A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents (NCT05102591), a randomized phase 3 study. The primary outcome is Assessment of Recruitment Rate.

2. Clinical Question

The registry record concerns a pilot trial of a remote electrical neuromodulation device for children and adolescents experiencing acute migraine attacks in the emergency department. The trial also included a standard-of-care intravenous treatment strategy. Its primary question was about feasibility, measured through recruitment, rather than whether one treatment produced better clinical outcomes.

Clinical outcomes such as pain severity, pain freedom, sustained pain relief, and global impression of change were listed as secondary outcomes. Their numerical results are not reported in the registry record. The posted primary results therefore address the pace of recruitment in the two design phases, not comparative clinical benefit.

3. Trial Design

The registry identifies the study as randomized, triple masked, and crossover, with a phase designation of phase III. It also describes two recruitment periods: a parallel-group design phase and a crossover design phase. The reported enrollment was 22. The available record does not explain the masking roles or provide the detailed sequence and timing needed to reconstruct the crossover procedure.

The primary endpoint description says the design changed to crossover to address participant and recruitment concerns. In particular, the stated concern was that someone initially assigned to REN might not receive standard-of-care migraine treatment if REN was unsuccessful. The registry says recruitment rates for both phases were reported to assess whether changing to crossover design improved recruitment.

In the parallel-group phase, the reported mean recruitment rate was 1.1 participants per month, with a standard deviation of 1.5, for n=17. In the crossover phase, the mean was 0.6 participants per month, with a standard deviation of 1.0, for n=5. These are descriptive phase-specific summaries. The registry record does not report an inferential comparison between the rates or a confidence interval for either mean.

The primary outcome description says recruitment was evaluated monthly and at the end of recruitment, with the endpoint timing described as 2 years or once the final participant had completed the study. The record lists a study start of 2022-02-22, primary completion of 2024-03-01, and status as completed. It does not report the full recruitment calendar or monthly counts, so the mean and standard deviation cannot be independently reconstructed from the posted summaries.

The record lists ketorolac, metoclopramide, an active REN device, placebo, and a sham REN device among the interventions. It describes an initial treatment grouping and a crossover treatment grouping in the safety results. Full details of treatment allocation, period effects, washout, adherence, and the statistical handling of repeated measurements are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: During the parallel-group phase, 3 participants provided written informed consent but withdrew prior to being randomized. As such, 22 participants were enrolled in the entire study but 19 of those were randomized to a study treatment. During the crossover phase, participants were not required to receive the crossover treatment if well enough to go home after the initial treatment. Only 2 participants received the crossover treatment (both REN initially and Standard of Care as crossover).

Overall Study

Analysis population for the primary outcome, as defined in the registry: Number of participants who were screened, deemed eligible, and subsequently enrolled. Three (3) participants during the parallel-group design phase withdrew after consent but before being randomized/receiving study treatments. No other participants withdrew during the study.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline characteristics are reported per arm/group, separately for the parallel phase and crossover phase. No participants received the REN crossover treatment during the crossover phase as they were well enough to go home after the initial IV treatment (as per protocol). Both participants in the "REN Group First" arm of the crossover phase also received the SoC crossover treatment.

6. Primary Endpoint

The registry lists the primary outcome as Assessment of Recruitment Rate, measured over Evaluated monthly and at the end of recruitment (i.e., 2 years or once the final participant has completed the study).

The primary endpoint was recruitment rate, defined as the number of enrolled participants per month. The registry describes the relevant population as participants who were screened, deemed eligible, and subsequently enrolled. It states a target average recruitment rate of 1.5 participants per month.

Recruitment is a feasibility endpoint: it describes whether a trial can enroll participants at a pace considered relevant to its planning. It does not measure pain relief, safety, or comparative treatment effect. The registry says feasibility, together with secondary outcomes, was intended to provide preliminary data to help design and optimize a fully powered phase III randomized trial.

The reported mean was 1.1 participants per month during the parallel-group design phase and 0.6 participants per month during the crossover design phase. The associated standard deviations were 1.5 and 1.0, respectively. These summaries describe recruitment in each phase; they do not establish that the design change caused a difference in recruitment. The phase groups also differ in their reported n values, and no adjusted or inferential comparison is reported in the registry record.

The endpoint description notes that three participants withdrew after consent but before randomization or receiving study treatments during the parallel-group phase. It also states that no other participants withdrew during the study. The registry does not give monthly enrollment counts, a confidence interval for the mean recruitment rates, or a formal feasibility decision rule beyond the stated target.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure: recruitment rate, expressed as participants per month. The registry reports a mean and standard deviation for each design phase. A mean gives the average observed recruitment rate, while the standard deviation describes how much the observations vary around that average. These summaries are useful for describing recruitment, but they do not by themselves quantify the precision of the mean or establish a difference between phases.

In general, a confidence interval gives a range of values compatible with the observed data under a statistical model, and communicates uncertainty around an estimate. No confidence interval for either recruitment mean is reported in the registry record. Without the underlying monthly recruitment observations and a specified analysis, a reader cannot reconstruct one from the posted summary statistics alone.

The phase-specific results are 1.1 participants per month with standard deviation 1.5 for the parallel-group phase, and 0.6 participants per month with standard deviation 1.0 for the crossover phase. The record reports n=17 and n=5 for those summaries. It does not define whether these n values refer to people, months, or another unit of analysis for the recruitment-rate summaries. Consequently, the precise observational basis for each mean and standard deviation is not reported in the registry record.

A comparison of means would require a clearly defined estimand and analysis. For example, an analyst would need to know whether the intended contrast is between average rates across the two periods, whether time trends are accounted for, and how the change in study design is handled. Because the phases occurred at different times and the registry describes a design change between them, a simple unadjusted comparison would not separate a design effect from other differences between periods. The registry record does not report a formal test, model, adjustment, or confidence interval for a comparison of recruitment rates.

In general, standard deviations and standard errors serve different purposes. A standard deviation describes variability among observations; a standard error describes uncertainty in an estimated mean and depends on the analysis and amount of information. The registry reports standard deviations, not standard errors. The sample-size planning illustrations elsewhere are planning calculations based on an observed effect and stated assumptions; they are not observed power. Numerical planning results are not reported in the registry record, so no specific planning count can be interpreted.

The record identifies the study as randomized, triple masked, and crossover, and also reports a parallel-group phase. Randomization can help balance groups at assignment in a trial, while masking can reduce the influence of expectations on care or assessment. These are general methodological purposes; the registry does not report who was masked, the randomization procedure, or details sufficient to evaluate implementation. In a crossover design, participants may receive more than one treatment over time. General analyses of crossover data need to account for within-participant dependence and treatment period. The registry does not report the sequence, washout, period-specific outcome data, or statistical approach used for any crossover clinical outcome.

The primary outcome description states that recruitment rate was evaluated monthly and at the end of recruitment, described as 2 years or once the final participant had completed the study. The record gives only phase-level means and standard deviations, not the monthly series. With no monthly observations, readers cannot assess changes in recruitment over time, variability between months, or whether the mean reflects a stable rate.

The registry lists 12 outcome measures and 11 posted secondary outcomes. The listed secondary measures include reduction in pain severity, global impression of change, pain freedom, sustained pain freedom, changes on a 4-point pain severity scale between baseline and 2 hours post-intervention, sustained pain relief, screening and enrollment counts, and feedback from participants and staff. Numerical results for these clinical outcomes are not reported in the registry record. No outcome-specific effect estimates, standard errors, confidence intervals, or p-values are available for interpretation.

In general, over-dispersion occurs when observed variation is greater than a model assumes. It can make standard errors too small if an analysis does not accommodate the extra variability. The reported standard deviations describe variation in recruitment rates, but the record does not report a model or sufficient monthly data to evaluate over-dispersion. This concept therefore serves as general context, not a claim about an analysis conducted in this trial.

The registry record reports no analyses for the relevant comparison, and a two-arm recalculation is not available for the continuous endpoint. There is no sponsor-reported inferential estimate to compare with a recalculation. The most defensible reading is descriptive: the record gives phase-level recruitment summaries and a target, but does not provide the analysis details needed for a formal comparison or precision assessment.

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("Parallel-group Design", "Crossover Design")
n   <- c(17, 5)
m   <- c(1.1, 0.6)
sp  <- c(1.5, 1)
sd  <- sp      # posted standard deviations
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  Parallel-group Design  17  1.100  1.500  0.329  1.871
CARM  Crossover Design  5  0.600  1.000  -0.642  1.842

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 11 posted secondary outcomes. Multiple outcomes can raise multiplicity concerns because examining many outcomes may increase the chance of at least one apparently notable result by chance. In general, a prespecified hierarchy, adjustment, or clear distinction between primary and exploratory outcomes can help readers understand how multiple tests were handled. The registry record does not report a multiplicity strategy, an outcome hierarchy beyond identifying recruitment rate as primary, or a statistical analysis plan for the listed secondary outcomes.

Numerical results for the listed secondary clinical outcomes are not reported in the registry record. The record therefore does not permit assessment of missing outcome results, effect estimates, or uncertainty for those measures. It also does not report whether any secondary outcome was omitted, changed, or not estimable after data collection.

The primary outcome description states that three participants withdrew after consent but before randomization or receiving treatment during the parallel-group phase, and that no other participants withdrew during the study. The record does not provide a full participant-flow account, reasons for those withdrawals, or a description of how missing observations were handled. It does not state whether an intention-to-treat, per-protocol, or other analysis population was used for clinical outcomes.

For the recruitment endpoint, the record describes the target population as screened, eligible, and enrolled participants, but does not report monthly observations or missing-month handling. It is therefore not possible to determine from the registry whether all recruitment periods contributed complete data or how the phase summaries were constructed. The analysis populations and missing-data methods are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry reports serious adverse events and other adverse events separately for treatment groupings. For standard-of-care intravenous initial treatment across the parallel and crossover phases, 10 were at risk for serious adverse events and 0 were affected; 10 were at risk for other adverse events and 1 was affected. For REN initial treatment across the phases, 9 were at risk for serious adverse events and 0 were affected; 9 were at risk for other adverse events and 0 were affected.

For standard-of-care intravenous crossover treatment in the crossover phase, 2 were at risk for serious adverse events and 0 were affected; 2 were at risk for other adverse events and 0 were affected. The crossover-treatment REN group lists 0 at risk and 0 affected for both serious and other adverse events. The record reports 0 deaths in each group.

These are descriptive counts. The registry does not report serious adverse event terms, and the group sizes are limited, so zero reported serious events should not be read as proof that serious events cannot occur. The record does not provide event-level details or state whether the single other adverse event was considered treatment-related. The figures do not establish a comparative safety effect.

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

The main result is a feasibility description: recruitment averaged 1.1 participants per month in the parallel-group phase and 0.6 participants per month in the crossover phase. The stated target was an average of 1.5 participants per month. These results help describe the enrollment experience across the two design periods.

They do not establish whether REN improves acute migraine outcomes relative to standard-of-care intravenous treatment. The registry lists several clinical secondary outcomes, but numerical results for them are not reported in the registry record. Recruitment rate is not a proxy for pain relief or treatment safety.

The phase-specific means also do not establish that the switch to crossover design caused recruitment to change. The record reports the reason for changing design, but does not provide a formal comparison, uncertainty intervals, monthly recruitment data, or an analysis accounting for possible differences between periods. The summaries should therefore be treated as descriptive rather than causal.

The pilot was described as a source of preliminary data to help design and optimize a fully powered phase III randomized trial. Its results may be relevant to feasibility planning, but the record does not report a formal decision about whether the recruitment target was achieved. It also does not report a sample-size justification, interim analyses, or a complete statistical plan. Those omissions limit assessment of how the pilot’s findings were intended to guide later research.

The safety record lists no serious adverse events and no deaths in the reported groups, along with one other adverse event in the standard-of-care initial-treatment group. These counts are descriptive and do not establish that one strategy is safer. In particular, the registry does not report event details or a statistical comparison.

Accordingly, the posted results support an interpretation about recruitment and reported adverse-event counts only. They do not provide a basis for a clinical recommendation or a definitive conclusion about comparative treatment effects.

14. Why This Trial Matters Statistically

Feasibility is central to the interpretation of a pilot trial because the ability to recruit participants affects whether a larger study can be completed. The primary endpoint in this trial directly addresses recruitment pace, rather than treating a clinical outcome as the sole measure of success. The stated target of 1.5 participants per month gives the recruitment summaries a planning context.

The study also illustrates a design challenge in emergency-department research: the registry says the move to crossover was intended to address concerns about participants initially receiving REN without standard-of-care treatment if REN was unsuccessful. That concern affected recruitment planning and the trial’s design. The record reports recruitment separately by the parallel-group and crossover phases, which makes the feasibility experience visible, while leaving the effect of the design change uncertain.

Statistically, the phase-specific summaries are useful but limited. Means and standard deviations describe the recruitment experience, yet the absence of monthly observations, confidence intervals, and a formal comparison leaves uncertainty about variability over time and the distinction between phase and design effects. The posted information therefore demonstrates why transparent reporting of the analysis unit, time series, and decision rules can matter in a pilot study.

The trial is identified as phase III while also being described as a pilot intended to inform a fully powered phase III randomized trial. The registry record does not explain this designation. That distinction is important for readers: the primary endpoint and stated purpose are feasibility-oriented, and the posted results do not include comparative clinical outcome estimates. Interpretation should follow the outcomes that are actually reported rather than relying on the phase label alone.

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 available results are limited to recruitment summaries and adverse-event counts. Although the registry lists 12 outcome measures and 11 posted secondary outcomes, numerical results for the clinical secondary outcomes are not reported in the registry record. This prevents assessment of pain outcomes and other planned measures.

The recruitment results are presented by study-design phase. The record does not provide monthly recruitment counts, the exact observational basis of the reported n values, or a confidence interval or formal test comparing phases. Because the phases occurred at different times, the available summaries cannot isolate the effect of the design change from other differences over time.

Details needed to evaluate trial conduct and analysis are not reported in the registry record. These include the full randomization procedure, who was masked, the treatment sequence and crossover timing, handling of period effects, and the statistical methods used for clinical outcomes. A sample-size justification, interim analyses, and a statistical analysis plan are also not reported.

The primary outcome description reports three withdrawals after consent but before randomization or treatment during the parallel-group phase, with no other withdrawals during the study. It does not give a complete flow of participants through screening, eligibility, enrollment, randomization, treatment, and outcome assessment, or specify the analysis population and missing-data methods.

The safety results contain small reported at-risk group counts, no serious adverse events, and no deaths. The record does not provide serious-event terms or details about the single other adverse event. These data cannot establish comparative safety, and the absence of reported serious events should not be interpreted as evidence that risk is absent.

Finally, the trial is described as a pilot and its primary endpoint is feasibility, while the registry phase designation is phase III. The record does not explain that combination. The reported results should therefore be interpreted according to the stated recruitment objective, not as a definitive test of clinical effectiveness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Clinical Trial of a New Neuromodulation Device for Acute Attacks of Migraine in Children and Adolescents — NCT05102591.
• Registry record last updated 2025-03-12; status last verified 2025-02.
• Results first posted 2025-03-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed randomized, triple-masked pilot trial of a remote electrical neuromodulation device for acute migraine in children and adolescents visiting the emergency department. The model is listed as crossover, and the primary outcome description also reports a parallel-group design phase followed by a crossover phase. Enrollment was 22.

The primary endpoint was recruitment rate, defined as participants enrolled per month, with a stated target average of 1.5 participants per month. The reported mean recruitment rates were 1.1 participants per month in the parallel-group phase and 0.6 participants per month in the crossover phase. Numerical results for the listed clinical secondary outcomes are not reported in the registry record.

The registry reports no serious adverse events and no deaths in the listed groups, and one other adverse event in the standard-of-care initial-treatment group. It does not report a formal comparison of recruitment phases, clinical outcome estimates, or a complete statistical analysis plan.