The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder (NCT00719706), a randomized phase 2 study. The primary outcome is The 25-Item Hamilton Depression Rating Scale..

2. Clinical Question

This question concerns a comparison between assigned treatment strategies, not whether either group changed over time on its own. A reliable comparison would require the outcome data and the analysis used to estimate the difference between groups, together with its uncertainty. Those results are not reported in the registry record. The trial's planned question can therefore be described, but its answer cannot be determined from the outcome information available in the record.

3. Trial Design

The record describes a randomized, quadruple-masked, parallel-group, placebo-controlled phase 2 trial. It lists enrollment of 40 and a completed status. Randomization is intended to make treatment assignment independent of participants' measured and unmeasured characteristics on average; in an individual trial, it does not guarantee that the groups are identical. The registry record does not describe the randomization sequence or allocation-concealment procedures.

In a parallel-group design, participants are assigned to one study arm and followed under that assignment. The intervention arm received acetyl-L-carnitine plus alpha-lipoic acid, while the comparator arm received placebo. Quadruple masking indicates that the record characterizes the study as masked at four levels, but it does not identify those roles or describe how masking was maintained. Further details are not reported in the registry record.

The trial is identified as phase 2. The record gives a start of 2008-08 and primary completion of 2011-05. Its brief summary describes a 15-week clinical trial. The sponsor is Mclean Hospital. The record does not report the study location, the actual treatment exposure for each participant, adherence, or the timing of any visits other than the primary outcome timeframe.

The intervention is described as an augmentation treatment for participants with an incomplete response to conventional treatments. Details of background treatment, dose adjustment, and whether those treatments were held constant are not reported in the registry record. These details would help clarify which aspects of care differed between arms and how closely the study conditions match its intended clinical question.

The record lists a secondary outcome of phosphorus MRS scans on a 4T scanner, five outcome measures, and no analysis records. The existence of an outcome listing does not establish that numerical results or a comparative analysis are available. Numerical primary-outcome results 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: To limit heterogeneity in the imaging sample, we accepted only type I bipolar disorder participants for the imaging component of the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: At baseline, the number of participants analyzed was the number randomized into the study. At endpoint, the number or participants analyzed is the last observation carried forward of the original 20 participants.

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 The 25-Item Hamilton Depression Rating Scale., measured over Baseline to 15 Weeks.

The primary endpoint is the 25-Item Hamilton Depression Rating Scale, a continuous measure of depressive symptoms. The record describes scores from 0 - 72 units on a scale, with 0 representing the least number of depressive symptoms and 72 representing the most. Its timeframe is Baseline to 15 Weeks.

In general, a symptom scale can make changes in a clinical state more consistently measurable than an unstructured description alone. A continuous score retains information across its range, so an analysis can compare average scores or average changes between randomized groups. Such comparisons need an estimate of the difference and its uncertainty; the registry record does not provide those numerical results for this outcome.

The record specifies a mean as the summary measure and standard deviation as the dispersion measure. In general, the mean describes the center of a set of scores, while the standard deviation describes how spread out individual scores are around that center. Neither statistic, by itself, establishes whether a difference between groups is precise or compatible with chance variation. That assessment ordinarily depends on a comparative estimate and an uncertainty measure, which are not reported in the registry record.

The endpoint is relevant to the stated question because the trial concerns bipolar depression and the scale is described in terms of depressive symptoms. The scale's range and direction help interpret a reported score, but no group scores, changes, or treatment contrast are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details in the registry record are limited. It identifies a randomized parallel-group design and a continuous primary outcome summarized by a mean and standard deviation, but a statistical test, treatment-effect model, confidence interval method, and adjustment strategy are not reported in the registry record. The concepts below are general explanations, not claims about methods used in this trial.

What does randomization contribute?

In general, random assignment supports a fair comparison by making the assigned groups comparable in expectation before treatment begins. It is the assignment process, rather than a statistical adjustment after the fact, that underpins the randomized comparison. Chance imbalances can still occur, particularly in an individual trial. The registry record does not give baseline outcome scores or other group characteristics, so those balances cannot be assessed from the information described.

For a parallel-group trial, a natural target is the contrast between outcomes under the two assigned strategies. Analyses may compare endpoint scores, changes from baseline, or use a model that accounts for baseline scores. Those approaches can differ in assumptions and interpretation. The registry record does not state which approach was used, and it does not report a numerical comparative estimate. No particular test or model should be inferred from the design description alone.

What do the mean and standard deviation convey?

In general, a mean gives a concise description of the center of a continuous outcome, and a standard deviation describes variation among individual observations. Together they help characterize a group, but they do not show how precisely a group mean or a between-group contrast has been estimated. A confidence interval is a range of values compatible with the data under a specified statistical procedure. Its width reflects precision, and its interpretation depends on that procedure and the study design. No confidence interval for the primary comparison is reported in the registry record.

A treatment comparison should be interpreted with both its estimate and uncertainty. A small estimated difference with a wide interval may be compatible with a range of effects; a more precise estimate narrows the values consistent with the data. This is a general principle, not a description of the trial's result. As numerical group results and uncertainty measures are not reported in the registry record, the precision of its primary comparison cannot be described.

What does the scale's direction mean?

The scale is described as ranging from 0 - 72, with lower scores representing fewer depressive symptoms and higher scores representing more. That direction allows readers to interpret a reported score or contrast if one is available. It does not determine the magnitude or importance of a treatment effect. In general, the meaning of a numerical change also depends on the instrument's properties and the clinical context; those interpretive details are not reported in the registry record.

Why does missing-data handling matter?

The record describes endpoint analysis using the last observation carried forward of the original 20 participants. In general, this approach substitutes an earlier observed score when an endpoint score is missing. It keeps the analysis population description tied to the original group, but it relies on an assumption about what the missing endpoint score would have been. If symptoms would have changed after the last observation, carrying the earlier value forward may not represent the unobserved endpoint. The direction and size of any resulting bias depend on why data are missing and how outcomes would otherwise have evolved.

Other missing-data approaches make different assumptions, and sensitivity analyses can examine how conclusions change under alternative assumptions. These are general considerations; the registry record does not report the amount or reasons for missingness, an alternative analysis, or sensitivity analyses. The baseline population description refers to the number randomized, while the endpoint description refers to carried-forward observations. Neither statement supplies the actual number of observed endpoint assessments.

How should planning calculations be read?

In general, a sample-size calculation estimates how many participants per arm would be needed to detect a specified effect under stated assumptions. The planning assumptions described for this trial use a two-sided significance level of 0.05, equal allocation, a normal approximation, and fractions of the observed effect. These calculations are planning illustrations, not observed power, and are not evidence that the study did or did not detect an effect. They also do not establish the trial's original design rationale: the protocol sample-size justification is not reported in the registry record.

A planning estimate depends on the effect used as its target and on its assumptions. If the assumed effect is smaller, the illustration asks what design would be needed to detect a more modest effect; it does not transform the observed trial into a larger one or change the uncertainty of its result. The registry record does not provide the primary-outcome estimate needed to independently assess the effect underlying those illustrations. No numerical planning results should be treated as a trial finding.

Over-dispersion is a general issue for count outcomes when variation exceeds what a simple count model expects; it can make standard errors too small if ignored. The primary endpoint is continuous, not a count outcome, and the registry record does not report a count-model analysis. This concept therefore does not establish anything about the trial's primary analysis. More broadly, a method should be interpreted only when the record identifies that it was used and provides enough detail to understand its assumptions.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and a secondary outcome of phosphorus MRS scans on a 4T scanner. It also records five outcome measures, but does not describe how multiplicity across outcomes, time points, or statistical tests was handled. A multiplicity plan can matter when several comparisons are tested, because considering more tests can increase the chance of at least one apparently unusual result. The record does not report an adjustment strategy or identify a prespecified hierarchy for interpreting multiple outcomes.

The record indicates that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report a single numerical primary comparison or an analysis record; the number of analyses recorded is 0. This limits interpretation: without a clearly reported contrast, result estimate, and method, readers cannot determine which comparison represents the primary test or evaluate its uncertainty. The statistical plan, including any interim analyses or multiplicity procedures, is not reported in the registry record.

For missing data, the endpoint population description specifies last observation carried forward of the original 20 participants. The registry record does not report how many endpoint values were observed, why any values were missing, or how missingness was distributed between arms. It also does not report sensitivity analyses comparing the carried-forward approach with alternatives. In general, missing-data assumptions can affect estimates, so a reported population label alone is not sufficient to assess their impact.

The record says the baseline analyzed number was the number randomized. It does not describe exclusions after randomization, adherence-based populations, or a separate per-protocol analysis. Further detail on analysis populations and the treatment of missing outcomes is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The registry record reports serious adverse-event affected counts of 0 in the ALCAR/ALA arm and 0 in the placebo arm, with 20 at risk in each arm. It lists no serious adverse-event terms. It also reports other adverse-event affected counts of 20 in the ALCAR/ALA arm and 19 in the placebo arm, with 20 at risk in each arm. These are the registry's descriptive counts; they are not a calculated treatment-effect estimate.

The record does not give the specific other adverse events, their severity, timing, duration, or whether investigators judged them related to treatment. Deaths are not reported in the registry record. The affected counts should not be read as evidence about causation or as a complete description of each participant's experience. A zero recorded serious-event count does not, by itself, establish that an intervention has no serious risks, and the counts do not provide a precise comparative safety assessment. Safety interpretation is limited to the reporting available in the registry record.

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

The registry record establishes that a randomized, placebo-controlled phase 2 trial was conducted to investigate acetyl-L-carnitine plus alpha-lipoic acid as augmentation treatment for bipolar depression. It identifies the primary measure as the 25-Item Hamilton Depression Rating Scale, with a baseline-to-15-week timeframe, and describes the endpoint population using last observation carried forward. Those details define the question and some aspects of the planned or recorded outcome handling.

They do not answer whether the combination produced a greater change than placebo. Numerical group outcomes, a comparative estimate, and uncertainty around that estimate are not reported in the registry record. Consequently, neither the direction nor the precision of the primary treatment contrast can be assessed. The absence of an estimate is not evidence that the groups had identical outcomes, just as the completed status is not evidence of a particular result.

Likewise, the safety counts are descriptive. They report no serious adverse events affected in either arm, but the registry does not report the serious-event terms, and deaths are not reported. Other adverse-event affected counts are recorded, but their types and clinical details are not given. Those counts cannot establish that an event was caused by treatment or provide a complete comparison of risk.

In general, conclusions from a randomized trial depend on the observed outcomes, the contrast between randomized groups, the uncertainty of that contrast, and the assumptions behind the analysis. The sample-size illustrations are planning calculations rather than observed power or trial findings. Since the registry record does not report a numerical primary analysis, it cannot support a conclusion about the magnitude, clinical importance, or reliability of a treatment difference.

The appropriate reading is therefore bounded: the record describes a completed trial and its intended comparison, but the reported information is insufficient to determine the primary outcome result. Any stronger statement about benefit, lack of benefit, or comparative safety would go beyond what the registry record reports.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a documented study question and a documented study result. The registry identifies a randomized parallel comparison, a continuous depression scale, and a baseline-to-15-week timeframe. These details allow readers to understand what was intended to be compared. They do not substitute for the outcome data and analysis needed to estimate that comparison.

The record also illustrates why the analysis population and missing-data method matter. It describes endpoint analysis using last observation carried forward of the original 20 participants, but does not report the number with observed endpoint data or the reasons for missing values. In general, a carried-forward value represents an assumption about an unobserved outcome, and different assumptions can affect estimates. Without missingness details or sensitivity analyses, the robustness of an endpoint result would be difficult to assess even if a point estimate were available.

Planning calculations have a separate role. An illustration based on an observed effect and stated assumptions can help researchers think about future study sizes, but it does not describe the precision or power actually achieved by the completed study. It is not a substitute for a reported treatment estimate with uncertainty, and it should not be read as a result of the randomized comparison.

Finally, the registry record lists multiple outcome measures but does not describe how multiple tests or time points were handled. Clear prespecification and reporting of the primary contrast help readers distinguish the main inferential question from secondary or exploratory analyses. Here, the statistical plan and numerical primary comparison are not reported in the registry record. That absence is itself important for interpretation: the study's design can be described, but its primary statistical conclusion cannot be reconstructed from the information recorded.

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 the absence of numerical primary-outcome results. There are no reported arm-level means, standard deviations, changes, comparative estimate, confidence interval, or test result for the 25-Item Hamilton Depression Rating Scale. Without these, neither the direction nor precision of the primary comparison can be evaluated.

Information about analysis methods is also limited. The statistical test or model, handling of baseline scores, and any adjustment strategy are not reported in the registry record. The record says the primary outcome has several categories or time points and was not reduced to one comparison, but does not identify a single numerical contrast. It also does not report a multiplicity plan, interim analyses, or the protocol's sample-size justification.

The endpoint description specifies last observation carried forward of the original 20 participants, but the record does not give the number with observed endpoint measurements or the reasons for missing data. It does not report sensitivity analyses that could show whether conclusions depend on the carried-forward assumption. Details about adherence, treatment exposure, and analysis populations beyond the baseline and endpoint descriptions are also not reported in the registry record.

Further limitations include incomplete information on the masking procedures, randomization process, background treatments, and eligibility criteria. The safety record provides affected counts but does not describe event types or clinical details, and deaths are not reported. These gaps do not prove that the study methods were inadequate; they limit what can be assessed from the registry information alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Use of a Mitochondrial Enhancement Treatment in Bipolar Disorder — NCT00719706.
• Registry record last updated 2012-07-18; status last verified 2012-06.
• Results first posted 2012-07-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed phase 2, randomized, quadruple-masked, parallel-group, placebo-controlled trial sponsored by Mclean Hospital. Enrollment is listed as 40, with a start of 2008-08 and primary completion of 2011-05. The stated question was whether acetyl-L-carnitine plus alpha-lipoic acid, used as augmentation treatment, would outperform placebo for bipolar depression.

The primary outcome was the 25-Item Hamilton Depression Rating Scale from baseline to 15 Weeks. The record describes endpoint analysis using last observation carried forward of the original 20 participants. It records no serious adverse events affected in either arm, other adverse-event affected counts of 20 and 19, and does not report deaths. Numerical primary-outcome results, a comparative analysis, and the statistical plan are not reported in the registry record. The record therefore describes the design and measure but does not permit assessment of the primary treatment effect.