Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN) (NCT00726713), a randomized phase 4 study. The primary outcome is Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks.

2. Clinical Question

3. Trial Design

This was a phase 4, randomized, quadruple-masked, parallel-group, placebo-controlled study. The official title describes a multisite study lasting 24 weeks. The registry record reports enrollment of 214 and a completed status. It lists Pamlab, Inc. as the sponsor. The study began in 2008-06, and primary completion was recorded in 2010-05.

Participants were assigned to Metanx or Metanx placebo. The registry summary describes the treatment period as 6 months, while the official title and primary endpoint timeframe describe 24 weeks. The active intervention is identified as a medical food containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin. Both interventions are classified as other in the registry record, rather than as a drug category.

Randomization and masking are design features intended to reduce bias. Random assignment can balance measured and unmeasured characteristics on average, although it does not guarantee identical groups. Masking can limit the influence of treatment expectations on participants, clinical staff, outcome assessment, or analysis; the registry record labels masking as quadruple but does not specify the roles masked or the procedures used to maintain masking.

The primary endpoint was change from baseline in VPT at 24 weeks. The record also lists secondary outcomes covering symptoms, disability, laboratory markers, quality of life, pain rating, mood measures, and inflammatory markers. The statistical analysis plan, allocation procedure, eligibility criteria, and analysis populations are not reported in the registry record. The stated enrollment should therefore be read as a trial-level figure, not as evidence about the number analyzed for a particular endpoint.

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: Inclusion criteria included individuals 25 and 80 years of age, documented diabetes Type 2, Peripheral polyneuropathy, adequate lower extremity vascular status, and subject competence. 17 exclusion criteria including an HbA1c \>9, uncontrolled heart or lung disease, and vitamin B supplementation, contributed to the number of screening failures.

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 From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks, measured over VPT was measured a 0 (baseline), and 24 weeks.

The primary endpoint was change from baseline in vibration perception threshold at 24 weeks. VPT is a continuous measurement recorded in volts. The registry description specifies a range of 25-45 volts at the hallux, or great toe, on either leg. A VPT meter was used on the great toe of each foot, and the primary measure was the mean VPT across both toes.

In general, a sensory threshold measure represents the stimulus level at which a person perceives vibration. Measuring both feet and averaging the two readings creates a single continuous summary for the endpoint, as described in this record. A change-from-baseline endpoint compares the follow-up measure with the participant's baseline measure. A between-group analysis of change can describe whether the average change differed between the assigned groups, but the registry record does not provide the numerical group changes or a between-group estimate.

The record identifies the endpoint's unit, measurement locations, summary method, and assessment times. It does not report details such as instrument calibration, assessor training, repeat-measurement procedures, or a clinically meaningful threshold for interpreting a difference. Those details are not reported in the registry record. Without a posted estimate and its uncertainty, the direction, magnitude, and precision of the primary endpoint result cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a continuous primary measure summarized as a mean, with standard deviation as the stated dispersion measure. It does not report the primary group means, standard deviations, change estimates, or inferential comparison. The statistical concepts below are general explanations of how such results are commonly read, not a description of an unreported analysis plan.

What does a mean summarize?

In general, the mean is an average that gives each measured value equal weight. For a continuous endpoint such as VPT, a mean can describe the central level in a group or the average change from baseline. The mean alone does not show how similar or different individual measurements were. A mean change also does not by itself identify the treatment contrast: interpretation ordinarily requires comparing the change in one assigned group with the change in the other.

The registry description says that VPT was measured at the great toe of each foot and averaged across both toes. That endpoint construction should be distinguished from the across-participant group mean. Averaging the two toe readings creates a participant-level summary as described in the record; a group summary then describes measurements across participants. The record does not state how missing readings from one foot, if any, were handled.

Why report a standard deviation?

In general, a standard deviation describes the spread of individual observations around a mean. A larger standard deviation indicates more variability among measured values, while a smaller one indicates that observations tend to be closer to the mean. It is not the same as the standard error, which describes uncertainty in an estimated mean, and it is not a confidence interval. Since the registry record does not report the VPT means or standard deviations, neither the average change nor the variability of the primary outcome can be evaluated.

What would a between-group estimate mean?

In general, a between-group estimate expresses the contrast between outcomes under the two assigned conditions. For a change-from-baseline outcome, that contrast may compare average changes, or it may come from a model that adjusts for baseline measurement. These approaches are not automatically interchangeable. The registry record does not report which approach was used, whether baseline adjustment was applied, or the model specification. It is therefore not appropriate to attribute a particular method to this trial.

A confidence interval, in general, communicates statistical uncertainty around an estimate under the model and assumptions used. Its width reflects both the amount of information and the variability in the data. A narrow interval indicates greater precision than a wide interval, but precision is not the same as importance. The registry record does not report a confidence interval for the primary endpoint.

What does a p-value contribute?

In general, a p-value measures how unusual the observed data, or more extreme data, would be under a specified null hypothesis and analysis model. It does not measure the size of an effect, the probability that the null hypothesis is true, or the probability that a result will replicate. Interpretation depends on the endpoint, the analysis, and the broader set of comparisons. No primary endpoint p-value or statistical test is reported in the registry record.

Why can dispersion affect an analysis?

General statistical models often rely on assumptions about how observations vary. If the observed variability is greater than a model anticipates, standard errors and uncertainty estimates can be too small unless the analysis accounts for that extra variation. This issue is often called over-dispersion in settings where a model expects less variability than the data show. It is a general consideration, not a reported feature of this VPT analysis; the registry record does not provide the data or model diagnostics needed to assess it.

How should planning illustrations be understood?

In general, sample-size planning calculations describe the number of participants that would be needed under chosen assumptions about an effect, variability, significance level, allocation, and statistical model. They are planning illustrations, not observed trial outcomes and not observed power. The record describes an illustration based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also distinguishes the convention for time-to-event calculations from the convention for other outcomes. These stated assumptions do not establish that they were used to design this trial. The registry record does not report the trial's own sample-size justification or statistical plan, and no planning calculation should be mistaken for a result observed in participants.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures and 11 analyses, including the primary VPT outcome and multiple secondary outcomes. The secondary measures span symptoms, disability, laboratory markers, health status, pain rating, inflammatory markers, and mood. Examining several outcomes or comparisons can create a multiplicity issue: in general, the more hypotheses assessed, the more opportunities there are for a nominally unusual result to occur by chance if each is interpreted separately.

Multiplicity methods may adjust significance thresholds, control a family-wise error rate, or use other strategies suited to the analysis. They can also define which outcomes are confirmatory and which are exploratory. The registry record does not report whether any adjustment was made, what family of comparisons would have been considered, or whether outcomes were ranked or otherwise prioritized beyond the labels in the record. The IL-6, TNF-α, and HADS outcomes are explicitly identified as exploratory in the listed descriptions; that label alone does not provide a complete multiplicity plan.

Missing-data handling can also affect interpretation. In general, results may depend on whether all randomized participants are included, whether participants with incomplete measurements are excluded, and whether a model or imputation procedure is used to address missing observations. The registry record does not report missingness by outcome, reasons for missing measurements, imputation, sensitivity analyses, or the analysis population for the primary endpoint. The number enrolled should not be assumed to be the number analyzed.

Likewise, the registry record does not report a prespecified statistical analysis plan, interim analyses, or sample-size justification. These omissions do not show that such procedures were absent; their details are not reported in the registry record. They limit the ability to assess how outcome selection, incomplete data, and multiple comparisons were addressed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transient ischemic attack (1.9%), death (1.9%), knee arthroplasty (0.9%), ligament operation (0.9%), cardiac failure, congestive (0.9%).

The safety entries report serious adverse events for 5 of 106 participants at risk in the Metanx group and 8 of 108 at risk in the placebo group. For other adverse events, the registry lists 25 of 106 at risk in the Metanx group and 27 of 108 at risk in the placebo group. These are separate registry counts; they should not be combined, and the record does not provide enough detail to determine overlap between serious and other adverse-event categories.

The listed serious-event terms and percentages are Transient Ischemic Attack, 1.9%; Death, 1.9%; Knee arthroplasty, 0.9%; Ligament Operation, 0.9%; Cardiac Failure, Congestive, 0.9%; and Breast Cancer, 0.9%. The listing does not assign these terms to a treatment group in the information reported, so group attribution should not be inferred from the percentages. Although Death appears among the listed serious-event terms, the group-level deaths field is not reported in the registry record.

In general, adverse-event counts describe events recorded during a study; they do not by themselves establish that the intervention caused an event. The registry entries do not provide event-level timing, duration, relatedness assessments, or detailed definitions for these counts. They should be read as a limited safety description, not as a complete comparison of safety profiles.

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

The record describes a randomized, quadruple-masked, placebo-controlled comparison of Metanx with placebo in people with type 2 diabetic peripheral neuropathy. It specifies the primary endpoint as change from baseline in VPT at 24 weeks and explains how the toe measurements were summarized. These design details clarify what the trial set out to assess.

However, the primary outcome estimate is not reported in the registry record. There is no numerical group change, between-group contrast, confidence interval, or p-value available in the record for the primary endpoint. Without those results, it is not possible to state the direction or magnitude of the observed difference, assess its precision, or judge whether the data are compatible with a range of possible effects.

The same caution applies to the listed secondary outcomes. Their presence shows that the study planned or recorded several additional measurement domains, but the outcome names alone do not reveal their findings. The safety entries report counts and serious-event terms, but they do not supply detailed event-level context or a complete basis for attributing events to the intervention.

In general, a statistically detectable difference and a clinically meaningful difference are distinct questions. Statistical uncertainty concerns how precisely an effect is estimated; clinical importance depends on the meaning of the measure and the size of a difference that matters in context. The registry record does not state a clinically meaningful VPT threshold or report an estimate that would permit those questions to be assessed.

The appropriate interpretation is therefore bounded: the registry record documents a trial design, outcome definitions, selected safety counts, and a broad set of outcomes, but it does not report the primary numerical result. It cannot support a conclusion about whether Metanx changed VPT relative to placebo, nor about the size, precision, or clinical importance of such a change.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly described research question and a result that can be quantitatively interpreted. The registry record identifies a randomized parallel-group comparison, masking, a placebo comparator, and a continuous primary endpoint. Those features help readers understand the intended contrast and the measurement used to address it.

At the same time, design labels do not replace outcome estimates. Randomization can strengthen a between-group comparison by reducing confounding on average, while masking can reduce some forms of measurement or expectation-related bias. Neither feature establishes the direction or size of an outcome difference. For that, readers need the group results, the analysis contrast, and uncertainty information; these are not reported for the primary endpoint in the registry record.

The broad outcome list also illustrates why multiplicity and analysis transparency matter. The record includes 11 outcome measures and 11 analyses, and it labels some outcomes as exploratory. In general, an analysis plan helps readers distinguish confirmatory questions from exploratory ones and understand how multiple comparisons are handled. The registry record does not report these details.

Finally, the safety entries show why counts need context. Group-specific counts at risk and adverse-event counts are useful descriptive information, but event definitions, timing, relatedness, and analysis rules influence interpretation. The record reports only part of that context. Statistically, the key lesson is that a trial's design and registered endpoints describe what was intended to be studied; they are not substitutes for estimates that show what the observed data support.

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 primary limitation for interpreting efficacy is that the registry record does not report a numerical result for the primary VPT comparison. It also does not provide group-specific outcome summaries, an effect estimate, confidence interval, or p-value. Although the endpoint definition identifies the measurement sites, unit, summary method, and assessment times, it does not report the measurement protocol in enough detail to evaluate instrument procedures or assessor consistency.

The record does not describe the statistical model, baseline adjustment, handling of repeated measurements, or analysis population. It does not report participant flow, outcome-specific denominators, missing-data patterns, or sensitivity analyses. The listed enrollment figure cannot establish how many participants contributed data to the primary analysis.

Several outcome measures and analyses are listed, but the registry record does not describe a multiplicity strategy or a full hierarchy of confirmatory and exploratory questions. It labels some secondary outcomes as exploratory, yet does not report the broader analysis plan. The sample-size assumptions described in the record are planning-illustration assumptions, not the trial's own sample-size justification.

For safety, counts and selected serious-event terms are reported, but the record does not provide event-level detail, group attribution for the listed terms, timing, relatedness, or a reported group-level death count. These limitations restrict interpretation of both outcome and safety information. They do not establish that unreported procedures or data were absent; those details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN) — NCT00726713.
• Registry record last updated 2013-08-30; status last verified 2013-07.
• Results first posted 2013-08-30.
• 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

NCT00726713 is a completed phase 4 randomized, quadruple-masked, parallel-group study of Metanx versus placebo in people with type 2 diabetic peripheral neuropathy. The registry record reports enrollment of 214 and describes a 24-week, multisite study sponsored by Pamlab, Inc. The primary endpoint was change from baseline in VPT at 24 weeks, measured in volts and averaged across the great toes.

The record lists 11 outcome measures and 11 analyses, as well as group-level serious and other adverse-event counts. It does not report a numerical primary endpoint comparison, its uncertainty, the statistical analysis plan, or the handling of missing data and multiplicity. Therefore, the design and endpoint can be described, but the primary result's direction, magnitude, and precision cannot be assessed from the registry record.