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 Study of Two Digital Therapeutics for the Prevention of Episodic Migraine (NCT05853900), a randomized na study. The primary outcome is Change in MMD (Monthly Migraine Days).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05853900 |
| Phase | NA |
| Condition | Migraine, Episodic Migraine, Headache |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 568 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Click Therapeutics, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled late adolescents and adults with episodic migraine. The primary analysis population is described as the intent-to-treat population: randomized participants analyzed according to their assigned intervention and recorded in the database. The registry reports enrollment of 568, while the primary outcome summaries list 266 participants for Arm A and 264 for Arm B. The registry record does not explain the relationship between those counts.
Intervention
Arm A received Mobile application A, identified in the outcome summaries as CT-132. The registry describes it as a software-based intervention for preventive treatment of episodic migraine. The listed intervention is the ReMMi-D Digital Therapeutic.
Comparator
Arm B received Mobile application B, identified in the outcome summaries as a digital control. The registry describes it as an investigational digital therapeutic being studied for prevention of episodic migraine. The registry record does not report further details about how the applications differed or what participants experienced in the digital control condition.
Primary question
The primary question was whether the mean change in monthly migraine days from the 28-day run-in period to the 28 days spanning Week 9 through Week 12 differed between the assigned digital interventions. The registry posts a least-squares mean change and a 95% confidence interval for each arm. It does not report a direct primary between-arm estimate or test, so the arm-specific summaries alone do not establish the size or statistical uncertainty of the primary contrast.
3. Trial Design
The registry describes a randomized, double-blind, parallel-group virtual study of two digital therapeutics for episodic migraine prevention in late adolescents and adults. The study status is completed. The recorded start date is 2023-03-28, and the primary completion date is 2024-05-07. The phase is listed as NA. The registry record gives an enrollment of 568.
Participants were assigned to Arm A, Mobile application A (CT-132), or Arm B, Mobile application B (digital control). The registry identifies the study intervention as the ReMMi-D Digital Therapeutic. Although the trial is described as double-blind, the registry record does not explain how masking was implemented for participants, investigators, or other study personnel, or how masking was assessed. Details of the virtual study procedures and the applications’ specific features are not reported in the registry record.
The primary outcome measures change in monthly migraine days from a 28-day run-in period to Week 12, using the previous 28 days, specified as Week 9 through Week 12. The primary population is described as the intent-to-treat population, based on randomized assignment. The posted arm summaries list 266 participants in Arm A and 264 in Arm B. Safety summaries use an at-risk count of 278 in each arm. The registry record does not explain the differences in these analysis counts or how missing observations were handled.
The record lists nine outcome measures and eight posted secondary outcomes, but the statistical analysis details are limited. A formal sample-size justification, allocation ratio, randomization method, interim-analysis plan, and detailed analysis plan are not reported in the registry record. The posted planning illustration is based on observed effects and is not evidence of the trial’s original design assumptions.
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 | Arm A (CT-132) | Arm B (Digital Control) |
|---|---|---|
| STARTED | 285 | 283 |
| COMPLETED | 255 | 262 |
| NOT COMPLETED | 30 | 21 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat Population, all enrolled participants who were randomized, based on the assigned intervention in the randomization and recorded in the database.
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 | Arm A (CT-132) | Arm B (Digital Control) | Total |
|---|---|---|---|---|
| Participants analysed | 285 | 283 | 568 | |
| Age, Continuous | years | 38.4 (SD 10.4) | 38.9 (SD 10.3) | 38.7 (SD 10.3) |
| Sex/Gender, Customized: Female | Participants | 263 | 265 | 528 |
| Sex/Gender, Customized: Male | Participants | 12 | 13 | 25 |
| Sex/Gender, Customized: Other | Participants | 10 | 5 | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 10 | 13 | 23 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 275 | 270 | 545 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 6 | 6 | 12 |
| Race (NIH/OMB): White | Participants | 269 | 261 | 530 |
| Race (NIH/OMB): More than one race | Participants | 8 | 12 | 20 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 285 | 283 | 568 |
6. Primary Endpoint
The registry lists the primary outcome as Change in MMD (Monthly Migraine Days), measured over Baseline (28-day Run-in Period) to Week 12 (previous 28 days, Week 9 through Week 12).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | migraine days per month |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in monthly migraine days (MMD) from baseline, defined as the 28-day run-in period, to Week 12. The Week 12 assessment uses the previous 28 days, specifically Week 9 through Week 12. MMD expresses the frequency of migraine days over a month-long period, so change in this measure captures whether the recorded number of migraine days shifted over the study interval. The unit is migraine days per month.
The registry reports least-squares mean changes for each arm, with 95% confidence intervals. A least-squares mean is an estimate from a statistical model; depending on the model, it can account for specified factors rather than simply representing the arithmetic average of the observed values. However, the registry record does not report the model specification, adjustment factors, or covariance assumptions. Readers therefore cannot determine from the record which adjustments, if any, contributed to these estimates.
The endpoint is useful for comparing changes in migraine frequency across assigned groups, but the comparison itself is essential to the trial question. An arm-specific change describes the observed estimate within that arm; it does not by itself show how much the arms differ. The record gives a confidence interval for each arm’s estimate but does not post a direct primary between-arm estimate, its confidence interval, or a primary p-value. The precision of the individual arm estimates can be read from their intervals, but the uncertainty in the contrast cannot be recovered from those intervals alone without additional statistical information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
From baseline to Week 12, the posted least-squares mean change in MMD was -3.04 migraine days per month in Arm A, with a 95% confidence interval from -3.49 to -2.58. In Arm B, the posted change was -2.14, with a 95% confidence interval from -2.59 to -1.69. These are arm-specific estimates. The registry record does not post the primary between-arm contrast, its confidence interval, or its test result.
Both arm estimates are negative, indicating a reduction from baseline in the estimated number of monthly migraine days within each arm. That description is not equivalent to an estimated treatment effect relative to the digital control. A direct comparison is needed to quantify the difference between assigned interventions, and a confidence interval for that contrast is needed to understand its precision. The arm-specific confidence intervals describe uncertainty around each arm’s estimate; they do not substitute for uncertainty around the difference between arms.
The endpoint summaries list 266 participants in Arm A and 264 in Arm B. The record defines the primary population as randomized participants analyzed according to assigned intervention, but it does not explain the analysis counts or the handling of missing outcome data. The safety summaries list different at-risk counts. These counts should not be assumed to represent the same analysis population or to explain one another.
The secondary outcome summaries add context, but they do not fill the reporting gap for the primary contrast. Some posted secondary outcomes include recalculated, unadjusted comparisons based on summary statistics; these are not the sponsor’s reported analyses. They can describe simple differences between posted arm summaries, but they may not reflect the prespecified model or adjustments. The registry record lists no sponsor-reported analyses for those comparisons. The secondary findings also require caution because many outcomes are considered and the record does not report a multiplicity strategy.
Accordingly, the posted primary result supports a description of the estimated within-arm changes and their intervals. It does not, on its own, establish the size, precision, or statistical significance of a difference between the digital intervention and digital control. The record also does not provide enough analysis detail to determine how robust the primary estimates are to alternative modeling choices or missing-data assumptions.
9. Statistical Methods Explained
The primary outcome is reported as a least-squares mean with a 95% confidence interval. The estimates are -3.04 for Arm A and -2.14 for Arm B, in migraine days per month. The intervals are -3.49 to -2.58 and -2.59 to -1.69, respectively. A confidence interval describes the range of values reasonably compatible with an estimate under the statistical model and its assumptions. It is not a guarantee that the true value lies within the interval, and it is not a direct test of the difference between arms.
The registry record does not give a direct primary contrast. Because the arm summaries are model-based estimates, the difference between them cannot be treated as a complete primary analysis: the precision of a contrast depends on the uncertainty and covariance of the estimates, as well as the analysis model. The specific model, adjustment variables, and covariance structure are not reported in the registry record. The record also does not state a primary p-value. Thus, the inferential question of how the assigned groups compare remains incompletely reported.
What do the secondary comparisons represent?
For three continuous secondary outcomes, the posted data include simple recalculations of unadjusted mean differences and associated intervals. These calculations use the arm-level means, standard deviations, and sample sizes recorded for those outcomes. They are descriptive re-calculations from posted summary statistics, not sponsor-reported model results. The registry record lists no reported analyses for these comparisons. The discrepancy indicator is false, so there is no recorded discrepancy requiring the sponsor’s analysis to take precedence; nevertheless, these recalculations should not be mistaken for a prespecified or adjusted analysis.
A p-value describes how incompatible the observed data are with a specified null hypothesis under the assumptions of the test. The unadjusted p-values attached to the recalculated secondary comparisons do not account for the fact that several outcomes are examined. They also do not show the magnitude or practical importance of a difference. The estimated contrast and its interval are needed to describe magnitude and precision; a small p-value alone is not a measure of effect size.
Why can over-dispersion matter?
General statistical context: a count outcome may vary more than a simple model assumes. This is called over-dispersion. If a model underestimates variability, its standard errors can be too small and its intervals too narrow. A model that allows for extra variability can produce more realistic uncertainty estimates. The posted continuous summaries do not report whether over-dispersion was assessed or whether a count-based model was used, so this general issue should not be read as a claim about the trial’s chosen analysis.
How should the planning illustration be read?
The registry includes planning illustrations based on the observed effects, with assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. The rows consider planning for 100%, 75%, and 50% of the observed effect and list participants per arm for 80% power and for 90% power. For example, for the recalculated MMD comparison, the posted planning figures for 80% power are 177, 313, and 705 participants per arm for those effect assumptions, respectively; the figures for 90% power are 236, 419, and 943. These are planning illustrations, not observed power and not evidence of the trial’s original sample-size rationale. The original sample-size justification is not reported in the registry record.
Power is a design-stage probability tied to a specified effect, variability, test, and analysis plan. A post hoc calculation using an observed effect can be especially sensitive to the observed estimate and does not determine whether the trial was adequately designed. The registry record does not report the original target effect, the planned variability, or the assumptions used to choose enrollment. These omissions prevent a reconstruction of the original design calculation from the posted record alone.
More broadly, statistical interpretation depends on the analysis population, missing-data handling, model specification, and multiplicity plan, in addition to the reported estimates. The primary population is identified, but the handling of incomplete outcome data and the details of the primary model are not reported in the registry record. Those missing details limit independent assessment of the analysis assumptions and of how much confidence to place in comparisons across outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The registry record describes a primary endpoint and lists multiple secondary outcomes, including repeated assessments across study timepoints. Examining multiple outcomes can increase the chance of false-positive findings if each is tested without an adjustment or other prespecified strategy. The record does not report a multiplicity plan, such as adjustment of significance thresholds, a hierarchy of hypotheses, or a distinction between confirmatory and exploratory secondary outcomes. The unadjusted secondary p-values should therefore be interpreted cautiously and should not be treated as if they were protected against multiple testing.
The primary analysis population is described as the intent-to-treat population, consisting of randomized participants analyzed according to assigned intervention and recorded in the database. The record does not report how participants with missing Week 12 data were handled, whether an imputation method was used, or whether sensitivity analyses assessed the effect of missing data. It also does not explain why the primary outcome summaries list 266 participants in Arm A and 264 in Arm B, whereas the safety summaries report 278 at risk in each arm. The registry record does not report whether those counts reflect different populations, different data availability, or another reporting convention.
The statistical model used for the primary least-squares means is not described in enough detail to assess the adjustment set, assumptions, or handling of repeated measurements. The direct primary contrast and its uncertainty are also not reported. These omissions matter because conclusions about between-arm differences depend on the analysis plan and on how incomplete observations are addressed.
Interim analyses and any associated adjustments are not reported in the registry record. The record also does not report a sample-size justification or enough prespecified analysis details to determine whether the posted comparisons follow the original plan. In the absence of those details, the safest interpretation is descriptive: consider the arm-specific estimates and the available secondary summaries, while recognizing that the record does not provide the full inferential framework for confirming a between-arm effect.
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 |
|---|---|---|---|
| Arm A | 1 | 278 | 0.4% |
| Arm B | 0 | 278 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A | 0 of 278 |
| Arm B | 0 of 278 |
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 |
|---|---|
| Arm A | 22 of 278 |
| Arm B | 16 of 278 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| peritonsillar abscess | Infections and infestations | 1 of 278 | 0 of 278 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| COVID-19 | Infections and infestations | 2 of 278 | 2 of 278 |
| Sinusitis | Infections and infestations | 2 of 278 | 1 of 278 |
| Influenza | Infections and infestations | 1 of 278 | 1 of 278 |
| Urinary tract infection | Infections and infestations | 0 of 278 | 2 of 278 |
| Migraine | Nervous system disorders | 1 of 278 | 1 of 278 |
| Angina pectoris | Cardiac disorders | 0 of 278 | 1 of 278 |
| Tympanic membrane perforation | Ear and labyrinth disorders | 1 of 278 | 0 of 278 |
| Gastroesophageal reflux disease | Gastrointestinal disorders | 1 of 278 | 0 of 278 |
| Haematochezia | Gastrointestinal disorders | 0 of 278 | 1 of 278 |
| Peripheral swelling | General disorders | 0 of 278 | 1 of 278 |
Serious events with the highest arm-level rate: peritonsillar abscess (0.4%).
The safety summary reports serious adverse events among 278 participants at risk in Arm A and 278 at risk in Arm B. One serious adverse event is recorded for Arm A and zero for Arm B. Deaths are recorded as zero in both groups. The registry lists peritonsillar abscess at 0.4% among the top serious adverse event terms, but the record does not provide further event-level context in the registry record.
Other, non-serious adverse events are recorded for 22 participants in Arm A and 16 in Arm B. These are descriptive counts, not adjusted comparisons. The registry record does not provide a statistical comparison of safety outcomes, information about event severity beyond the serious/non-serious categories, or detail on the timing and relatedness of events. It also does not explain how the safety population relates to the primary outcome population.
Small differences in event counts should not be interpreted as proof of a difference in risk. Safety interpretation depends on event definitions, duration of observation, completeness of reporting, and clinical review, details not reported in the registry record. These figures describe what is recorded in the registry and do not establish a causal relationship between an application and an event.
12. What the Result Does, and Does Not, Mean
The primary outcome summaries indicate that estimated monthly migraine days decreased from baseline in each arm over the assessment interval. The estimates are accompanied by 95% confidence intervals, which express uncertainty around each arm’s least-squares mean under the model used. The registry record does not report enough model detail to assess all assumptions, and it does not report the direct primary comparison between Arm A and Arm B.
That distinction is central. A change observed within an arm is not the same as a difference attributable to the assigned intervention relative to the digital control. Change may reflect several influences, including time, study participation, measurement, and other factors. Randomization can support a between-group comparison when the planned analysis is fully reported, but the arm-specific estimates alone do not quantify that comparison. The missing primary contrast means the posted record does not establish the size or precision of a relative effect.
The secondary outcomes offer additional descriptions, but their unadjusted comparisons are not a substitute for a complete primary analysis. The registry record does not state how multiplicity was addressed, how missing outcome data were handled, or whether the secondary comparisons followed a prespecified hierarchy. These limitations affect how confidently individual secondary findings can be distinguished from chance variation or analysis choices.
The results also do not settle questions beyond the study’s recorded population, applications, and assessment period. The record describes late adolescents and adults with episodic migraine in a virtual randomized study, but does not provide details needed to assess the reach of the findings across settings or participant subgroups. It does not report long-term outcomes beyond the stated study assessments.
Accordingly, the available evidence supports a careful description of the posted arm-level changes and safety counts, not a definitive statement that one digital therapeutic is superior or that either intervention does or does not work. Such conclusions would require complete between-arm estimates, analysis details, and consideration of missing data and multiple outcomes.
13. Why This Trial Matters Statistically
This trial illustrates why an arm-level outcome estimate is not enough to answer a randomized comparison question. The primary endpoint is reported as a least-squares mean change for each assigned group, with a confidence interval for each estimate. But the registry record does not report the primary difference between groups or its uncertainty. The central statistical quantity for comparing randomized interventions is therefore missing from the posted primary results.
The distinction matters beyond this trial. Readers can see that both arm-specific estimates changed in the same direction, but cannot infer the precision of the contrast from those summaries alone. A reported contrast and confidence interval would clarify the range of between-group effects compatible with the analysis. The analysis model and its assumptions would then help readers assess how that estimate was obtained.
The record also illustrates the limits of unadjusted secondary findings. Multiple outcomes can illuminate different aspects of a clinical question, yet testing many outcomes without a reported multiplicity strategy makes isolated p-values harder to interpret. Recalculated comparisons from summary statistics can be useful as transparent descriptive checks, but they should remain distinct from sponsor-reported analyses and prespecified model results.
Finally, design and analysis transparency are part of statistical evidence. Missing details about sample-size justification, missing-data handling, multiplicity, and the primary model prevent a full assessment of how the study’s findings relate to its original plan. The planning illustrations can help readers understand how assumed effect sizes influence sample-size requirements, but they are not observed power and do not reconstruct the original design. The practical statistical lesson is to distinguish reported estimates, recalculated summaries, and unavailable analyses rather than treating them as equivalent forms of evidence.
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 arise from the registry record itself. Most importantly, it does not report a direct between-arm estimate for the primary endpoint, its confidence interval, or a primary p-value. The least-squares mean summaries describe each arm separately, but the primary comparative question remains unanswered in the posted results.
The primary model is not specified. The registry record does not state which covariates were included, whether repeated measurements were modeled, or what assumptions underlie the least-squares means. It also does not report how missing observations were handled or whether sensitivity analyses were conducted. The primary population is defined, but the outcome summary counts and safety at-risk counts differ, and the reason for that difference is not reported in the registry record.
The secondary results have additional limitations. Some between-arm values are unadjusted re-calculations from summary statistics rather than sponsor-reported analyses. The registry lists multiple secondary outcomes and assessment times, but does not report a multiplicity strategy. Several listed outcomes do not have numerical results in the record details. These gaps limit interpretation of the overall secondary evidence and increase the importance of treating individual unadjusted findings as exploratory.
The record does not report a sample-size justification, interim-analysis plan, detailed randomization procedures, or implementation details for masking in the virtual study. It also provides limited information about the applications and digital control condition. Safety results are presented as counts, without a reported comparative analysis or fuller event context. These limitations do not invalidate the recorded summaries, but they restrict independent evaluation of precision, bias, generalizability, and the relationship between the posted results and the trial’s original analysis plan.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Two Digital Therapeutics for the Prevention of Episodic Migraine — NCT05853900.
- Registry record last updated 2025-07-03; status last verified 2025-07.
- Results first posted 2025-07-03.
- 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
NCT05853900 is a completed randomized, double-blind, parallel-group virtual study of two digital therapeutics for episodic migraine prevention in late adolescents and adults. The primary endpoint was change in monthly migraine days from the 28-day run-in period to Week 12. The registry reports arm-specific least-squares mean changes and 95% confidence intervals, but not a direct primary between-arm estimate.
Three secondary continuous outcomes include recalculated unadjusted comparisons based on posted summaries; the registry lists no sponsor-reported analyses for those comparisons. The record does not report the primary model details, missing-data methods, multiplicity plan, or sample-size justification. Safety summaries record one serious adverse event in Arm A and none in Arm B, with zero deaths in both arms. The available information supports descriptive interpretation but leaves important parts of the comparative analysis unresolved.