LIFUP for Treatment of Motor Deficits in Parkinson's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LIFUP for Treatment of Motor Deficits in Parkinson's Disease (NCT04593875), a randomized na study. The primary outcome is Motor Assessment 1: Unified Parkinson Disease Rating Scale (UPDRS) Section 3.

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked crossover study of active and sham LIFUP for motor deficits in Parkinson’s disease. The registry record lists an enrollment of 31 and marks the study as completed. The listed start date is 2022-06-15, and the primary completion date is 2024-07-24. The study is recorded as having no applicable phase.

The two sequences were active LIFUP followed by sham LIFUP, and sham LIFUP followed by active LIFUP. Active LIFUP was directed to the internal globus pallidus while participants were in an MRI scanner. The descriptions state that the second session occurred 2 weeks after the first. They do not specify additional details about session procedures, adherence, or whether every enrolled participant completed both sessions.

Randomization of sequence can help balance the order in which active and sham sessions occur. Masking is intended to limit the influence of treatment knowledge on participants’ experiences or study assessments. The record identifies the study as triple-masked, but does not identify which roles were masked or explain how masking was maintained. These details are not reported in the registry record.

The primary motor assessment was scheduled pre- and post-LIFUP at Day 1 and Day 15. The registry also lists outcomes concerning BOLD fMRI signal during on versus off blocks and perfusion in the internal globus pallidus, external globus pallidus, and putamen. The record names six outcome measures overall, but does not provide an analysis plan explaining how the repeated measurements, treatment sequence, or multiple outcomes were handled.

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.

First Intervention (1 day)

Washout / Follow-Up (2 weeks)

Reasons for not completing this period:

Second Intervention (1 day)

Second Intervention Follow-Up (1 week)

Analysis population for the primary outcome, as defined in the registry: One participant was not included in motor symptom analyses due to extreme motor symptom fluctuations at baseline confounding measurement of LIFUP-related changes

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: One participant in the "sham then active" group was withdrawn after their first in-person session due to excessive head motion in the MRI.

6. Primary Endpoint

The registry lists the primary outcome as Motor Assessment 1: Unified Parkinson Disease Rating Scale (UPDRS) Section 3, measured over Pre-LIFUP and Post-LIFUP at Day 1 and Day 15.

The primary endpoint was Motor Assessment 1: the Unified Parkinson Disease Rating Scale (UPDRS) Section 3. It is an 18-item assessment of motor function, including tremor, bradykinesia, and gait. The total score ranges from 0 to 108 points, with higher scores indicating greater severity. The registry identifies the endpoint as a mean and describes standard deviation as its dispersion measure.

A structured motor assessment gives researchers a consistent way to describe motor symptoms and compare scores across assessment times or treatment conditions. Reporting a mean can convey the average score in a group or condition, while a standard deviation describes how spread out individual scores are around that mean. These summaries do not, by themselves, show whether an observed difference is attributable to treatment or how precisely it has been estimated.

The outcome was scheduled before and after LIFUP at Day 1 and Day 15. That repeated schedule is relevant to interpreting a crossover study, because scores may be considered in relation to both treatment and assessment time. The registry record does not report the resulting means, standard deviations, treatment contrast, or uncertainty around a contrast. It also does not state how scores across the listed time points were combined for a primary comparison. The outcome definition therefore explains what was intended to be measured, but not what the measurements showed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design mean?

In a crossover study, participants are assigned to treatment sequences and may receive more than one condition at different times. Here, the registry describes an active-then-sham sequence and a sham-then-active sequence, with the second session 2 weeks after the first. This design can allow comparisons that account for stable differences between participants, because a participant may contribute observations under both conditions. That is general statistical context; the registry record does not report whether the analysis used within-participant comparisons.

Order and time matter in crossover studies. Symptoms can change over time, and the experience of one condition could potentially influence a later measurement. A suitable analysis may therefore need to consider treatment, period, sequence, and the relationship between repeated observations. These are general design considerations, not descriptions of an analysis reported for this study. The registry record does not state whether these factors were evaluated or how they were modeled.

What do randomization and masking contribute?

Random assignment to treatment sequence is intended to reduce systematic differences between sequence groups. It does not guarantee that all relevant factors will be balanced, especially in a study with limited enrollment, and it does not replace reporting the analysis. The record labels the study randomized and triple-masked. It does not specify which people were masked, how treatment assignments were concealed, or whether masking was assessed.

Masking can reduce the risk that knowledge of treatment assignment influences behavior, assessment, or interpretation. Its effectiveness depends on how the intervention and sham are experienced and how procedures are conducted. The registry provides no further information about those details, so the masking label should be read as a design description rather than proof that expectations could not affect measurements.

How should the continuous outcome be understood?

The registry identifies the primary endpoint as a continuous score summarized by a mean, with standard deviation as the dispersion measure. A mean describes the central average of observed scores. A standard deviation describes variation among scores around that average; it is not the same as the uncertainty in the mean or in a difference between conditions. General statistical interpretation would also consider an effect estimate and an uncertainty interval, but those results are not reported in the registry record.

Repeated UPDRS assessments were scheduled before and after LIFUP at Day 1 and Day 15. Measurements from the same participant are generally related rather than independent. Analyses of repeated data may need to account for that relationship. The record does not report whether the analysis used a paired method, a repeated-measures model, or another approach. It also does not report the outcome values needed to recalculate an unadjusted comparison.

What does the planning description mean?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such sample-size illustrations are planning exercises: they describe the number of participants per arm that would be needed under the stated assumptions and a chosen target for power. They are not observed power and do not show that an effect was detected in this completed study. The record does not give numeric planning results or the fraction values in the registry record for this interpretation.

General statistical context: a normal approximation relies on assumptions about the sampling distribution and may be less suitable when data are sparse or strongly irregular. In event-count analyses, over-dispersion means that observed variability exceeds what a simple model assumes; accounting for it can affect uncertainty estimates. The registry does not report such an analysis for the primary motor score, and these general concepts should not be mistaken for methods used in this trial.

What information is needed to interpret an analysis?

Useful reporting would identify the estimand or comparison of interest, the analysis population, how repeated time points were handled, the effect estimate, and a measure of uncertainty. A statistical plan would also clarify whether models adjusted for sequence or period and how missing data were treated. Those details are not reported in the registry record. Without them and without numerical endpoint results, the statistical design can be described, but a treatment-effect analysis cannot be reconstructed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary motor assessment and secondary outcomes concerning BOLD fMRI signal during on versus off blocks and perfusion changes in the internal globus pallidus, external globus pallidus, and putamen. It also identifies multiple categories or time points for the primary outcome and states that these were not reduced to one comparison. The record lists zero analyses.

When a study examines multiple outcomes, time points, or contrasts, the chance of at least one apparently notable result can increase if each is assessed separately. Statistical approaches to multiplicity can define a primary comparison in advance, adjust inference across a family of tests, or clearly distinguish confirmatory from exploratory analyses. This is general statistical context; the registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a statistical analysis plan.

The UPDRS Section 3 assessment was scheduled before and after treatment at Day 1 and Day 15. The record does not specify which of those measurements formed the main treatment contrast, whether all were analyzed, or how their dependence was handled. Without the analysis population, participant-level outcome data, and a stated plan for missing measurements, it is also not possible to assess the effect of missing data on the reported outcome. The record identifies one participant excluded from motor symptom analyses because of extreme baseline fluctuations, but does not describe other missingness or the handling of that exclusion in an analysis.

These reporting gaps limit interpretation; they do not establish that a particular multiplicity or missing-data method was or was not used outside the registry record.

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 separately for active and sham LIFUP sessions. For the Active LIFUP Session, 30 were at risk and 0 serious adverse events were reported. For the Sham LIFUP Session, 31 were at risk and 0 serious adverse events were reported. Deaths are listed as 0 in both groups. These are the safety counts in the registry record.

The record also reports other adverse events: 5 among 30 at risk in the Active LIFUP Session group and 6 among 31 at risk in the Sham LIFUP Session group. The registry does not provide the event terms or severity details in the registry record. The other-event counts should not be confused with serious adverse events; they are presented as a separate category.

In a crossover study, participants may contribute observations during more than one session. The group counts are described by session, and the record does not clarify how to interpret them as participant-level risks or whether the same individuals contributed to both groups. They should therefore be read as the posted session-group figures, not as a basis for calculating a comparative risk. Zero reported serious events is not proof that no risk exists, especially without details on event definitions, follow-up, and ascertainment.

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

The registry record establishes the study’s design, intended motor endpoint, assessment schedule, and posted safety counts. It does not report a numerical comparison of active and sham LIFUP on UPDRS Section 3. There is therefore no basis in this record for describing the direction or magnitude of a motor-score difference, its precision, or its statistical significance.

The study description frames LIFUP as a feasibility investigation and explains that MRI-compatible delivery can be used to observe brain activity, blood flow, and connectivity. The registry lists secondary outcomes related to BOLD fMRI signal and perfusion. These aims describe what the study examined; they are not evidence that a particular brain or motor effect occurred. No numerical outcome results for those measures are reported in the record details.

The primary scale is intended to measure motor function, with higher scores indicating greater severity. That scoring direction helps explain what a score would mean, but no observed scores or changes are reported. A planned assessment at more than one time point cannot substitute for the actual measurements or the analysis used to compare conditions.

The safety counts provide a limited description of events recorded by session group. They do not establish the overall safety profile, and the other adverse event terms and details are not reported in the registry record. Similarly, the fact that the study is marked completed does not itself indicate whether the intervention had a beneficial, harmful, or null effect.

In practical terms, the record supports a description of the research question and design, not a conclusion about treatment efficacy. A reader would need posted outcome estimates, uncertainty measures, and details of the analysis population and methods to judge what the observed data show. No medical recommendation follows from the information.

13. Why This Trial Matters Statistically

This study raises statistical issues that are common in early clinical research: interpreting repeated measurements, accounting for treatment order, defining a primary contrast, and separating feasibility questions from evidence about treatment effects. The randomized crossover structure can be informative because the design assigns participants to different treatment sequences. At the same time, valid interpretation depends on how within-participant observations and time effects are handled.

The primary endpoint is a structured motor score, and the registry specifies its direction, range, and assessment schedule. Those details help readers understand the planned measurement. But endpoint definition and study completion are not substitutes for results. The registry lists zero analyses and does not report the outcome estimates needed to evaluate either the size or precision of a motor-score comparison.

The record also makes visible an analysis-population decision: one participant was excluded from motor symptom analyses because extreme baseline fluctuations confounded measurement of LIFUP-related changes. Transparent reporting of such decisions matters because exclusions can affect how well an analysis represents the enrolled group. The registry does not give enough information to assess the effect of this exclusion or to determine how other missing measurements were treated.

Finally, the separate safety counts illustrate why event categories and denominators must be read carefully, especially in a crossover design where a participant may have more than one session. Statistical interpretation requires clear definitions, an explicit comparison, and uncertainty estimates. Without reported endpoint results and analysis details, the design can be described, but its findings cannot be quantified.

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 of the registry record for interpreting the trial is the absence of numerical primary outcome results and reported analyses. Although the motor endpoint, its scale, and its assessment times are described, the record does not provide means, standard deviations, treatment contrasts, confidence intervals, or p-values. The direction, magnitude, and precision of any active-versus-sham difference are therefore not available.

The primary outcome was collected at multiple time points, and the record explicitly notes that it was not reduced to one comparison. No analysis plan explains how these measurements were intended to be combined or compared. The record also does not state how treatment sequence, period, or within-participant dependence was handled.

The motor-analysis population excludes one participant because extreme baseline symptom fluctuations confounded measurement of LIFUP-related changes. The record does not report the participant’s data, the impact of the exclusion, or whether other motor outcome data were missing. It does not describe an approach to missing data.

Additional limitations in the available record include the lack of detail about who was masked, how masking was maintained, and how the sham procedure was conducted. Safety information includes counts for serious and other adverse events, but does not include event terms or further follow-up details in the registry record. These are limitations of what the registry record reports; they do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: LIFUP for Treatment of Motor Deficits in Parkinson's Disease — NCT04593875.
• Registry record last updated 2026-02-04; status last verified 2024-08.
• Results first posted 2026-02-04.
• 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

NCT04593875 is a completed randomized, triple-masked crossover study of active and sham LIFUP for motor deficits in Parkinson’s disease. The listed enrollment is 31. Participants were assigned to active-then-sham or sham-then-active sequences, with the second session 2 weeks after the first. The primary outcome was UPDRS Section 3, scheduled before and after LIFUP at Day 1 and Day 15.

The record describes the assessment but does not report numerical primary outcome results or analyses. It notes that one participant was excluded from motor symptom analyses because of extreme baseline fluctuations. Serious adverse event counts were 0 in each session group; other adverse events were reported separately. The record does not report a statistical analysis plan or a primary active-versus-sham effect estimate.