Leucine for Depression Study (L-DEP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Leucine for Depression Study (L-DEP) (NCT03557684), a randomized early/phase 1 study. The primary outcome is Change in Depressed Mood From Baseline.

2. Clinical Question

This is an experimental study rather than a report of treatment for a clinical population in ordinary care. Its registered focus is whether mood scores change after the study procedures and whether the patterns differ among the treatment combinations. Because the registry record gives no analyzed outcome values, it cannot establish the size, precision, or direction of any between-group difference.

3. Trial Design

The Leucine for Depression Study is registered as an early phase 1, randomized, quadruple-masked, factorial trial sponsored by the University of California, Los Angeles. Its status is terminated. The record lists enrollment of 59. The study began on 2018-09-01, and its primary completion date is 2021-07-31. The reason for termination is not reported in the registry record.

The factorial structure combines an oral treatment factor with an injection factor. Participants could receive oral leucine or oral maltodextrin placebo for 2 weeks, followed by either LPS or intravenous saline. The registry describes leucine as 6 g twice a day and the LPS administration as a single intravenous bolus of 0.8 ng/kg of body weight. The saline comparator is described as a single bolus of 0.9% saline. The record labels masking as quadruple, but does not report which specific people or roles were masked.

The summary describes an initial screening session, an 8-hour session at UCLA Medical Center, and planned telephone follow-up every 3 months for 2 years. It also describes approximately 90 healthy adults as the recruitment plan, while the registered enrollment is 59. The reason the enrollment differs from the approximate recruitment figure is not reported in the registry record. A protocol explaining recruitment, allocation procedures, or the conduct of the study is not reported in the registry record.

The primary outcome was assessed at baseline and at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS or saline administration. Secondary outcomes concern depressive symptoms, social disconnection, fatigue, confusion, and memory and non-memory cognitive domains. The registry lists 15 outcome measures. It does not report the specific statistical model, analysis populations, or handling of repeated measurements.

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: A total of 88 subjects were interviewed, 73 eligible, and 70 randomized. Out of these 70, 11 did not participate in the actual study (7 declined; 3 tested positive in urine toxicology on the study day, which was a pre-set exclusion criterion; 1 reported using a drug given by another study on the study day). Thus, 59 were enrolled in and started the study, an experimental provocation trial involving LPS injection, which was a necessary step for a participant to be considered enrolled and started.

Overall Study

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Change in Depressed Mood From Baseline, measured over At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration.

The primary endpoint is titled Change in Depressed Mood From Baseline. It uses the Depression Subscale of the Short Form of the Profile of Mood States, a score on a scale ranging from 0 to 32. Higher values represent worse outcome, meaning more severe depressed mood. The registry identifies the outcome as continuous and specifies mean and standard deviation as the summary measures.

The measure is intended to capture mood at baseline and during the hours after the study injection. Repeated assessments can describe the time course of mood scores rather than only a single observation. This is relevant to the trial’s experimental question because the study summary describes an acute LPS or saline session following the oral treatment period. That rationale describes the measurement context; it does not establish that the endpoint is valid for every clinical purpose.

There is an important distinction between the endpoint title and its description. Although the title says change from baseline, the description says that absolute values at each time point are presented rather than changes between time points. It also states that zero values in means and standard deviations reflect measured data, not placeholders. The registry record does not report the actual means or standard deviations, so the magnitude and pattern of the recorded scores cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is labeled randomized and quadruple-masked. Randomization is a general design method for assigning participants to study conditions by chance, with the aim of limiting systematic differences between groups at the start. Masking is a general method for reducing the influence of expectations on treatment delivery, participant reporting, or outcome assessment. These labels describe the registered design; the registry record does not report the allocation sequence, concealment procedures, or the particular people whose knowledge of assignment was masked.

What does a factorial design ask?

In general, a factorial design studies more than one intervention factor within the same experiment. In this trial, the factors are oral leucine versus oral maltodextrin placebo and LPS versus intravenous saline. The design can support questions about each factor and about whether their effects vary in combination. A main effect averages across the levels of the other factor, while an interaction asks whether a factor’s association with the outcome depends on the other factor. These interpretations require a specified analysis and appropriate estimates; the design label alone does not show that any particular effect was estimated.

The registry record does not report a statistical model for the repeated mood assessments. In general, repeated scores from the same participant are related rather than independent. An analysis should account for that relationship if it uses multiple time points together. Different modeling choices can estimate change over time, an average difference, or differences at particular assessments, and those choices may answer different questions. No specific choice among these approaches is reported in the registry record.

How should means and standard deviations be read?

For a continuous measure, a mean describes the center of the observed scores, while a standard deviation describes their spread around that center. These are descriptive summaries, not by themselves estimates of a treatment effect. To assess a comparison, readers also need a defined contrast between conditions and an account of uncertainty. The record specifies means and standard deviations for the primary endpoint but does not report their values.

In general, a confidence interval describes a range of values compatible with an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, but it does not prove that an effect is clinically important. A p-value, in general, measures how unusual the observed data would be under a specified null model and its assumptions; it is not the probability that a treatment works. Neither confidence intervals nor p-values for the primary endpoint are reported in the registry record.

What do the planning assumptions mean?

The registry record describes planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not observed trial results. The record does not report the underlying numerical observed effect or the corresponding participant counts for those illustrations. The illustrations therefore cannot be evaluated from the recorded information. They should not be read as observed power or as evidence that the study had a particular probability of detecting an effect.

More generally, a sample-size calculation depends on the effect the design aims to detect, the variability of the outcome, the chosen error rate, allocation, and the analysis method. Planning for a fraction of an observed effect is a hypothetical exercise: it asks what sample size might be needed under stated assumptions if the target effect were smaller than the observed estimate. It does not show that this trial was designed around that target. The trial’s own sample-size justification is not reported in the registry record.

Because the primary measure was assessed repeatedly, a planning calculation based on a simple two-arm comparison may not represent the analysis of all time points or the factorial design. This is a general caution, not a claim about the calculation used for the trial. The registry record does not report whether the planning illustrations account for repeated measures, interactions, or multiple comparisons.

Why does the analysis plan matter?

Statistical interpretation depends on the prespecified outcome definition, comparison, model, and rules for handling incomplete observations. A clear analysis plan helps readers distinguish planned tests from analyses selected after seeing the results. For this trial, the registry identifies the primary outcome and its measurement schedule but does not report the detailed statistical analysis plan. It also lists zero analyses, so there is no registered analysis estimate to interpret. General statistical concepts can explain what an analysis would need to address, but cannot substitute for the missing model or results.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is measured at baseline and at several post-injection times. Looking at multiple times can create multiple opportunities to identify a difference, so an analysis should clarify whether it targets an overall time pattern, a particular time point, or a prespecified contrast. When several comparisons or outcomes are examined, multiplicity procedures may be used to control the chance of misleading findings. These are general statistical considerations, not evidence that any particular procedure was used in this study.

The registry lists secondary outcomes concerning depressive symptoms, social disconnection, fatigue, confusion, memory, and non-memory cognitive function. It reports 15 outcome measures, but does not report a multiplicity strategy, hierarchy among secondary outcomes, or which analyses were considered confirmatory. The registry lists zero analyses. No adjustment method or rationale for not adjusting is reported in the registry record.

Missing-data handling is also not reported in the registry record. The record does not describe how incomplete mood assessments, missed follow-up contacts, withdrawals, or other unavailable measurements were handled. It does not state whether the analysis used all randomized participants, participants who completed the assigned procedures, or another analysis population. The number of participants contributing to each primary outcome time point is not reported in the registry record.

These omissions matter because repeated assessments may be incomplete and because an analysis limited to available observations can differ from one that makes additional assumptions about missing outcomes. Without the analysis population, missing-data method, multiplicity plan, and outcome estimates, readers cannot evaluate the robustness of any primary or secondary finding.

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 5% reporting threshold.

The registry reports serious adverse events, other adverse events, and deaths by study group. For PO Leucine & IV LPS, 23 participants were listed at risk for serious and other adverse events; zero were affected in either category, and deaths were 0. For PO Placebo & IV LPS, the corresponding at-risk count was 18, with zero affected in either category and deaths of 0.

For PO Leucine & IV Placebo, 8 participants were listed at risk for each adverse-event category; zero were affected, and deaths were 0. For PO Placebo & IV Placebo, 10 were listed at risk for each category; zero were affected, and deaths were 0. The record lists no top serious-event terms.

These are the registry’s reported counts, not proof that no symptoms or events of any kind occurred. The record does not provide event definitions, ascertainment details, or further descriptions of non-serious symptoms. The reported counts should be read as the recorded serious and other adverse-event summaries for the stated groups, not as a complete account of the tolerability of the procedures.

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

The record describes a randomized factorial experiment that paired an oral supplement or oral placebo with an LPS or saline injection. It defines depressed mood as the primary outcome and identifies repeated assessment times after the injection. It also records enrollment of 59 and a terminated status. These details characterize the study, but they are not findings about the effect of either intervention.

The registry record does not report numerical primary-outcome results. There are no reported group means, standard deviations, contrasts, confidence intervals, or p-values for depressed mood. As a result, the direction, magnitude, and precision of any difference cannot be determined from the record. It is not appropriate to interpret the absence of results as evidence that the conditions were equivalent or that there was no effect.

The stated outcome title refers to change from baseline, while the outcome description says absolute scores at each time point are presented. That distinction affects interpretation: an absolute score at a follow-up time is not itself a change from baseline. The record does not report an analysis resolving that distinction or specify a primary contrast across the repeated measures.

The safety counts report zero affected participants in the serious and other adverse-event categories for each group, with deaths of 0. Those recorded summaries do not establish the absence of all possible adverse experiences. Likewise, termination does not disclose the reason the study ended, and the record does not say whether it affected the availability or completeness of outcome data.

In short, the registry record supports a careful account of design, measures, enrollment, status, and recorded adverse-event counts. It does not support a claim that leucine improved or worsened mood, or that the intervention had no effect. Nor does it establish how the results would generalize beyond the study population and procedures described in the registry.

13. Why This Trial Matters Statistically

The study is statistically notable for combining two intervention factors in a randomized factorial design while measuring mood repeatedly after an experimental injection. This arrangement raises questions beyond a simple comparison of two groups: the analysis could consider the oral factor, the injection factor, their interaction, and changes over time. Each question needs a clearly defined estimand and analysis. The registry record does not report those analysis details or the resulting estimates.

The endpoint definition also highlights why precise outcome wording matters. The title refers to change from baseline, but the description specifies absolute scores at each assessment. Readers need to know whether the target is a score at a particular time, a change from baseline, or an overall pattern. Without the analysis specification, those interpretations cannot be reconciled from the registry record.

The contrast between the approximate recruitment figure in the summary and registered enrollment also matters for assessing a trial record. The summary describes approximately 90 healthy adults, whereas enrollment is recorded as 59. The reason for the difference is not reported. Enrollment alone does not establish whether the trial met its design goals or whether its estimates would have been precise.

Finally, the record’s terminated status and absence of registered analyses make transparent reporting especially important. Without outcome estimates, analysis populations, missing-data methods, and multiplicity plans, readers cannot judge how much information the study generated or how uncertain its findings would be. These are limitations of the available statistical record, not evidence for or against an intervention effect.

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 registry record has limited information for evaluating the primary outcome. It provides the measure, scale direction, summary-statistic type, and assessment schedule, but no numerical results. It also says that absolute scores, rather than changes between time points, are presented, despite the outcome title referring to change from baseline. The analysis used to address this distinction is not reported in the registry record.

The record identifies a factorial design but does not describe the intended primary contrast, model for repeated observations, or approach to interaction. The allocation procedure and the meaning of quadruple masking in practice are not reported. Without those details, the design labels cannot establish how comparisons were conducted or whether the analysis followed the intended design.

The study is terminated, and registered enrollment is 59, compared with approximately 90 healthy adults in the summary’s recruitment description. The reason for termination and the reason for the difference are not reported in the registry record. The record does not report the number analyzed at each assessment, exclusions, withdrawals, or missing-data handling. It also does not report interim analyses or a sample-size justification.

Secondary outcomes are listed, but their results, analysis plan, and relationship to the primary endpoint are not reported. The record lists 15 outcome measures and zero analyses. It does not report a multiplicity strategy. Consequently, the registry information is not sufficient to assess the completeness of outcome reporting, precision of estimates, or robustness of conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Leucine for Depression Study (L-DEP) — NCT03557684.
• Registry record last updated 2023-06-08; status last verified 2023-06.
• Results first posted 2023-06-08.
• 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 Leucine for Depression Study is registered as an early phase 1, randomized, quadruple-masked factorial trial sponsored by the University of California, Los Angeles. It is marked terminated and lists enrollment of 59. The summary describes approximately 90 healthy adults as the recruitment plan.

The study combines oral leucine or maltodextrin placebo for 2 weeks with LPS or intravenous saline. The primary outcome is depressed mood measured with the Depression Subscale of the Short Form of the Profile of Mood States at baseline and after injection. The outcome description specifies absolute scores at each time point.

The registry lists 15 outcome measures and zero analyses. Numerical primary-outcome results, detailed analysis methods, the reason for termination, and the sample-size justification are not reported in the registry record. The reported adverse-event summaries list zero affected participants in the serious and other categories for each group, and deaths of 0.