tDCS and Glucose Uptake in Leg Muscles: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for tDCS and Glucose Uptake in Leg Muscles (NCT04016844), a na na study. The primary outcome is Glucose Uptake in Leg Muscles.

2. Clinical Question

The study description focuses on glucose uptake in the more- and less-affected legs during walking in people with multiple sclerosis. Participants were assessed in a single group, with tDCS and sham conditions described across the imaging sessions. This is therefore a within-participant condition comparison in the study description, not a comparison between independently assigned treatment and control groups. The registry record does not explain how the order of conditions was determined.

The clinical motivation in the brief summary is to examine tDCS in relation to walking. The primary endpoint, however, is a PET-derived measure of glucose-uptake asymmetry, not a direct measure of walking performance. Ratings of Perceived Exertion are listed as a secondary outcome. The record does not report outcome results for either measure, so the clinical question cannot be answered from the posted results described in the registry record.

3. Trial Design

The registry record describes a completed, single-group study of tDCS and sham stimulation in people with multiple sclerosis. It lists an enrollment of 4, an allocation of NA, and no phase classification. The study dates are recorded as starting on 2019-12-06, with primary completion on 2020-10-01. The record does not provide a randomized, parallel-group treatment comparison.

The brief summary describes three laboratory sessions. In the first, participants were to complete the Patient Determined Disease Steps, the Fatigue Severity Scale, and maximal voluntary contractions of the right and left knee extensors and flexors. These assessments were intended to identify the more-affected leg. The next two sessions involved whole-body FDG PET imaging. Participants walked on a treadmill at a self-selected speed for 20 min while receiving either tDCS or sham stimulation, followed by PET/CT imaging. The description says the other condition was used in the third session.

The record does not report the method used to assign or determine condition order, whether washout was used, or whether participants or assessors were blinded in practice. Its masking classification is NONE, while the brief summary describes tDCS or sham being applied in a blinded manner. The registry record does not reconcile these descriptions. Further details about conduct, deviations, and the analysis population are not reported in the registry record.

The record lists Glucose Uptake in Leg Muscles as the primary outcome, with a timeframe of Six Months, and Ratings of Perceived Exertion as a secondary outcome. Although the study status is COMPLETED, the registry record does not report numerical outcome results or analyses for these outcomes.

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: All 4 Subjects completed active tDCS first and then SHAM.

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.

Population: 4 participants completed tDCS and SHAM.

6. Primary Endpoint

The registry lists the primary outcome as Glucose Uptake in Leg Muscles, measured over Six Months.

The primary endpoint is leg-muscle glucose-uptake asymmetry measured with PET after treadmill walking under tDCS or sham. The record says FDG was administered by intravenous injection during the walking session and that a whole-body PET/CT scan was then acquired. SUV asymmetry indices compare uptake in the less-affected leg with uptake in the more-affected leg, scaled by their average. The record defines an index of at least 10% as asymmetric.

This measure is intended to describe how unevenly glucose uptake is distributed between the two legs. Comparing the index across the tDCS and sham conditions could describe whether the measured asymmetry differs between those conditions in the study group. It is not itself a direct measure of walking ability, and the record does not establish that a change in this PET measure corresponds to a change in walking.

The endpoint is reported as a mean with standard deviation, in percentage units. The timeframe is listed as Six Months, but the registry record does not clarify how that timeframe relates to the described imaging sessions. It also does not report the observed means, standard deviations, participant-level values, or a condition contrast. Therefore, the direction and precision of any observed difference are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as a continuous outcome summarized by a mean and standard deviation. In general, a mean describes the center of a set of measurements, while a standard deviation describes how spread out those measurements are around the mean. These summaries help describe an outcome, but they do not by themselves show the uncertainty in a comparison between conditions. The outcome summaries and any comparison estimates are not reported in the registry record.

What would a condition contrast represent?

Because the study description uses both tDCS and sham in the same single group, the relevant comparison would ordinarily be based on each participant's measurements under both conditions. A within-participant contrast asks how the endpoint differs between conditions for the same person, then summarizes those differences across the group. This differs from comparing the average outcome in one group with the average outcome in a separate group. The registry record does not report a condition contrast, its standard error, or the method used to estimate it.

In general, a confidence interval expresses the range of values compatible with an estimate under a specified statistical model and procedure. A narrower interval indicates greater precision, while a wider interval indicates less precision. A confidence interval would help readers judge whether the estimated condition difference is precise enough to distinguish among meaningfully different possibilities. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed.

How should a significance test be read?

In general, a p-value describes how incompatible the observed data are with a specified null model, assuming the model and its assumptions hold. It does not measure the size or clinical importance of an effect, and it does not give the probability that the null hypothesis is true. A p-value is most informative when read alongside an estimated effect and its uncertainty. The registry record lists no analysis results or p-values for the primary endpoint, so significance testing cannot be interpreted for this study.

The study's repeated-condition structure matters for the choice of analysis. A method for independent groups would not reflect the pairing of two condition measurements from the same participant. In general, paired analyses use the within-participant differences and their variability. A repeated-measures model may also be considered when there are multiple observations or additional structure, but the registry record does not report which method, if any, was used. It would be inappropriate to infer an analysis plan from the endpoint description alone.

What do the planning illustrations mean?

In general, a sample-size calculation estimates how many participants a future study might need under specified assumptions about the effect, variability, significance level, allocation, and statistical method. The registry record describes the accompanying calculations as planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These assumptions are not evidence that the study itself used those design choices.

Such calculations are not observed power. Observed power is not a substitute for reporting an estimated effect and its uncertainty; after a study is conducted, those estimates are more informative about what the data show. The record does not report the observed effect or the numerical planning outputs in the registry record used for this explanation. The illustrated two-arm allocation also differs from the registry's description of one group undergoing both conditions. Accordingly, these planning calculations should not be interpreted as a retrospective assessment of the completed study's ability to detect a difference.

What assumptions remain unclear?

Statistical interpretation depends on how the paired observations were obtained and handled. The registry record does not report the condition-order procedure, the handling of missing measurements, or whether any adjustments were made for session order. In general, order effects can matter when measurements are repeated because participants' responses or measurement conditions may change across sessions. A model or design strategy may address such effects, but none is specified in the registry record.

Outcome distribution and influential observations can also matter, especially in a small study. General statistical practice would examine whether the chosen summary and model are appropriate to the data and would avoid treating a normal approximation as automatically valid. The registry record does not report distribution checks, diagnostics, transformations, or sensitivity analyses. No method or result should be attributed to the study without a registry report of it.

Finally, the endpoint definition sets an asymmetry threshold of at least 10%, but that definition does not replace analysis of the continuous index. In general, categorizing a continuous outcome can discard information about how far measurements lie above or below a cutoff. The registry record describes the threshold as a way to classify asymmetry; it does not report whether a separate categorical analysis was conducted. The continuous outcome's numerical results and any threshold-based findings are not reported in the registry record.

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("tDCS Effects on Glucose Uptake in Leg Muscles", "SHAM Effects on Glucose Uptake in Leg Muscles")
n   <- c(4, 4)
m   <- c(6.3, 16.4)
sp  <- c(6.2, 13.6)
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  tDCS Effects on Glucose Uptake in Leg Muscles  4  6.300  6.200  -3.566  16.166
CARM  SHAM Effects on Glucose Uptake in Leg Muscles  4  16.400  13.600  -5.241  38.041

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists Glucose Uptake in Leg Muscles as the primary outcome and Ratings of Perceived Exertion as a secondary outcome. It also states that there are two outcome measures, but does not provide a complete account of the analyses performed. The count of outcome measures alone does not establish how many statistical tests were conducted or how hypotheses were prioritized beyond the primary and secondary labels.

Multiplicity arises when several outcomes, time points, regions, or comparisons are tested. In general, conducting many tests can increase the chance of at least one apparently unusual result if all are interpreted without accounting for the number of tests. A statistical plan may specify a primary test, adjustment procedures, or a hierarchy of hypotheses. Such a plan and any multiplicity adjustment are not reported in the registry record. The record also does not describe whether multiple muscle regions or other PET measures were analyzed separately.

Missing-data procedures are not reported in the registry record. It does not state whether any participants lacked one of the condition measurements, whether scans were excluded, or how incomplete outcome data would be handled. No assumption about complete data, imputation, or exclusion should be made.

The registry record does not define an analysis population, such as all enrolled participants or participants with usable measurements under both conditions. It lists an enrollment of 4, but that entry alone does not establish how many participants contributed to the primary endpoint analysis. The number included in an analysis and the reasons for any exclusions are not reported in the registry record. These omissions limit interpretation of both the representativeness of the reported results and the potential for bias from missing or excluded observations.

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 registry record lists one adverse-event group titled “tDCS/SHAM Effects on Glucose Uptake in Leg Muscles.” It records 4 at risk for serious adverse events and 0 affected, and records 4 at risk for other adverse events and 0 affected. Deaths are recorded as 0, and no serious-event terms are listed.

These entries describe the events recorded in the registry, not proof that no adverse events of any kind occurred. The record does not provide event definitions, surveillance procedures, severity details for non-serious events, or an account of the time period over which events were collected. It also does not separate safety findings by tDCS and sham condition. The one-group presentation does not support a between-group safety comparison.

In general, zero recorded events in a small study do not establish that an intervention has no risk. The event counts should be read in the context of the limited enrollment and the registry's lack of further safety detail. They should not be interpreted as a precise estimate of event frequency or as a comparison of the safety of tDCS with sham.

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

The study record describes a completed investigation of tDCS and sham stimulation during treadmill walking, with leg-muscle glucose-uptake asymmetry as the primary outcome. It gives procedural details about the walking sessions, FDG administration, and PET/CT imaging. It also defines how the asymmetry index was calculated and identifies the threshold used to classify asymmetry.

Those details explain what the investigators intended to measure; they do not establish what the study found. The registry record does not report the primary outcome values, an estimated difference between conditions, a confidence interval, or a statistical test. As a result, the size, direction, and precision of any difference are not reported in the registry record. The record also does not report numerical results for the secondary outcome, Ratings of Perceived Exertion.

The endpoint is a PET-based measure of relative glucose uptake between legs. It should not be treated as interchangeable with walking performance, fatigue, or a participant's overall clinical status. The brief summary gives walking as the study's motivation, but no walking-performance result is reported as the primary outcome. The record does not establish whether a difference in glucose-uptake asymmetry would correspond to a meaningful change in walking or other outcomes.

The design description uses both conditions in one group. It does not describe randomized allocation to separate arms, and condition order is not reported. Even if numerical results were available, interpretation would require attention to the paired nature of the observations and to possible order or session effects. No statistical method addressing those issues is reported.

Thus, the registry record supports an account of the research question and measurement approach, but not a conclusion about an observed effect. Completion status, the outcome definition, and the safety entries do not replace outcome estimates. The absence of posted estimates also means that their uncertainty and robustness cannot be judged.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a clear measurement description and a report of statistical findings. The registry record specifies a PET-derived endpoint, its units and summary form, and a formula for comparing uptake between legs. Yet without outcome values or an estimated contrast, readers cannot determine how the endpoint varied across conditions or how precisely any difference was estimated.

The single-group structure is also important. The description involves tDCS and sham conditions in the same group, so an analysis should reflect paired observations rather than assume independent treatment and control groups. The registry record does not report condition order or the analysis method. This makes design details essential for interpreting any future-reported contrast, especially in a study with a limited enrollment.

The record further shows why planning calculations should be separated from observed evidence. Calculations based on an observed effect and hypothetical two-arm assumptions may illustrate planning scenarios, but they are not a substitute for estimates from the completed study and do not indicate observed power. The stated planning setup differs from the described single-group condition comparison, so its assumptions require careful interpretation.

Finally, the endpoint's meaning should be kept distinct from the broader clinical motivation. Glucose-uptake asymmetry is a physiological imaging measure; it is not itself a measure of walking performance. A statistically interpretable account would need to report the outcome data, the within-participant contrast, its uncertainty, the analysis population, and relevant missing-data and order-handling details. Those elements are not reported in the registry record.

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 does not report primary or secondary outcome results, despite listing the study as completed. It therefore offers no outcome estimate, uncertainty interval, or statistical test with which to assess the findings. The record lists an enrollment of 4, but does not report how many participants contributed usable measurements to each condition or outcome.

The study is described as a single group exposed to both tDCS and sham, without randomized allocation. The method for determining the sequence is not reported, nor are details about possible period or carryover effects. The record's masking classification is NONE, while its brief summary describes blinded application of tDCS or sham. The nature and extent of any blinding are not clarified.

The primary outcome timeframe is listed as Six Months, while the procedure describes imaging sessions after treadmill walking. The registry record does not explain the relationship between this timeframe and the imaging measurements. It also does not report the analysis method, handling of missing data, analysis population, or any multiplicity strategy.

The outcome is a PET-derived measure of asymmetry, and the record does not report whether it was linked to a direct measure of walking. Ratings of Perceived Exertion are listed as a secondary outcome, but no results are reported. The adverse-event entries provide counts but little detail about monitoring, event definitions, or condition-specific safety. These limitations leave both the efficacy-related interpretation and the safety context incomplete.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: tDCS and Glucose Uptake in Leg Muscles — NCT04016844.
• Registry record last updated 2023-01-25; status last verified 2023-01.
• Results first posted 2023-01-25.
• 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

NCT04016844 is listed as a completed study sponsored by the University of Iowa. The registry record describes a single group of people with multiple sclerosis receiving tDCS and sham during treadmill walking, with PET/CT imaging to measure leg-muscle glucose uptake. Enrollment is listed as 4. The recorded start date is 2019-12-06 and the primary completion date is 2020-10-01.

The primary outcome is Glucose Uptake in Leg Muscles, summarized as a mean with standard deviation, with a stated timeframe of Six Months. Ratings of Perceived Exertion is listed as a secondary outcome. The record gives an asymmetry-index definition and classifies values of at least 10% as asymmetric. It does not report numerical outcome results or statistical analyses. Serious adverse events, other adverse events, and deaths are each recorded as 0 in the listed group.