Morning Light Treatment for Traumatic Stress: The Role of Amygdala Reactivity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Morning Light Treatment for Traumatic Stress: The Role of Amygdala Reactivity (NCT04117347), a randomized na study. The primary outcome is Change in Amygdala Reactivity as Measured by Blood-oxygen-level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signal.

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked, parallel-group study of morning light treatment for traumatic stress. It lists stress as the condition and reports enrollment of 50. Participants were assigned to one of three Re-Timer® light therapy regimens: 15, 30, or 60 minutes per day. Because all three groups received a light regimen, the design compares durations rather than comparing light treatment with no treatment. The identity of the person or people masked is not reported in the registry record.

The study status is completed. The record lists a start date of 2020-01-24 and a primary completion date of 2023-03-08. It does not report a study phase beyond “NA”. The sponsor is the University of Michigan. These details describe the registered study, but do not by themselves establish how closely conduct followed the registered plan.

Four participants discontinued after randomization. The reasons and assigned groups are recorded: two in the 30-minute group had no time for the study, one in the 15-minute group had a family emergency, and one in the 60-minute group experienced light-triggered headaches. The primary-outcome description also notes that some participants were not scanned at week 2, with the reason text incomplete in the registry record. Discontinuation and missed scans are distinct issues: a participant could discontinue, miss one measurement, or have other incomplete data. The record does not report the full pattern of outcome availability.

The primary outcome is scheduled at baseline and treatment weeks 2 and 4, with separate left and right amygdala measures. A three-arm, repeated-measure study can raise questions about which group contrasts and time points are primary, how repeated observations are modelled, and how incomplete measurements are handled. Those details, including a statistical analysis plan, are not reported in the registry record. The registry reports four analyses, but does not describe them sufficiently to identify their models or role.

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: Four participants withdrew after study enrollment but before randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Four participants discontinued the study after randomization: 2 no time for study (Light Therapy B group -30 minute), 1 family emergency (Light Therapy A group - 15 minute), 1 light-triggered headaches (Light Therapy C group - 60 minute). Some participants were not scanned at week 2 due to various reasons (e.g. weather, available funding).

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 Change in Amygdala Reactivity as Measured by Blood-oxygen-level-dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Signal, measured over Baseline and treatment week 2 and treatment week 4.

The primary endpoint is change in amygdala reactivity measured by blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging signal. The listed unit is beta weights, and the outcome is described as a mean with standard deviation. During the fMRI scan, participants completed the Emotional Faces Assessment Task. The signal contrast was the average BOLD change during display of negative faces versus display of shapes. The left and right amygdala were assessed separately. Higher values indicate greater amygdala reactivity to negative faces relative to shapes.

Measurements were planned at baseline and treatment weeks 2 and 4. Measuring the same signal over time can describe how it changes during treatment, while comparing assigned groups can address whether changes differ by light duration. The endpoint is a brain-imaging measure of task-related emotional processing; it is not itself a direct measure of symptoms or daily functioning. The registry record does not report numerical endpoint results, group means, changes, uncertainty intervals, or a statistical test for the primary outcome.

General: A task-based BOLD contrast is an indirect measure derived from changes in the fMRI signal during different task conditions. Its interpretation depends on the task, the measurement procedure, and the analysis used. The registry description defines the direction of the measure, but does not establish that any observed change would be clinically important. A clinical-importance threshold is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the outcome as a continuous measure summarized as a mean with standard deviation. It describes four analyses but does not report their models, estimates, or inferential results. The explanations below are general statistical context, not a description of methods confirmed for this study.

What does a mean describe?

General: A mean represents the arithmetic average of measured values in a group. It can provide a concise description of the group’s typical level, but it does not show how individual measurements are distributed. The standard deviation describes variation among measurements around the mean. A standard deviation is not the same as a standard error or a confidence interval: it describes spread in the observations, whereas a confidence interval describes uncertainty about an estimated quantity.

For this outcome, the measure is a BOLD signal contrast expressed in beta weights. A group mean could describe the average contrast at a specified assessment, or the average change over a specified interval, depending on the analysis. The registry record does not report which estimand or contrast underlies its four analyses. It also does not provide numerical means or standard deviations for the primary endpoint.

Why do the contrast and time point matter?

General: A contrast is the specific difference or change an analysis is designed to estimate. Examples in a repeated-measure study might include change from baseline within a group or a difference in change between two groups. These answer different questions. A result at one follow-up does not automatically represent the result at another follow-up, and a result for one measured region does not establish the same pattern in another region.

In this study, the endpoint description identifies baseline, treatment week 2, and treatment week 4, as well as separate left and right amygdala measurements. The registry states that the outcome has several categories or time points and is not reduced to one comparison. It does not specify which time point, region, or between-group contrast is designated as the decisive test. That lack of a single defined comparison makes it especially important not to treat an unspecified result as a complete answer to the research question.

What does a confidence interval convey?

General: A confidence interval gives a range of values compatible with the observed data under a statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval, for the same type of estimate and on the same scale. An interval’s interpretation depends on what quantity it covers, such as a mean change or a difference between groups. It is not a measure of the range containing most individual participants’ values.

No confidence interval for the primary outcome is reported in the registry record. Therefore, the precision of the estimated changes or group contrasts cannot be evaluated. A p-value alone, even if one were reported, would not replace an effect estimate and its uncertainty; the record does not report a primary-outcome p-value either.

Why can repeated observations need special handling?

General: Measurements from the same participant are usually related rather than independent. Statistical methods for repeated observations account for that dependence in some way; treating all observations as independent can misrepresent uncertainty. The specific approach can vary, and the choice may depend on the outcome, the planned contrast, and the pattern of missing measurements.

The outcome schedule contains repeated assessments, but the statistical model is not reported in the registry record. It is not possible to say whether the analyses used a repeated-measures model, a baseline-adjusted model, separate tests at each time point, or another approach. No such choice should be inferred from the fact that four analyses are listed.

What is over-dispersion, and is it relevant?

General: Over-dispersion occurs when observed variability is greater than a statistical model assumes. It is especially a concern for certain count-data models, where an incorrect variance assumption can make uncertainty appear too small. The primary endpoint in this study is described as a continuous mean, not a count. The registry does not report whether over-dispersion was assessed in any analysis, and the available description is insufficient to characterize the four analyses. It would not be appropriate to assume that a particular model or diagnostic was used.

What do the planning assumptions mean?

General: A sample-size planning illustration estimates how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. It is a design calculation, not a result from the completed study and not a measure of the study’s observed power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events; other illustrations use participants per arm.

Those assumptions do not establish the trial’s original design rationale. The record does not report the trial’s own sample-size justification, nor does the information available give numerical planning estimates to interpret. Planning calculations based on an observed effect can be sensitive to how uncertain or unusually large that observed estimate is; they should not be treated as evidence that the study had a particular probability of finding a result.

10. Multiplicity, Missing Data and Analysis Populations

The endpoint includes separate left and right amygdala measurements and assessments at baseline and treatment weeks 2 and 4. In addition, there are three assigned light durations. This creates more than one possible comparison or time-specific result. The registry explicitly notes that the primary outcome has several categories or time points and is not reduced to one comparison. It also lists four analyses without describing their individual purposes or results.

General: When multiple outcomes, time points, regions, or group comparisons are tested, the chance of at least one apparently unusual result can increase if each is interpreted as an independent primary test. A prespecified testing strategy can identify the main comparison or adjust interpretation for multiple tests. The registry record does not report a multiplicity strategy, an analysis hierarchy, or which contrast should be treated as primary. No adjustment method should be assumed.

Missing data also affect interpretation. The registry records four post-randomization discontinuations and notes that some participants were not scanned at week 2. The explanation for those missed scans is incomplete in the record. It does not report the number of missing measurements at each assessment, the availability of week 4 scans, or whether missingness differed by group. The handling of missing data—such as the analysis population, assumptions, or sensitivity analyses—is not reported in the registry record.

General: An analysis that includes only participants with complete measurements can differ from one that uses all available observations or accounts for missing values under stated assumptions. The implications depend on why measurements are missing and on the method used; the fact of a missed scan alone does not determine the direction of any resulting bias. Without a reported missing-data approach and results under that approach, robustness cannot be assessed.

11. 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, other adverse events, and deaths by assigned group. In the 15-minute group, 15 participants were listed as at risk for serious events and 15 for other events; zero serious events, zero other events, and zero deaths were recorded. In the 30-minute group, the corresponding at-risk counts were 15 and 15; the record lists zero serious events, zero other events, and zero deaths. In the 60-minute group, 16 were listed as at risk for each event category; the record lists zero serious events, one other event, and zero deaths.

These are event counts as recorded, not estimates of the primary imaging outcome. The record does not give further details about the one other event in the 60-minute group, such as its description, timing, severity, or relationship to treatment. It also does not report a formal comparison of adverse-event rates. The four discontinuations include one participant in the 60-minute group who stopped because of light-triggered headaches, but the registry’s adverse-event summary does not identify that as a serious event.

General: A zero count in a registry entry means no event was recorded in that category for the listed group; it does not establish that the underlying risk is zero. Event counts should be interpreted alongside the group size, follow-up, event definitions, and completeness of reporting. The available record does not provide all details needed for such an assessment. These safety figures should therefore be read as descriptive registry counts, not as proof of comparative safety or as a substitute for the primary outcome analysis.

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

The registry record establishes that this completed randomized study compared three durations of morning light therapy using the Re-Timer® device and focused on change in task-related amygdala BOLD signal. It specifies a repeated assessment schedule and separate measurements for the left and right amygdala. Those details make the research question identifiable: whether measured amygdala reactivity changed differently across the assigned durations.

The record does not include numerical primary-outcome findings. It therefore does not establish the size or direction of change in any group, whether groups differed, or how precisely any difference was estimated. The absence of those results in the record is not evidence that the groups were equal, and it is not evidence that one duration had a larger effect. No result should be inferred from study completion, enrollment, or the count of analyses.

The endpoint is a fMRI signal contrast elicited during a task involving negative faces and shapes. It represents a particular brain-imaging measure, not a direct measure of every aspect of traumatic stress or emotional processing. The registry defines higher values as greater reactivity for the specified contrast, but does not report a threshold for a meaningful change. Whether a measured difference would matter clinically is therefore not established by the endpoint definition alone.

The recorded discontinuations and missed week-2 scans also matter because the available outcomes may not include every randomized participant at every assessment. The record does not describe the final analysis population or how incomplete data were handled. As a result, the extent to which missing measurements could affect the estimated changes cannot be assessed.

The safety entries document no serious adverse events or deaths in the listed groups and one other adverse event in the 60-minute group. These descriptive counts do not resolve the primary question about amygdala reactivity and do not, on their own, establish a comparative safety profile. In short, the registry identifies the study design and outcomes, but the numerical primary results and enough analysis detail to interpret them are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical questions common to clinical research using repeated biological measurements. Its primary outcome is measured at baseline and two treatment follow-ups, and the left and right amygdala are assessed separately. The scientific question is about differences among three assigned durations, but the registry does not reduce those possibilities to one reported comparison. Making clear which contrast, region, and time point answer the primary question is important for interpreting any eventual estimate.

The study also illustrates the difference between describing a research plan and reporting evidence. A randomized design can support a comparison among assigned groups, but the design label alone does not provide an effect estimate, uncertainty interval, or account of incomplete observations. In this record, four discontinuations and some missed week-2 scans are noted, while the analysis population and missing-data methods are not reported. Those details are essential to understanding what data contribute to a result.

Multiplicity is another relevant issue. Several time points and two separately assessed regions create choices about which results to emphasize. The registry notes multiple categories or time points and lists four analyses, but does not identify their methods or a strategy for interpreting multiple comparisons. This makes transparent reporting of prespecified contrasts and uncertainty especially important.

Finally, planning calculations and observed results answer different questions. The registry describes planning assumptions based on fractions of an observed effect, but such illustrations are not observed power and do not replace the trial’s primary-outcome estimates. A clear report would need to connect the analysis to the assigned groups, specified assessment, handling of incomplete data, and uncertainty around the estimated effect. Without those results, readers can assess the registered question and design but cannot evaluate the primary statistical finding.

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 main limitation for interpreting this trial from the registry record is that numerical primary-outcome results are not reported. The record does not provide the group means, changes, between-group estimates, confidence intervals, or primary-outcome significance tests needed to assess magnitude, direction, or precision. The completed status and the description of the endpoint cannot fill that gap.

The primary outcome is assessed at multiple time points and separately in the left and right amygdala, and the record says it has several categories or time points rather than one reduced comparison. It lists four analyses but does not explain which comparisons they represent, what models were used, or whether any multiplicity strategy was applied. The analysis plan and trial-specific sample-size justification are not reported in the registry record.

Incomplete measurements create a further limitation. Four participants discontinued after randomization, with reasons recorded by group, and some participants were not scanned at week 2. The explanation for missed scans is truncated in the registry record. The number of missing observations at each time point, completeness of week-4 scans, analysis population, and methods for handling missing data are not reported. It is therefore not possible to assess whether missingness could affect estimates.

The registry identifies a single-masked design but does not say who was masked or how masking was maintained. It does not provide further eligibility details or a fuller characterization of the enrolled population. The safety summary also lacks descriptive detail about the one other adverse event in the 60-minute group. These limitations concern what can be learned from the registry record; they do not establish that the study lacked methods or results outside the information recorded there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Morning Light Treatment for Traumatic Stress: The Role of Amygdala Reactivity — NCT04117347.
• Registry record last updated 2024-12-27; status last verified 2024-12.
• Results first posted 2024-03-26.
• 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

NCT04117347 is a completed, randomized, single-masked, parallel-group study sponsored by the University of Michigan. The registry reports enrollment of 50 and lists stress as the condition. The three intervention groups used the Re-Timer® device for 15, 30, or 60 minutes per day. The primary outcome was change in amygdala reactivity measured by BOLD fMRI signal in beta weights during an emotional faces task, assessed at baseline and treatment weeks 2 and 4, with left and right amygdala measurements made separately.

Four participants discontinued after randomization, and some participants were not scanned at week 2. The registry lists no serious adverse events or deaths in any group, and one other adverse event in the 60-minute group. Numerical primary-outcome estimates, analysis methods, multiplicity handling, and missing-data methods are not reported in the registry record. The record therefore describes the question and design but does not allow evaluation of the primary treatment-effect estimates or their precision.