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 Epigenetic Regulation of BDNF in Major Depression (NCT01182103), a registered phase not stated study. The primary outcome is Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01182103 |
| Phase | Phase not stated |
| Condition | Major Depressive Disorder |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 110 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Chang Gung Memorial Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled people with Major Depressive Disorder and healthy subjects. The registry lists enrollment of 110. For the primary methylation analysis, only 39 out of the 48 MDD patients provided enough blood sample for analysis; the corresponding number of healthy subjects contributing data is not reported in the registry record.
Intervention
No treatment assignment or intervention is described for the comparison of MDD patients with healthy subjects. The registry summary also describes aims involving depressive symptoms, suicidal behavior, antidepressant responses, blood BDNF protein and RNA, and BDNF rs6265 gene, but does not report detailed procedures for these investigations.
Comparator
Healthy subjects are the stated comparison group for the primary outcome, which concerns BDNF DNA methylation. The registry record does not provide detailed eligibility criteria or explain how participants entered either group. Allocation is not stated, and the groups are not a like-for-like randomized control comparison.
Primary question
The primary question is how BDNF DNA methylation in MDD patients compares with methylation in healthy controls. The measure is the averaged percentage of methylation at each listed CpG site. The numerical group estimates, their uncertainty, and the statistical tests for this comparison are not reported in the registry record.
3. Trial Design
The registry record describes a study titled “Epigenetic Regulation of BDNF in Major Depression,” sponsored by Chang Gung Memorial Hospital. Its listed condition is Major Depressive Disorder, and its enrollment is 110. The record gives a start date of 2010-08 and a primary completion date of 2012-07; the status is COMPLETED.
The two listed groups are Major depressive patients and Healthy subjects. The primary outcome compares BDNF DNA methylation between MDD patients and healthy controls. The registry summary also describes aims concerning methylation, histone modification, depressive symptoms, suicidal behavior, antidepressant responses, and associations between blood BDNF protein and RNA and BDNF rs6265 gene. A secondary outcome concerns BDNF levels in MDD patients before and after treatment and in healthy controls. Detailed treatment procedures and the timing of measurements for these aims are not reported in the registry record.
This is not a randomized comparison: allocation is not stated, and the groups are not a like-for-like control comparison. The arm descriptions do not provide further details. Consequently, the comparison should be read as a comparison between the listed patient and healthy-subject groups, not as an estimate of the effect of assigning a treatment. Eligibility criteria, recruitment procedures, blinding, and the approach to group comparability are not reported in the registry record.
The primary outcome has a timeframe of 2 years. The registry specifies a mean and standard deviation for a continuous measure, with units of percent. It states that only 39 out of the 48 MDD patients provided enough blood sample for this analysis. The number of healthy subjects with usable primary-outcome data, and the reasons other participants did not contribute data, 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.
Overall Study
| Stage | Major Depressive Patients | Healthy Subjects |
|---|---|---|
| STARTED | 48 | 62 |
| COMPLETED | 48 | 62 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Only 39 out of the 48 MDD patients provided enough blood sample for this analysis.
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 | Major Depressive Patients | Healthy Subjects | Total |
|---|---|---|---|---|
| Participants analysed | 48 | 62 | 110 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 48 | 62 | 110 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 42.44 (SD 12.09) | 30.18 (SD 5.6) | 35.53 (SD 10.81) |
| Sex: Female, Male: Female | Participants | 32 | 38 | 70 |
| Sex: Female, Male: Male | Participants | 16 | 24 | 40 |
| Region of Enrollment: Taiwan | participants | 48 | 62 | 110 |
6. Primary Endpoint
The registry lists the primary outcome as Brain-derived Neurotrophic Factor (BDNF) DNA Methylation of Major Depressive Disorder (MDD) Patients and Healthy Controls, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percent |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is BDNF DNA methylation in MDD patients and healthy controls. It is described as the averaged percentage of methylation at each CpG site listed, with the outcome expressed in percent. The registry identifies the summary measure as a mean and the measure of dispersion as a standard deviation. Its timeframe is 2 years.
In general, DNA methylation is an epigenetic measure, and a percentage summarizes the methylation measurement at a specified site. Reporting results by CpG site matters because an average at one site need not describe methylation at another. The stated outcome therefore refers to site-specific measurements rather than a single overall percentage across all sites.
The study summary frames BDNF methylation as relevant to its investigation of epigenetic regulation in MDD, including possible relationships with depressive symptoms, suicidal behavior, and antidepressant responses. In general, an outcome can help describe a biological characteristic and its association with group membership or other measured features. A group comparison alone does not establish that methylation causes a condition or that changing methylation would change symptoms.
The registry record does not report the numerical means, standard deviations, group differences, confidence intervals, or tests for the primary endpoint. It also does not report the specific CpG-site estimates in the available record. Thus, the endpoint definition can be identified, but its observed magnitude and precision cannot be evaluated from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a biologically focused comparison: BDNF DNA methylation in MDD patients and healthy controls. It defines the measure as the averaged percentage of methylation at each CpG site listed and specifies mean and standard deviation summaries. However, the numerical results for this endpoint are not reported in the registry record. There is therefore no posted estimate of the methylation level in either group, no estimate of the difference between groups, and no measure of uncertainty for that difference.
This absence of numerical outcome estimates is central to interpretation. The registry record cannot establish whether the groups had similar or different methylation values, how large any observed separation was, or how precisely it was estimated. It also does not report the statistical test, confidence interval, or p-value for the primary comparison. A conclusion about the direction or statistical strength of a group difference would require information that is not reported in the registry record.
The analysis population is also important. The record states that only 39 out of the 48 MDD patients provided enough blood sample for the primary analysis. This means that the primary endpoint is not described as available for every MDD patient in the listed group. The number of healthy subjects with usable blood samples is not reported in the registry record. Without the outcome results and complete analysis counts, readers cannot assess how much data contributed to each group summary or whether the analyzed participants differed from those without usable samples.
In general, a mean describes the center of a continuous outcome, while a standard deviation describes variability among measurements. Neither summary alone expresses the uncertainty in a group comparison. A confidence interval is a range of values compatible with the data and analysis assumptions; it can help readers judge the precision of an estimated difference. No such interval is reported for this endpoint, so precision cannot be assessed from the registry record.
The comparison is not randomized, and allocation is not stated. The groups are not a like-for-like control comparison. Therefore, even if numerical differences were available, a group contrast would be descriptive and would not by itself show that MDD caused a methylation difference, or that methylation caused MDD. Other differences between the groups could contribute to a measured association. The registry record does not report adjusted estimates or the variables used in any adjustment.
The registry summary lists broader aims involving histone modification, depressive symptoms, suicidal behavior, antidepressant responses, and blood BDNF protein and RNA. The posted results do not provide numerical findings for these aims in the information recorded. The secondary outcome title refers to BDNF levels before and after treatment and healthy controls, but its detailed estimates and analysis are not reported in the registry record. Accordingly, the record describes the scientific questions and endpoint, but does not permit a quantitative assessment of the findings.
9. Statistical Methods Explained
The registry describes a continuous primary outcome, summarized by a mean and standard deviation. The outcome is the averaged percentage of methylation at each listed CpG site. The record specifies a 2 years timeframe and says that only 39 out of the 48 MDD patients provided enough blood sample for the primary analysis. It does not report the numerical outcome values or the statistical procedures used to compare the groups.
What does a mean describe?
In general, the mean is a measure of the center of a set of continuous observations. For an outcome expressed as a percentage, it gives an average methylation value for the measurements summarized. A mean is useful for describing a group, but it does not show the full distribution of values. Different distributions can have the same mean, and measurements within a group can vary substantially around that mean.
The standard deviation is a descriptive measure of that variation. It describes how spread out individual measurements are around the mean, under the usual interpretation of this summary. It is not the same as the standard error, which concerns uncertainty in an estimated mean, and it is not a confidence interval for the difference between groups. The registry identifies standard deviation as the dispersion measure but does not provide its numerical values.
Why does the site-level definition matter?
The endpoint refers to methylation at each CpG site listed. In general, measurements at separate sites can have different values and patterns. A site-specific estimate should therefore be interpreted as an estimate for that site, rather than as a universal summary of BDNF methylation. The registry record does not provide the individual site results or explain how the listed sites were selected.
When more than one site or outcome is examined, multiple comparisons can arise. In general, conducting several tests creates more opportunities for apparently notable findings by chance if each test is considered separately. Researchers may use prespecified primary outcomes, adjustment methods, or other strategies to address multiplicity. The registry record does not report whether a multiplicity strategy was planned or used, nor does it state which specific analyses correspond to the listed count of 3 analyses.
What can a group comparison establish?
In general, a comparison of means estimates how the average outcome differs between groups. A confidence interval, when reported, communicates uncertainty around an estimated contrast under the analysis assumptions. A p-value, when reported, measures how compatible the observed data are with a specified null model; it is not a measure of the size or importance of an effect. The registry record does not report a mean difference, confidence interval, p-value, or the test used for the primary comparison.
The groups are MDD patients and healthy subjects, and the record says this is not a randomized comparison. In general, randomization can help balance both measured and unmeasured characteristics between treatment groups. Without random allocation, group differences may reflect other characteristics as well as the condition under study. This matters for causal interpretation: an unadjusted association cannot by itself identify a causal effect. The registry record does not report whether estimates were adjusted or which covariates, if any, were considered.
How should sample-size illustrations be read?
The registry record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The illustrations consider effects stated as fractions of the observed effect. For non-time-to-event outcomes, the figures are participants per arm; time-to-event illustrations instead give total events using the Schoenfeld method. These are planning calculations, not counts of participants actually analyzed and not proof that the study had a particular probability of detecting an effect.
In general, such an illustration depends on its assumptions, including the effect chosen for planning, variability, significance threshold, and allocation. If an observed estimate is uncertain, basing planning on it can also make the illustration uncertain. The actual numeric planning values and the observed effect on which they are based are not reported in the registry record, so no particular sample-size target or power conclusion can be evaluated.
Over-dispersion is a general concern when variability is greater than an analysis model assumes. In general, if a model understates variability, standard errors may be too small and uncertainty may appear narrower than it should. The record does not state that over-dispersion was assessed or that a model requiring such an assessment was used. No specific distributional assumptions for the primary methylation analysis are reported in the registry record.
Finally, the analysis sample is not necessarily the same as the enrollment. The record explicitly notes that 39 out of 48 MDD patients had sufficient blood for the primary analysis. In general, missing outcome data can reduce precision and can also introduce bias if the availability of measurements is related to the outcome or participant characteristics. The missingness mechanism and the handling of unavailable samples are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures and 3 analyses. Its summary describes several related scientific aims, including methylation, histone modification, depressive symptoms, suicidal behavior, antidepressant responses, and relationships involving blood BDNF protein, RNA, and BDNF rs6265 gene. The primary outcome concerns methylation at listed CpG sites, and a secondary outcome concerns BDNF levels before and after treatment and in healthy controls. The registry record does not report how these outcomes and analyses were prioritized beyond identifying the primary outcome.
When a study examines multiple outcomes, sites, or comparisons, multiplicity can affect how individual statistical findings should be interpreted. In general, prespecifying a primary question and explaining any adjustment for multiple testing helps readers distinguish confirmatory analyses from exploratory ones. Whether multiplicity adjustments were planned or applied is not reported in the registry record. Numerical results and p-values for the listed outcome measures are also not reported there.
For the primary outcome, only 39 out of the 48 MDD patients provided enough blood sample for analysis. The registry record does not state why the other MDD patients lacked sufficient samples, whether sample availability was associated with participant characteristics, or how unavailable measurements were handled. The number of healthy subjects with usable primary-outcome data is not reported in the registry record. It also does not describe an imputation procedure or another method for addressing missing outcome data.
In general, missingness matters because the observed participants may not represent everyone enrolled. If measurements are missing for reasons related to the outcome or to participant characteristics, a complete-case summary can differ from the result that would have been obtained with complete data. The registry record does not report the assumptions used about missingness, the population included in each analysis, or sensitivity analyses addressing missing data.
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 |
|---|---|---|---|
| Major Depressive Patients | 0 | 48 | 0.0% |
| Healthy Subjects | 0 | 62 | 0.0% |
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 |
|---|---|
| Major Depressive Patients | 0 of 48 |
| Healthy Subjects | 0 of 62 |
The registry lists 48 Major Depressive Patients and 62 Healthy Subjects as at risk for serious adverse events, and 0 affected in each group. It also lists 48 and 62, respectively, as at risk for other adverse events, with 0 affected in each group. These figures describe the adverse-event entries in the registry; they do not provide detailed event narratives or definitions.
The deaths fields are recorded as null for both groups. A null entry is not the same as a reported count of 0, so the death information should be treated as not reported in the registry record rather than as evidence that no deaths occurred. The registry lists no top serious adverse-event terms.
In general, adverse-event counts are interpreted in light of how events were defined, collected, and attributed, and in relation to the period of observation. The registry record does not report these details or a fuller safety analysis. The listed figures should therefore be read narrowly: no affected participants are entered for serious or other adverse events in the stated groups, while the death fields are unspecified.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study examined BDNF DNA methylation in MDD patients and healthy controls, and that it defined the primary outcome as the averaged percentage of methylation at each listed CpG site. It also records a 2 years timeframe and specifies mean and standard deviation summaries. These details identify the measurement and the intended group comparison, but they do not communicate the observed result.
The numerical primary-outcome estimates are not reported in the registry record. Without group means, standard deviations, an estimated contrast, or an uncertainty interval, readers cannot determine the direction, size, variability, or precision of any difference. The record also does not report the inferential test or p-value for this comparison. No conclusion about whether methylation values were higher, lower, or similar between groups can be drawn from the recorded information.
Even if an association were reported, the comparison is not randomized and allocation is not stated. In general, a nonrandomized group comparison can identify a relationship in the measured data, but cannot by itself show that group status caused a biological difference. Nor can it show that the biological measure caused symptoms or clinical outcomes. Other characteristics of participants may also be related to the observed values.
The registry summary describes interests in depressive symptoms, suicidal behavior, antidepressant responses, histone modification, and BDNF protein and RNA. These aims should not be mistaken for established findings. Detailed numerical results for them are not reported in the registry record. Similarly, the secondary outcome title refers to BDNF levels before and after treatment and healthy controls, but the title alone does not provide an estimated change or a comparison.
The study therefore contributes a defined research question and a record of the planned biological measurement, but the information recorded does not support a quantitative judgment of its findings. It also does not establish a treatment effect, a causal mechanism, or clinical benefit. Those questions require relevant outcome results and an analysis that supports the specific inference being made.
13. Why This Trial Matters Statistically
This study is statistically notable for the way it connects a clinical group comparison with a biological measurement. Its primary endpoint is not a symptom score or a treatment response, but a continuous methylation measure expressed as the averaged percentage at each listed CpG site. Understanding this definition is necessary before interpreting any result: estimates at separate sites may address separate biological features, and their values should not automatically be treated as interchangeable.
The record also highlights the importance of separating enrollment from the analysis population. It lists enrollment of 110, while only 39 out of the 48 MDD patients are stated to have provided enough blood for the primary analysis. The number of healthy subjects included in that analysis is not reported in the registry record. In general, this distinction affects both precision and the possibility that the analyzed participants differ from those without usable measurements.
Another statistical issue is the nonrandomized nature of the group comparison. MDD patients and healthy subjects are not treatment groups created through random allocation, and the registry does not describe allocation. A difference between groups would therefore be an association rather than, by itself, a causal estimate. This distinction is especially important when a biological outcome is considered alongside symptoms or treatment response.
Finally, the registry describes multiple related aims and lists 3 outcome measures and 3 analyses, while leaving multiplicity procedures and numerical results unreported. Readers need both a clear account of which analyses address the primary question and estimates with measures of uncertainty to assess evidence. The record supplies the endpoint framework, but it does not report the numerical findings needed to judge magnitude or precision.
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.
A key limitation of the registry record is that it does not report numerical results for the primary methylation endpoint. No group means, standard deviations, estimated differences, confidence intervals, or p-values are recorded. The endpoint can be described, but its observed pattern and precision cannot be assessed.
The primary analysis includes only MDD patients who provided enough blood sample: 39 out of the 48 patients in that group. Reasons for insufficient samples and the handling of missing measurements are not reported in the registry record. The number of healthy subjects contributing usable primary-outcome data is also not reported, which limits assessment of the analysis population and the balance of available data.
The comparison is not randomized, allocation is not stated, and the arms are not a like-for-like control comparison. Detailed eligibility criteria, recruitment methods, participant characteristics, and any adjustment for group differences are not reported in the registry record. These omissions limit the ability to evaluate comparability and to interpret any group association causally.
The outcome is described for each listed CpG site, but site-level estimates and the rationale for site selection are not reported in the registry record. The record also does not explain how it handled the related aims and multiple outcomes, whether any multiplicity adjustment was used, or which analysis corresponded to each listed outcome. Detailed procedures for the secondary outcome and its before-and-after-treatment comparison are not reported either.
Finally, the adverse-event entries do not provide event definitions or collection details, and the death fields are null. These safety entries therefore have limited interpretive detail. Overall, the registry record documents the study question and some aspects of its measurement, but leaves important analytical, missing-data, and outcome-result information unreported.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Epigenetic Regulation of BDNF in Major Depression — NCT01182103.
- Registry record last updated 2014-08-15; status last verified 2014-07.
- Results first posted 2014-08-15.
- 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
NCT01182103, “Epigenetic Regulation of BDNF in Major Depression,” is listed as COMPLETED and was sponsored by Chang Gung Memorial Hospital. The record gives enrollment of 110, a start date of 2010-08, and a primary completion date of 2012-07. Its listed condition is Major Depressive Disorder.
The primary outcome is BDNF DNA methylation in MDD patients and healthy controls, measured as the averaged percentage of methylation at each listed CpG site. The record specifies mean and standard deviation summaries and a 2 years timeframe. It states that only 39 out of the 48 MDD patients provided enough blood sample for this analysis.
The registry summary describes related aims involving epigenetic measures, symptoms, suicidal behavior, antidepressant responses, and blood BDNF measures. Numerical primary and secondary outcome results, analysis details, and the number of healthy subjects included in the primary analysis are not reported in the registry record.