Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD (NCT03647137), a registered phase not stated study. The primary outcome is Striatal FEOVB PET Binding.

2. Clinical Question

The registry describes the study as linking detailed motor testing with PET imaging. Its brief summary places the question in the context of differences in dopamine responsiveness and the occurrence of freezing of gait. The record does not report a formal hypothesis specifying the direction or size of an expected association, nor does it state a primary comparison between particular groups. Consequently, the study question is best read as an investigation of relationships among the measured imaging features and gait findings, rather than as a test of a treatment effect.

3. Trial Design

The registry record describes a completed study of Parkinson’s disease with enrollment of 53. The listed intervention is detailed motor testing, including assessment of freezing of gait. The group descriptions also state that participants underwent brain PET imaging. The study is organized around four categories defined by freezing of gait observed during motor assessment in relation to dopaminergic medication status: no observed freezing, freezing only while off medication, freezing worse while off medication, and freezing described as equivalent on and off medication.

The record does not report a randomized allocation. It explicitly notes that the groups are not a like-for-like control comparison. These categories therefore should not be interpreted as randomized treatment arms. The medication status is part of the way the motor-test groups are described; the record does not describe an assigned medication intervention for this study. It also does not give further details about recruitment, eligibility criteria, masking, or the timing and order of motor assessments and imaging. Those details are not reported in the registry record.

The registry lists a start date of 2016-06-07 and a primary completion date of 2021-05-26, with status recorded as completed. The primary outcome timeframe is stated as through study completion, an average of 6 months. The sponsor is the VA Office of Research and Development. The registry also lists serotonergic innervation of the striatum and freezing as a secondary outcome. The record does not provide a complete account of the analysis plan or explain how the different clinical groups were intended to be compared.

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: 2 participants were excluded before assignment because they showed a normal dopaminergic PET brain scan prior to motor assessment. 7 participants were excluded before assignment because they didn't consent to being recorded on camera during motor assessment. Another 7 participants were dropped for showing normal dopaminergic scan after motor assesment, which precluded them from being assigned into groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only participants that have freezing of gait during either on or off meds motor assesment.

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 Striatal FEOVB PET Binding, measured over through study completion, an average of 6 months.

The primary endpoint is titled Striatal FEOVB PET Binding. It is described as the parametric distribution volume ratio of FEOVB, a cholinergic PET tracer, in the striatum. A distribution volume ratio is an imaging measure used to characterize tracer binding in a target region. In general, PET tracer binding can serve as an indirect measure related to the biological system targeted by the tracer; it is not itself a direct measurement of gait or a clinical benefit.

The endpoint is relevant to the stated study question because the registry describes an interest in cholinergic PET imaging and the relation between brain imaging features and freezing of gait. The group descriptions mention 18F-FEOBV imaging, while the primary outcome title and description use FEOVB. The registry record does not explain this naming difference, so the endpoint is referred to by its stated primary-outcome name.

The registry describes the outcome as a mean, with standard deviation as the dispersion measure. That identifies how the outcome is intended to be summarized, but does not reveal the observed mean or variability. Neither the primary endpoint values nor a between-group estimate is reported in the registry record. The endpoint timeframe is through study completion, an average of 6 months; the record does not give further details about the measurement schedule.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is continuous: striatal FEOVB PET binding is expressed as a distribution volume ratio. The registry specifies a mean as the summary measure and standard deviation as the measure of dispersion. In general, a mean provides a summary of the central level of a continuous measurement, while the standard deviation describes the variation of individual measurements around that mean. Both are useful for describing data, but neither alone shows whether group differences are statistically distinguishable or clinically meaningful.

What does a group comparison describe?

For a continuous endpoint, a comparison among clinical groups would ordinarily estimate how the outcome’s distribution or average differs across those groups. In this study the categories are based on observed freezing of gait during motor assessment in relation to medication status. The registry does not report which pairwise or overall comparisons were planned, nor does it give the estimated group means or contrasts. It is therefore not possible to explain a particular contrast or its result.

In general, an estimated difference is most informative when paired with an interval estimate. A confidence interval expresses the uncertainty around an estimate under the assumptions of the statistical method; a narrower interval indicates greater precision, while a wider interval indicates less precision. It does not, by itself, establish that an effect is important or that a causal relationship exists. A confidence interval for the primary outcome is not reported in the registry record. A p-value for that outcome is also not reported. No test, model, or adjustment method is specified, so no particular inferential procedure should be attributed to the study.

Why do the group definitions matter?

These categories are defined by motor findings, not by randomized assignment. The registry explicitly states that the groups are not a like-for-like control comparison. In general, nonrandomized groups can differ in characteristics other than the feature used to define them. A difference in an imaging measure across such groups may be descriptive, but it does not isolate the effect of medication or prove that a PET feature caused freezing of gait. The registry record does not report adjustment variables or a method for addressing potential differences between groups.

The descriptions refer to whether freezing was seen while participants were on or off dopaminergic medication. That language describes the clinical assessment categories; it does not establish how medication was managed for study purposes. The record does not report the medication protocol or the order of the on-medication and off-medication assessments. These design details would be important for interpreting within-person and between-group comparisons, but they are not reported in the registry record.

What do the planning illustrations mean?

The planning illustrations are described as calculations based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The target effect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using those assumptions. The registry record does not report the trial’s own sample-size justification. The illustrations are also not observed power. In general, sample-size calculations describe how many participants per arm would be needed under specified assumptions to detect a target effect with a chosen power; they do not measure the probability that a particular observed result is true.

The reported planning framework uses the observed effect as its reference. Such an illustration depends on the accuracy and stability of that estimate. If the estimated effect is uncertain, a planning value based on it will also be uncertain. The record does not give the numerical observed effect or the numeric planning estimates in the registry record described for this analysis, so no specific sample-size requirement can be interpreted. The planning calculations should not be confused with actual enrollment or the number of participants with analyzable PET data.

Why might variability affect interpretation?

In general, continuous measurements can have different degrees of variability, and greater variability makes it harder to estimate a group average precisely when sample sizes are otherwise unchanged. A standard deviation helps describe that variability. Some continuous outcomes may also show more spread than expected under a simple model. Over-dispersion, in general, means that observed variation exceeds what a statistical model assumes; ignoring it can make uncertainty estimates too optimistic. The registry does not report a distributional assessment or a method addressing over-dispersion for this endpoint. There is no basis in the record to state whether over-dispersion was present or whether it affected the analysis.

Overall, the registry identifies the endpoint summary as a mean with standard deviation, but does not report the analysis method, effect estimate, uncertainty interval, or test result. General statistical concepts can explain how these measures would be read, but they cannot fill in the missing primary-outcome findings.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Parkinson's Disease Without FoG", "Parkinson's Disease With FoG Only While Off-meds", "Parkinson's Disease With FoG Worse While Off-meds", "Parkinson's Disease With FoG Equivalent Between On")
n   <- c(11, 6, 9, 5)
m   <- c(4.89, 5.01, 4.3, 4.06)
sp  <- c(0.7, 0.69, 0.81, 0.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Parkinson's Disease Without FoG  11  4.890  0.700  4.420  5.360
CARM  Parkinson's Disease With FoG Only While Off-meds  6  5.010  0.690  4.286  5.734
CARM  Parkinson's Disease With FoG Worse While Off-meds  9  4.300  0.810  3.677  4.923
CARM  Parkinson's Disease With FoG Equivalent Between On  5  4.060  0.800  3.067  5.053

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and one analysis. It identifies striatal FEOVB PET binding as the primary outcome and lists serotonergic innervation of the striatum and freezing as a secondary outcome. However, the record does not describe how the outcomes were ordered for statistical testing, whether there were multiple group contrasts, or whether any adjustment for multiple comparisons was planned. A multiplicity strategy is not reported in the registry record.

In general, when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed separately without an appropriate plan. Methods for handling multiplicity can control that risk, but the choice depends on the study question and analysis plan. Because no strategy is described, it is not possible to determine how multiplicity was addressed or whether reported inferences were adjusted.

The registry does not report missing-data counts or procedures for handling missing measurements. It also does not specify the analysis population for the primary endpoint, such as which participants were included in the endpoint analysis or how incomplete imaging or motor assessments were treated. Enrollment of 53 should not be interpreted as confirmation that every participant contributed to each outcome analysis.

The record also does not report a statistical analysis plan, interim analyses, or a sample-size justification. These details are important for understanding which analyses were prespecified, how deviations or incomplete observations were managed, and whether the study was planned around a target precision or effect. Their absence does not establish that such procedures were absent in practice; it means they are not reported in the registry record.

12. 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 posted adverse-event figures list four clinical groups. For Parkinson’s disease without freezing of gait, 13 participants are listed as at risk for serious adverse events and 0 as affected; 13 are listed for other adverse events and 0 as affected, with 0 deaths. For freezing only while off medication, the corresponding figures are 7 at risk and 0 affected for serious adverse events, 7 at risk and 0 affected for other adverse events, and 0 deaths. For freezing worse while off medication, the figures are 10 at risk and 0 affected for serious adverse events, 10 at risk and 0 affected for other adverse events, and 0 deaths. For freezing equivalent on and off medication, the figures are 7 at risk and 0 affected for serious adverse events, 7 at risk and 0 affected for other adverse events, and 0 deaths.

These figures describe the registry’s reported adverse-event counts for the stated group denominators. They do not provide details about event definitions, surveillance duration, or how events were collected; those details are not reported in the registry record. The counts should not be treated as evidence that no events could occur outside the reported recording and follow-up. They also do not provide information about the primary imaging outcome or answer the study’s question about freezing of gait and PET measures.

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

The registry record describes a completed study in Parkinson’s disease that connected detailed motor assessment, including freezing of gait, with brain PET imaging. Its primary outcome was striatal FEOVB PET binding, a cholinergic tracer measure expressed as a distribution volume ratio. The record also describes clinical categories based on whether freezing was seen during assessment while on or off dopaminergic medication.

What the registry does not provide is the primary outcome result. The observed mean, standard deviation, estimated group differences, confidence intervals, and p-values are not reported in the registry record. As a result, the direction, magnitude, and precision of any relationship between the PET measure and freezing of gait cannot be evaluated from the record. It is not possible to say from these registry entries whether the groups differed in the primary outcome.

The group categories are not randomized comparisons. Any contrast among them would be an observational description of people classified by motor-assessment findings, not an estimate of the effect of a randomly assigned intervention. The record does not describe methods that would adjust for other group differences. Even if numerical associations were available, an association between imaging and gait status would not by itself establish that one caused the other.

The adverse-event record lists zero affected participants for serious and other adverse events in each group, and zero deaths. These posted counts are limited to the registry’s stated denominators and do not supply the missing primary endpoint findings. They should be read as recorded safety counts rather than as a complete characterization of safety under unspecified surveillance conditions.

Overall, the study record documents a specific imaging and motor-assessment framework, but the numerical primary results and analysis details needed to assess what the investigation found are not reported in the registry record. The completed status alone does not establish the direction or strength of a result.

14. Why This Trial Matters Statistically

This study matters statistically because it illustrates the distinction between a measurement plan and an interpretable result. The registry names a continuous imaging endpoint, identifies its unit as a distribution volume ratio, and states that it is summarized with a mean and standard deviation. Those details clarify what was intended to be measured, but they do not reveal the observed values or the uncertainty around any group comparison.

The group structure also matters. Participants are categorized by observed freezing of gait during motor assessment in relation to dopaminergic medication status. Since the registry explicitly says the arms are not a like-for-like control comparison, the categories should not be read as randomized arms. Statistical descriptions of differences among these groups would not, by themselves, identify a causal effect.

The study also connects a clinical feature with PET measures of brain systems. In general, such work can characterize whether an imaging measure varies alongside a clinical finding. Interpretation depends on clear outcome definitions, suitable analysis methods, and transparent reporting of estimates and their precision. The registry record does not report the numerical primary endpoint results or the analysis methods, so it cannot establish the strength or reliability of such a relationship.

Finally, the record lists multiple outcome measures but does not report a multiplicity approach, missing-data methods, or the primary analysis population. These are not merely technical details: they determine how much confidence readers can place in a set of comparisons and how representative the analyzed observations may be. The record’s limitations are therefore about interpretability, not a basis for inferring an unreported finding.

15. 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 leaves several trial-specific details unresolved. It does not report eligibility criteria, recruitment procedures, or the characteristics of participants beyond the Parkinson’s disease diagnosis and the motor-assessment categories. As a result, the population to which the findings might apply cannot be characterized more fully from this record.

The arm descriptions state that participants underwent imaging with 11C-DBTZ, 18F-FEOBV and 11C-PIB, while the primary outcome title and description refer to FEOVB. The record does not explain the difference in tracer naming. The complete text of some group descriptions is also not available in the record details summarized for this analysis, so further imaging or grouping particulars should not be inferred.

The study is not described as a randomized comparison, and the registry explicitly cautions that the groups are not like-for-like controls. The record does not report whether comparisons were adjusted for potential group differences. The timing and order of motor testing, medication management, and PET imaging are also not reported in the registry record. These features limit interpretation of any potential association.

Most importantly, the numerical primary outcome results, uncertainty estimates, analysis methods, missing-data procedures, and analysis population are not reported. The record also does not report a multiplicity plan, interim analyses, or a trial-specific sample-size justification. The stated primary outcome timeframe is through study completion, an average of 6 months, but further measurement-schedule details are not given. These omissions mean that the planned measurement framework is clearer than the statistical evidence available for judging the study’s findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Amyloidopathy, Cholinopathy, Dopamine Responsiveness and Freezing of Gait in PD — NCT03647137.
• Registry record last updated 2024-01-05; status last verified 2023-03.
• Results first posted 2024-01-05.
• 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.

19. Record Summary

NCT03647137 is a completed study sponsored by the VA Office of Research and Development, with enrollment of 53. The registry lists a start date of 2016-06-07 and a primary completion date of 2021-05-26. The study concerns Parkinson’s disease, detailed motor testing for freezing of gait, and brain PET imaging.

The primary outcome is striatal FEOVB PET binding, described as a cholinergic tracer distribution volume ratio and summarized as a mean with standard deviation. The clinical groups are defined by freezing-of-gait findings in relation to dopaminergic medication status. The registry notes that these are not a like-for-like control comparison.

The record lists serotonergic innervation of the striatum and freezing as a secondary outcome. It does not report the primary numerical results, analysis methods, missing-data handling, or multiplicity approach. Adverse-event counts are reported as zero affected participants and zero deaths in each listed group.