Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing (NCT04650217), a randomized phase 4 study. The primary outcome is Montgomery Asberg Depression Rating Scale (MADRS).

2. Clinical Question

3. Trial Design

The registry describes a phase 4, randomized, quadruple-masked, parallel-group study. Its planned factorial structure combined a drug assignment—L-DOPA or placebo—with a behavioral assignment—exercise training or stretching and toning control. The four named arms were L-DOPA + Exercise, LDOPA + Control, Placebo + Exercise, and Placebo + Control. Each arm description gives a planned N=20, while the study summary describes planned enrollment of 80 adults.

The registry record reports enrollment of 1 and status of terminated. It states that the participant signed consent but was never randomized to a study group. Consistent with that account, the four randomized arms have no reported participants with outcome values. The intended treatment schedule was described as a 12-week duration study, with assessment before and after treatment across cognitive domains, psychiatric symptoms, gait kinematics and mobility, and task-based MRI focused on effort-based decision making and reward processing.

The recorded start date is 2021-10-07 and the recorded primary completion date is 2021-12-31. The record does not explain why the study was terminated, why enrollment stopped, or whether any planned assessment beyond baseline took place. Those reasons and details are not reported in the registry record. The planned randomization and masking describe the intended design; they do not mean that randomized treatment groups were formed in the posted results.

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

Analysis population for the primary outcome, as defined in the registry: 1 participant signed consent to participate in the study but was never randomized to a study group.

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.

Population: 1 participant signed consent for the study but was never randomized into a study group

6. Primary Endpoint

The registry lists the primary outcome as Montgomery Asberg Depression Rating Scale (MADRS), measured over Week 0 (Baseline).

The primary measure is the Montgomery Asberg Depression Rating Scale (MADRS), a rater-administered measure of depression severity. Its total score ranges from a minimum of 0 to a maximum of 60, with higher scores indicating more severe depression. The registry describes the measure as intended to assess changes in depressive symptoms during the study.

Depression severity is relevant to the study's stated focus on mood and mobility problems in late life. A standardized rating scale can give researchers a consistent way to quantify symptom severity and compare measurements over time. That general purpose does not establish that a change was observed in this trial.

The posted timeframe for this primary outcome is Week 0 (Baseline). The only reported MADRS value is 25 for the non-randomized participant; the randomized arms have no posted outcome values. There is no reported post-treatment score or change from baseline. As a result, the available value describes a baseline measurement only and cannot estimate a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a randomized, quadruple-masked, parallel design, but the planned methods must be distinguished from methods actually used to analyze results. Because the participant was never randomized and the registry lists 0 analyses, there is no reported treatment comparison to interpret. The statistical ideas below are general explanations of how such designs and outcomes are commonly considered; they are not a description of an analysis performed for this trial.

What does the factorial design ask?

In general, a 2x2 factorial design evaluates two treatment components together. Here, the planned components were L-DOPA versus placebo and exercise versus stretching and toning control. A factorial analysis can ask about the effect associated with each component, averaged across the levels of the other component, and whether the effect of one component varies according to the other. That latter question is an interaction: it concerns whether the joint pattern differs from what would be expected if the component effects operated independently. No such effects or interaction are estimated in the registry results.

Comparing all four combinations can also be framed as direct contrasts between specific arms. The useful contrast depends on the scientific question and the analysis plan. For example, a comparison that isolates the drug component would need to account for the behavioral assignment, while a comparison of combined treatment with control would answer a different question. The registry record does not report which contrasts were prespecified or how the factorial structure was to be analyzed.

What would repeated measurements contribute?

In general, measuring an outcome at baseline and after treatment makes it possible to describe within-participant change and compare change between assigned groups. An analysis might use follow-up scores adjusted for baseline, model scores over time, or analyze change scores. These approaches rely on their own assumptions and may answer slightly different questions. The registry lists the MADRS timeframe as Week 0 (Baseline), and no follow-up values or change estimates are posted. The record does not state which longitudinal method, if any, was planned.

A confidence interval is a way to convey the uncertainty around an estimate: wider intervals indicate less precision, and intervals that include effects in different directions may leave the direction uncertain. A p-value measures compatibility between data and a specified statistical model under a null hypothesis; it is not a measure of clinical importance. These quantities require an estimable contrast and data. They cannot be recovered from a single baseline score, and none is reported for a randomized comparison.

How should the score be treated?

In general, the MADRS is a bounded score, with possible values from 0 to 60 and higher scores indicating greater severity. A statistical analysis should respect the measurement scale and the distribution of observed scores. A model designed for a continuous outcome may be considered in some settings, but suitability depends on the data and prespecified assumptions. The registry record does not report a model, distributional checks, or other analysis details. With no randomized-arm scores, those choices cannot be evaluated from the posted results.

More generally, over-dispersion occurs when the observed variability is larger than a model assumes. If an outcome is a count, an analysis that accounts for over-dispersion may give more realistic uncertainty than a model that assumes less variability. This is a general statistical concept, not a claim about this trial: the primary measure recorded is a rating-scale score, and the record does not report an over-dispersion assessment or an analysis using a count model.

What do planning assumptions mean?

In general, a sample-size calculation estimates the amount of information needed to detect a prespecified effect under stated assumptions. The registry's planning-illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not proof that a study could detect an effect after data collection. The registry record does not report the trial's own sample-size justification. With no randomized treatment effect posted, the observed-effect basis for a planning illustration is unavailable in the outcome results.

No recalculated treatment estimate is reported. In general, recalculation from summary statistics would be an unadjusted estimate and would not replace a sponsor's own prespecified analysis when the two differ. Here, there is no randomized comparison to recalculate and no reported sponsor analysis to compare against.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when researchers test multiple outcomes, time points, treatment contrasts, or subgroup questions. In general, the more comparisons considered, the greater the chance that at least one result appears notable by chance if no adjustment or prespecified hierarchy is used. Whether an adjustment is appropriate depends on the questions and analysis plan. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or prespecified contrasts.

The record lists 1 outcome measure and 0 secondary outcomes posted. It also lists 0 analyses. This means the available registry entry does not provide a set of estimates across outcomes or contrasts from which to assess multiplicity in practice. It does not establish whether additional analyses were planned or conducted; those details are not reported in the registry record.

Missing-data methods and analysis populations are also not reported in the registry record. The single consenting participant was never randomized, and no randomized-arm outcome values are posted. The recorded MADRS observation is baseline-only and is attributed to the non-randomized participant. The record does not state whether that person had any subsequent measurements or how such measurements, if any, were handled.

In general, an intention-to-treat analysis follows participants according to randomized assignment, while other analysis populations may use different inclusion rules. Because no participant was randomized, no randomized intention-to-treat comparison is available in the posted results. The record does not specify an intended analysis population or missing-data procedure, so neither should be inferred.

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.

The safety record lists the non-randomized participant as at risk for serious and other adverse events. It reports 0 serious adverse events, 0 other adverse events, and 0 deaths for that participant. The four randomized treatment groups each have 0 participants listed at risk in the safety record. Those zero denominators mean that the registry provides no safety experience from randomized participants in those arms.

In general, an adverse-event count needs to be read alongside the number of participants at risk and the duration and completeness of observation. A zero count in a group with no participants at risk is not evidence that the intervention caused no adverse events. A zero count in a very limited record also provides little information about event frequency or uncertainty. The registry does not report an exposure duration for the non-randomized participant or further detail about safety monitoring.

No serious adverse-event terms are listed. The available record therefore reports no events for the one participant represented in the safety denominator, but it does not support comparative safety estimates or conclusions about the planned treatments.

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

The registry record documents a study intended to test L-DOPA and exercise in a randomized 2x2 design, with MADRS as the primary measure. It also documents a major difference between that plan and the posted results: the study is marked terminated, enrollment is 1, and the participant who consented was never randomized. The randomized arms have no MADRS values, and the registry lists 0 analyses.

The MADRS score of 25 is a baseline value for the non-randomized participant. It does not represent a group average, an outcome after treatment, or a contrast between interventions. The record gives no evidence from which to estimate changes in depression symptoms or compare mood, mobility, cognition, or MRI outcomes across the planned arms. No effect size, confidence interval, or significance test for randomized treatment comparisons is reported.

This absence of a comparative result should not be interpreted as evidence that the interventions had no effect, nor as evidence that they had an effect. The trial record does not answer the intended efficacy question. It also does not establish why the study ended, why randomization did not occur, or what the participant's subsequent course was; those details are not reported in the registry record.

For readers, the key distinction is between a study's intended design and the evidence available for analysis. The planned group sizes and treatment schedule describe what researchers proposed to do. The posted enrollment and outcome data describe what is available in the record. Only the latter can support a statistical estimate, and those data do not support randomized treatment-effect estimation.

13. Why This Trial Matters Statistically

This trial is statistically important as an example of why a registered design and a result are not the same thing. A carefully described factorial randomized plan can define useful questions about the separate and combined contributions of a drug and an exercise program. Yet those questions require randomized assignments and outcome information. The registry record reports neither randomized treatment groups with outcome data nor analyses.

The entry also illustrates why denominators matter. Planned arm sizes of N=20 and the stated planned enrollment of 80 do not describe the amount of information available in the posted results. The actual registry enrollment is 1, and that participant was not randomized. Reading the planned sample as if it were an observed study population would misrepresent the evidence.

For statistical interpretation, the record's baseline MADRS value cannot substitute for a treatment contrast. Estimating an effect requires outcome data linked to the relevant assignments, while judging precision requires enough information to characterize uncertainty. Neither is available for the randomized comparisons. A planning illustration cannot fill that gap: planning assumptions are not observed results or observed power.

The record therefore has value for understanding the intended research question and the gap between the design and the posted outcomes, while offering no randomized estimate of treatment effect. That distinction helps prevent both overstatement of a null result and overinterpretation of a baseline observation.

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 trial-specific limitation is that the registry reports termination after 1 participant consented but was never randomized. The planned four-arm comparison therefore has no reported randomized outcome data. Although the MADRS is listed as the primary measure, its posted timeframe is baseline, and the only value belongs to the non-randomized participant. There is no reported follow-up score or change from baseline.

The registry record does not explain the reason for termination, the reason recruitment stopped, or whether any planned study assessments were completed after baseline. It does not report the intended statistical analysis plan, sample-size justification, multiplicity approach, missing-data procedure, analysis populations, or any interim analyses. These details are not reported in the registry record, so conclusions about them would be speculative.

The record names cognitive, psychiatric, gait, mobility, and MRI assessments in the study summary, but it posts no secondary outcomes. It also lists 0 analyses. Consequently, the posted information cannot characterize effects on those other domains or assess whether outcomes were selectively unavailable. The absence of a reported comparison should be understood as unavailable evidence, not a result showing no difference.

The safety entries are also limited: only the non-randomized participant is listed at risk, while the planned randomized groups have no participants listed at risk. The record gives no exposure duration or detailed follow-up information for that participant. Safety counts therefore do not allow comparative estimates or strong conclusions about the planned treatments.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Levodopa and Exercise for Older Adults With Depression and Psychomotor Slowing — NCT04650217.
• Registry record last updated 2023-02-02; status last verified 2023-01.
• Results first posted 2023-02-02.
• 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 describes a phase 4, randomized, quadruple-masked, parallel study of L-DOPA and exercise for older adults with depressive disorder and psychomotor slowing. The planned 2x2 design included L-DOPA or placebo paired with exercise or stretching and toning control; each arm description gives N=20, and the study summary describes enrollment of 80.

The recorded status is terminated, with enrollment of 1. The participant signed consent but was never randomized. MADRS is the primary outcome, with a baseline score of 25 recorded for the non-randomized participant; no randomized-arm MADRS values or analyses are posted. The registry lists 0 secondary outcomes posted. Safety entries report 0 serious adverse events, 0 other adverse events, and 0 deaths for the non-randomized participant, with no randomized participants listed at risk.

The record does not provide a randomized treatment-effect estimate or explain why the study was terminated.