Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes (NCT00845130), a non-randomized na study. The primary outcome is Concentration of Vitamin C in Type 2 Diabetic Patients..

2. Clinical Question

The scientific motivation in the record is that oxidative stress may be relevant to diabetes and that glutathione and vitamin C are antioxidants of interest. The study proposes magnetic resonance imaging techniques to examine brain biomarkers. That rationale explains why cerebral vitamin C was measured; it does not establish that the study demonstrated a difference between groups or that a measured difference would be caused by diabetes.

The main interpretive question is therefore narrower than whether vitamin C infusion changes a biomarker. The stated primary time point is pre-infusion, and no pre/post outcome or treatment-effect estimate is listed. The registry record also does not report the actual concentration summaries, uncertainty estimates, or a statistical test for the group comparison. The posted record supports describing the question and measurement plan, but not a conclusion about the size, precision, or statistical significance of any group difference.

3. Trial Design

The registry describes a completed study with enrollment of 42 and a start date of 2009-09 and primary completion date of 2014-12. Its allocation is listed as non-randomized, masking as none, and model as single group. At the same time, the record identifies diabetic type II subjects and healthy subjects as separate groups. These labels and group descriptions do not establish a randomized two-arm trial; the record itself cautions that the groups are not a like-for-like control comparison.

Both group descriptions state that participants received ascorbic acid (vitamin C) infusion at 1 g/kg, maximum 100gm. The primary outcome timeframe is pre-vitamin C infusion. The outcome description says cerebral concentrations were measured in people with type 2 diabetes and healthy controls. Thus, the primary measurement is described as a comparison of groups before infusion, rather than a comparison of randomized treatment assignments. The registry record does not report a post-infusion concentration endpoint in the primary outcome description.

The primary outcome is a continuous measure, expressed as umol/g tissue, and the listed summary parameter is the mean with standard deviation. The population note says data from one healthy subject were not usable because of movement during MRI scanning. The adverse-event record lists 16 diabetic subjects and 19 healthy subjects at risk for both serious and other events; those figures are not a full account of outcome-specific analysis populations.

Although enrollment is recorded as 42, the record does not explain how enrollment relates to the group-specific at-risk counts or to the usable primary-outcome data. It does not report the recruitment process, eligibility details, allocation mechanism, MRI acquisition schedule, or a protocol for handling all unusable or missing measurements. Phase is listed as NA. The registry record lists no analyses. These omissions limit reconstruction of the conduct and analysis, and they should not be filled in by assumptions about how a biomarker study is usually run.

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 subjects were consented to participate in the study. After baseline information was gathered from labs, it was determined that seven subjects did not meet the inclusion criteria. They were excluded from completing the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Determine cerebral concentrations of vitamin C. Data from one healthy subject were not usable due to subject's movement during MRI scan.

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 Concentration of Vitamin C in Type 2 Diabetic Patients., measured over Pre-Vitamin C infusion.

The primary endpoint is the concentration of vitamin C in brain tissue in type 2 diabetic patients, expressed in umol/g tissue. The stated timeframe is before vitamin C infusion, and the record describes measurements in diabetic patients and healthy controls. It specifies a mean and standard deviation as the summary approach. The record does not include the group means, standard deviations, a difference estimate, confidence interval, or test result.

A cerebral concentration measure is relevant to the study’s stated interest in oxidative stress biomarkers in the brain. The record’s rationale discusses vitamin C as an antioxidant and describes the brain as susceptible to oxidative stress. As a general statistical point, a biomarker provides a measurable feature related to a biological process; measuring it does not by itself prove that the process caused a clinical condition or that changing the biomarker improves health.

Because the measurement is specified before infusion, it does not itself estimate the effect of infusion. A pre-infusion comparison between groups can describe observed group values, but in a non-randomized study it cannot isolate diabetes as the cause of any difference. Interpretation would also depend on the measurement method, available data, and uncertainty around the estimates. Those numerical results and methodological details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the outcome and the comparison the design can support. The primary outcome is a continuous concentration measured in umol/g tissue. The record identifies the mean and standard deviation as the summary statistics. A mean describes the arithmetic center of observed values, while a standard deviation describes their spread around that center. These summaries would help characterize each group, but they are not present in the registry record. Without them, neither the typical recorded concentration nor the variability can be described.

What would a confidence interval express?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical procedure. For a group difference, an interval would convey both the estimated direction and the precision of that estimate. A narrow interval generally indicates greater precision than a wide interval, but precision alone does not establish clinical importance or causality. No confidence interval for the primary outcome is reported in the registry record, so the precision of a possible contrast cannot be evaluated.

What does the design allow?

Random assignment can, in general, make treatment groups comparable in expectation with respect to measured and unmeasured baseline characteristics. That feature is not present: allocation is listed as non-randomized. The record identifies diabetic and healthy groups, but does not describe a random allocation process. A difference in their pre-infusion biomarker measurements could reflect diabetes, other group differences, measurement conditions, or combinations of these factors. A statistical adjustment could sometimes address measured differences, but no adjustment method or covariate set is reported.

The registry also lists a single-group model while describing two participant groups. That metadata does not justify treating the study as a conventional randomized comparison. The clearest design details are that the groups are described separately, allocation is non-randomized, and the record cautions against treating them as like-for-like controls. The record does not explain the apparent tension between the model label and group descriptions.

Why does measurement timing matter?

The outcome timeframe is pre-vitamin C infusion. In general, a measurement made before an intervention can characterize a baseline state, but it cannot estimate change caused by that intervention. Estimating change would require a relevant later measurement and a defined comparison, such as within-person change or a between-group difference in change. The primary outcome description does not specify such an analysis, and the registry record does not report post-infusion results. The infusion listed for both groups therefore should not be confused with evidence about infusion effects.

How should missing measurements be considered?

The record specifically notes that one healthy subject's data were unusable because of movement during MRI scanning. This identifies at least one measurement problem, but does not explain whether there were other missing or unusable observations, how many participants contributed to each endpoint summary, or whether the unusable scan was excluded from every analysis. In general, missingness can affect estimates if the availability of a measurement is related to the value being measured or to group characteristics. Statistical handling depends on the amount and pattern of missing data and on the assumptions behind the method. Those details are not reported.

What is over-dispersion, and is it relevant?

As a general concept, over-dispersion means that observed variation is greater than a statistical model expects. It matters when the model assumes less variability than the data contain, because uncertainty may then be understated. The primary outcome is continuous and summarized by a mean and standard deviation; the registry record does not report a fitted model or indicate that over-dispersion was assessed. It would be inappropriate to claim that it occurred or to infer that a particular correction was used.

What can planning calculations say?

General sample-size planning calculations estimate the number of participants needed for a chosen design, target effect, significance level, and power under stated assumptions. They are not a substitute for observed results. The record describes an illustration based on a fraction of the observed effect, equal allocation between groups, a two-sided significance level of 0.05, and a normal approximation. It also distinguishes participant counts per arm for continuous and other outcomes from event totals for time-to-event outcomes. These assumptions describe a planning framework, not necessarily the original study plan. The record does not report the original sample-size justification, and numerical planning outputs or an observed effect are not included in the registry record for interpretation.

For these reasons, sample-size illustrations should be read as hypothetical planning scenarios rather than observed power. Observed power is not a replacement for an effect estimate and its uncertainty. Where a sponsor-reported analysis and a recalculated result disagree, the sponsor's own analysis takes precedence; however, this record lists no analyses and gives no numerical result to recalculate. No recalculated estimate should be inferred.

What is known about multiplicity and analysis choice?

Multiplicity arises when several hypotheses or outcomes are examined, increasing the chance that at least one result appears statistically notable by chance if each is tested separately. The record lists two outcome measures but lists no analyses. It does not report a multiplicity adjustment, a hierarchy of endpoints, or a prespecified analysis plan. That absence does not prove that no such decisions were made outside the registry; it means they cannot be evaluated from this record. The same limitation applies to model selection, assumptions checks, and the handling of potential confounders.

Overall, the registry offers enough information to identify a continuous biomarker, its units, its pre-infusion timing, and the non-randomized group structure. It does not provide the estimates or analysis details required to judge statistical significance, quantify uncertainty, or reproduce an inferential analysis.

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("Diabetic Type II Subjects", "Healthy Subjects")
n   <- c(16, 18)
m   <- c(1.1, 1.2)
sp  <- c(0.2, 0.1)
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  Diabetic Type II Subjects  16  1.100  0.200  0.993  1.207
CARM  Healthy Subjects  18  1.200  0.100  1.150  1.250

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies two outcome measures and lists no analyses. It does not report how many hypotheses were tested, whether the primary outcome was formally prioritized over other outcomes, or whether any adjustment for multiple testing was planned or performed. In general, when several outcomes or comparisons are examined, multiplicity can increase the chance of at least one apparently notable finding. A prespecified testing hierarchy or adjustment can address that issue, but neither is described in the record. The number of outcome measures alone does not establish that a particular multiplicity problem occurred.

Information about the analysis populations is also limited. Enrollment is 42, and the adverse-event record lists 16 diabetic subjects and 19 healthy subjects at risk. The outcome description notes that data from one healthy subject were unusable because of movement during MRI. The record does not state the exact number of usable measurements in each group, whether any additional measurements were missing, or which participants were included in a primary analysis. Safety denominators should not automatically be treated as endpoint analysis counts.

The registry does not describe a missing-data method, imputation, exclusion rules, or sensitivity analysis. In general, the consequences of missing data depend on how much is missing, why it is missing, and whether missingness is related to the outcome or group. Movement during an MRI scan is a specific reason recorded for one unusable dataset, but it does not establish the pattern or impact of missingness across the study. The record also does not report an analysis plan, covariate adjustment, or treatment of departures from statistical assumptions. These omissions prevent assessment of whether the reported analysis, if any, addressed multiplicity and missing data.

12. 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 0% reporting threshold.

The registry lists no serious adverse events and no other adverse events in the group records. The at-risk counts are 16 for diabetic type II subjects and 19 for healthy subjects, for both the serious-event and other-event entries. These are group-specific safety figures; they should not be read as the number of participants contributing usable primary MRI measurements. The record does not report deaths as a numerical count.

Zero recorded events means that no events are listed in these registry entries. It does not establish that no symptoms or events occurred outside the definitions, observation period, or reporting procedures used for the registry. The record does not provide event definitions, collection methods, follow-up duration for safety, or details of the reporting process. It also does not list serious-event terms.

In general, safety counts are interpreted in relation to the number of people at risk and the completeness of follow-up and reporting. The registry figures alone do not support a comparison of safety between groups, particularly because allocation was non-randomized and the record does not explain whether safety ascertainment was identical. These entries describe what was recorded, not a comprehensive determination of risk.

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

The record describes a study of cerebral vitamin C concentrations in type 2 diabetic patients and healthy subjects, with the primary measurement specified before vitamin C infusion. It provides a biological rationale related to oxidative stress and identifies MRI-based measurement as the approach of interest. These details establish the research question and context, but not the outcome finding.

The primary concentration summaries and any comparison estimate are not reported in the registry record. Therefore, the posted record does not show whether concentrations differed between the groups, how large any difference was, or how precise an estimate might be. It also does not report a statistical test or confidence interval. A missing result must not be interpreted as evidence of no difference, just as the study rationale must not be mistaken for evidence that a difference was found.

Even if a group contrast were available, the non-randomized design would limit causal interpretation. The record explicitly cautions that the diabetic and healthy groups are not a like-for-like control comparison. Differences could be associated with diabetes, but other characteristics of the groups could also contribute. The record does not report adjustments that would address such differences.

The primary timeframe is pre-infusion. As a result, this endpoint cannot by itself establish whether vitamin C infusion changed cerebral vitamin C concentration. The record describes infusion in both groups, but it does not provide a post-infusion result or change estimate in the primary outcome description. Nor does the biomarker endpoint establish a clinical effect on diabetes or its complications. The statistical meaning is limited to the intended measurement and group comparison; the numerical evidence needed to characterize that comparison is absent.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why the question, design, and available results must be distinguished. The registry gives a biological rationale for measuring cerebral vitamin C, identifies a continuous endpoint and its units, and describes diabetic and healthy groups. Yet the non-randomized allocation means those groups should not automatically be interpreted as exchangeable controls. The record itself flags this limitation.

Timing is another essential design feature. Although vitamin C infusion is described for both groups, the primary endpoint is explicitly measured before infusion. Recognizing that distinction prevents a baseline biomarker comparison from being misread as an intervention effect. A study can include an intervention and still have a primary outcome that addresses a different question.

The record also illustrates the importance of reporting estimates, not just a research aim. Without group summaries, a contrast, or an uncertainty measure, readers cannot judge the observed size or precision of the primary outcome. The absence of an analysis listing further limits assessment of how the data were handled. The note about an unusable MRI dataset shows why outcome-specific denominators and missing-data explanations matter, while leaving the broader analysis population unclear.

Finally, planning calculations and observed findings answer different questions. A planning illustration based on an observed effect does not replace reporting the effect, its uncertainty, and the analysis that generated it. The record's design assumptions can help frame how such calculations work in general, but no numerical outcome or planning result is reported. These distinctions are central to transparent interpretation of clinical biomarker research.

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.

Several trial-specific limitations affect interpretation. The study is non-randomized, has no masking, and compares diabetic type II subjects with healthy subjects. The registry record cautions that these groups are not a like-for-like control comparison. Consequently, any group difference would not by itself identify diabetes as its cause. The record does not describe participant characteristics or an adjustment strategy that might help account for group differences.

The registry metadata labels the model as single group while separately describing diabetic and healthy groups. It does not explain this apparent mismatch. The record also describes vitamin C infusion in both groups, while the primary endpoint timeframe is before infusion. No numerical post-infusion result or response analysis is reported, limiting what can be said about the intervention.

The primary outcome has no posted numerical summaries, comparison estimate, confidence interval, or p-value. There is no listed analysis, and the record does not state the original sample-size justification, statistical plan, or missing-data approach. The stated enrollment does not resolve the endpoint-specific analysis counts. One healthy subject's MRI data were unusable because of movement, but the extent of any additional missingness is not reported.

Other relevant details are also absent, including eligibility criteria, recruitment methods, measurement procedures, and the timing and completeness of safety follow-up. The absence of these details from the registry record does not establish that they were not addressed in study conduct; it limits what can be evaluated from the record. Taken together, these limitations prevent a quantitative assessment of the primary result and constrain causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes — NCT00845130.
• Registry record last updated 2018-05-03; status last verified 2018-04.
• Results first posted 2016-07-21.
• 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

NCT00845130 is a completed, non-randomized study titled “Quantitative in Vivo Biomarkers of Oxidative Stress in Diabetes.” Enrollment is recorded as 42, with a start date of 2009-09 and primary completion date of 2014-12. The record describes diabetic type II subjects and healthy subjects, with vitamin C infusion listed for both groups.

The primary outcome is cerebral vitamin C concentration in umol/g tissue before infusion, summarized as a mean and standard deviation. One healthy subject's MRI data were unusable because of movement. The registry lists 16 diabetic subjects and 19 healthy subjects at risk in the adverse-event entries, with zero serious and zero other events recorded in those groups.

The registry record lists no analyses and does not report numerical primary outcome results, a statistical comparison, or a confidence interval. Its non-randomized design and explicit caution about the groups limit causal interpretation of any potential group contrast.