebral metabolic rate of oxygen consumption. That definition identifies a possible physiological summary, but the registry gives no observed ratio or other endpoint value. The primary outcome’s population field states that data were not collected. Consequently, the record explains what the endpoint was intended to measure and why imaging could be used to examine brain-function changes, but it provides no observed primary result to interpret.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help turn measurements into estimates that answer a study question. For this study, the crucial distinction is between the planned design and the evidence actually available in the registry. The record describes randomization, masking, a crossover model, and an imaging outcome, but states that primary-outcome data were not collected and lists 0 analyses. The analysis method used for a primary estimate is therefore not reported in the registry record.

What does randomization contribute?

In general, randomization uses a chance-based process to assign study conditions or their order. Its purpose is to reduce systematic differences in the way assignments are made. In a crossover study, it may be used to assign the sequence in which participants receive active and sham conditions. The record labels the study randomized, but the randomization procedure and sequence allocation are not reported in the registry record. It is therefore not possible to assess how allocation was generated or concealed.

How does a crossover comparison work?

In general, a crossover design compares measurements from the same participant under different conditions. Because each participant can serve as their own comparison, stable characteristics shared across visits are less likely to explain a within-participant difference. This benefit depends on having usable measurements under the conditions being compared and on accounting for the paired nature of the data. It also depends on design features such as treatment order and possible carryover from an earlier condition. The registry record does not report the visit sequence, washout arrangements, or an analysis method for paired observations. Since the primary outcome data were not collected, no within-participant contrast is available.

What does masking mean for interpretation?

Masking is intended to limit expectations or knowledge of treatment assignment from influencing care, measurement, or assessment. The record calls the study triple-masked and describes a sham device that looked identical to the active device but delivered no current. It does not say which people were masked, how masking was maintained, or whether masking success was assessed. These omissions do not show that masking failed; they limit the detail available for evaluating how it was implemented.

What would an effect estimate and confidence interval show?

In general, an effect estimate summarizes the observed contrast between conditions, while a confidence interval describes the uncertainty around that estimate under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but neither establishes clinical importance by itself. Here there is no reported primary estimate or interval because the record says primary data were not collected. There is consequently no basis in the posted record for describing the direction, magnitude, or precision of the planned BOLD fMRI contrast.

What role do analysis assumptions play?

Statistical analysis depends on assumptions about how measurements vary and how observations relate to each other. For example, a method for independent groups would not automatically reflect the pairing created by a crossover design. A method also needs to match the outcome scale and the structure of the collected data. These are general principles, not a description of the analysis used in this trial. The analysis approach, model specification, handling of repeated measurements, and adjustments for baseline values are not reported in the registry record.

The sample-size assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of an observed effect. These are assumptions for an illustration and do not establish the trial’s own planning rationale. The sample-size justification is not reported in the registry record. Any displayed participant-per-arm figures are planning illustrations, not observed power and not evidence that the study detected an effect. Since the primary outcome has several categories or time points and is not reduced to one comparison, there is no single primary contrast available to interpret from the record.

In general, a p-value describes how compatible data are with a specified null model under the assumptions of a test; it is not the probability that a treatment works or that the null hypothesis is true. The record reports no primary analysis or p-value, and no such result should be inferred from study completion or from the design description. Likewise, the record does not state whether analyses were planned to be adjusted or unadjusted, what covariates might have been used, or how multiple outcomes would have been handled.

For a crossover study, analysts may also need to consider period effects, treatment-order effects, and carryover. These are general design considerations: a participant’s measurement could differ across visits for reasons other than the assigned condition. The appropriate evaluation depends on design and data details. The registry does not report a plan for these considerations. With no primary outcome data, their possible influence cannot be assessed from the posted results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the BOLD fMRI primary outcome and secondary outcomes involving brain activation and mood-rating scales. The record lists 0 analyses. It does not report a statistical plan describing which comparisons were confirmatory, how outcomes or time points would be prioritized, or whether any adjustment for multiple testing was planned.

In general, testing multiple outcomes or multiple time points can increase the chance of finding at least one apparently notable result by chance. Multiplicity methods can address that issue, but the suitable approach depends on the study’s scientific questions and planned comparisons. No adjustment method is reported in the registry record. Because there are no posted outcome analyses, there is also no multiplicity-adjusted or unadjusted result to interpret.

For missing data, the key reported fact is that the primary outcome data were not collected. This is different from a report that values were collected but missing for some participants: the registry does not identify an analyzable primary dataset. The reason the data were not collected, whether any partial measurements existed, and whether collection stopped before or after imaging visits are not reported in the registry record.

The record does not describe imputation, exclusion rules, sensitivity analyses, or other missing-data procedures. It also does not report an analysis population, such as a defined set of randomized participants or participants with complete visits. Although the outcome title refers to those who completed both active and sham visits, the number of such participants is not reported. These gaps prevent assessment of how participant flow or missing measurements might affect a treatment estimate. No estimate can be recovered from the registry’s design description alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event summary lists 0 serious events among 8 at risk for active stimulation and 0 among 1 at risk for sham stimulation. It also lists 0 other events in each displayed risk set. These are the counts shown in the registry record; they should be read alongside the different denominators rather than as evidence that the conditions had equally complete safety observation.

The study is a crossover, but the adverse-event summary presents group-specific risk sets of different sizes. The record does not explain how those denominators were defined, whether they represent participants, exposures, or a particular observation period, or why the sham group has 1 at risk. It is not appropriate to infer an unreported denominator or treat these entries as a straightforward parallel-group comparison.

The deaths entries are null, so death counts are not reported in the registry record. The record also does not give event descriptions, observation duration, severity grading beyond the serious/other categories, or details of how adverse events were collected. A zero count in a small displayed risk set does not establish that an event cannot occur or that all relevant harms were captured. These figures are descriptive entries, not a complete safety evaluation and not evidence about the primary brain-imaging outcome.

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

This record is informative about the study’s intended design and measurement, but it does not provide an observed primary result. The study was randomized, triple-masked, and crossover, with active and sham stimulation visits and a planned BOLD fMRI outcome. The primary outcome description specifies a comparison of neural activation patterns after CES with pre-treatment measurements. The registry’s population field says that data were not collected.

Accordingly, the posted record does not show whether the BOLD signal changed, whether active and sham conditions differed, or whether any measured change was precise or consistent. It gives no primary effect estimate, confidence interval, or statistical test. The secondary outcomes are listed, but their results are not reported either. It would be inaccurate to turn the design description into a conclusion about the direction or size of an effect.

The enrollment of 8 indicates the number listed as enrolled, not the number with complete outcome measurements. The registry does not report the number completing both visits or the number with usable scans. The different risk sets in the adverse-event summary also should not be used to infer participant completion for the primary endpoint.

In general, a study’s ability to answer its question depends on collecting the planned measurements and analyzing them in a way that reflects the design. A crossover comparison can be useful when within-participant data are available, but that general feature cannot substitute for missing outcome data. Similarly, an illustrative sample-size calculation cannot supply an effect estimate, and it is not observed power.

The result this record supports is therefore limited: it documents a completed study with a stated design and planned brain-imaging question, while reporting no collected primary outcome data and no analyses. It neither demonstrates a primary effect nor demonstrates the absence of one. That distinction is essential when interpreting a registry entry without posted efficacy results.

13. Why This Trial Matters Statistically

This trial is statistically notable because its design and planned endpoint are described, yet the registry does not report the outcome data needed to evaluate the central question. That contrast illustrates why a trial’s design, completion status, and results are separate pieces of evidence. A completed record can still lack the measurements needed for an effect estimate.

The crossover structure also makes the intended comparison methodologically distinctive. In general, within-participant comparisons can control for stable differences between participants, but the data need to be available across conditions and analyzed with their paired structure in mind. The record identifies active and sham visits but does not report visit order, carryover handling, or a statistical model. Since primary data were not collected, these design strengths or challenges cannot be evaluated empirically.

The endpoint itself underscores that statistical interpretation depends on knowing what was measured. BOLD fMRI is an indirect physiological measure, and the record defines a coupling ratio involving changes in cerebral blood flow and oxygen consumption. Yet no observed value is available. A detailed endpoint definition does not establish that the endpoint changed or that a change would be precisely estimated.

The registry also shows why safety summaries require attention to denominators. The active and sham risk sets are not the same size, and the record does not explain their construction. Reading the event counts without that context could overstate what the summary can support.

More broadly, this study is a reminder to distinguish planned analyses from reported analyses, and planning illustrations from observed results. The record lists 0 analyses and does not give a sample-size justification or a statistical plan. These absences constrain interpretation, but they do not tell us why the data were not collected. A careful statistical reading should make that boundary explicit rather than fill it with assumptions.

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 most direct limitation is that the registry says primary-outcome data were not collected. As a result, the planned BOLD fMRI endpoint has no reported result, and the record cannot support an estimate of the primary contrast. The registry also lists 0 analyses, so it provides no statistical analysis of the primary outcome.

Enrollment was 8, but the number completing both active and sham visits is not reported in the registry record. Nor does the record provide participant flow, withdrawals, usable imaging counts, or reasons for noncollection. Without that information, it is not possible to determine how the enrolled group relates to the planned primary-outcome population.

Several design details are also absent. The record does not report the randomization sequence method, which people were masked, treatment order, washout arrangements, or a plan to address period or carryover effects. It does not describe the imaging task, image-processing procedures, or the statistical model for repeated measurements. The statistical analysis plan, sample-size justification, and interim-analysis details are not reported in the registry record.

The outcome list includes brain-imaging and mood-rating measures, but results for those secondary outcomes are not reported. The record does not state how multiplicity would be handled, what analysis population would be used, or how any missing values would be treated. These limitations are specific to the information available for this study; they should not be treated as evidence about what investigators may have done outside the registry.

Finally, safety entries show different risk-set sizes for active and sham stimulation, without an explanation of the denominators. The deaths entries are null. This limits how much can be inferred from the adverse-event summary. Together, the absent primary data and limited methodological detail mean that the record is more useful for describing the planned study than for evaluating its results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effects of Cranial Electrotherapy Stimulation (CES) on Brain Function, Brain Chemistry and Mood — NCT01860677.
• Registry record last updated 2017-06-14; status last verified 2017-05.
• Results first posted 2017-06-14.
• 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.

18. Record Summary

The registry describes NCT01860677 as a completed, randomized, triple-masked crossover study of the Fisher Wallace Cranial Stimulator, with enrollment of 8 and the condition listed as Mood. Active stimulation was compared with a sham device that did not deliver current. The primary outcome was planned as a BOLD fMRI measure of neural activation patterns after CES compared with pre-treatment.

The record states that primary-outcome data were not collected and lists 0 analyses. It gives no primary or secondary outcome estimates. The adverse-event summary lists 0 serious events in each displayed risk set, with 8 at risk for active stimulation and 1 at risk for sham stimulation; deaths are not reported in the registry record. The study design and intended endpoint are documented, but the posted record does not provide results with which to estimate the planned treatment contrast.