Glutathione and Function in HIV Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Glutathione and Function in HIV Patients (NCT02348775), a na phase 1 study. The primary outcome is Muscle Glutathione Concentration.

2. Clinical Question

The study description proposes investigating whether supplementation is followed by changes in glutathione levels and a range of other measures, including body composition, strength and function, quality of life, mitochondrial energetics, biochemistry, metabolism, cognition and memory. These are stated research aims, not reported findings.

The registry record describes supplementation for 12 weeks and says measurements would continue for a further 2 months after supplementation to examine washout effects. It also describes the supplementation duration as 3 months. The primary outcome is muscle glutathione concentration, measured by liquid chromatography. No numerical result for that outcome is reported in the registry record, so the record does not establish the size or direction of any change.

3. Trial Design

The registry record identifies this as a Phase 1, completed, single-group study with enrollment of 16. It lists Baylor College of Medicine as the sponsor. The recorded study dates are 2014-11 for start and 2018-12 for primary completion. The record describes the study population as people with HIV and focuses its rationale on older patients with HIV.

The intervention is GlyNAC, described as a combination of glycine and n-acetylcysteine, taken orally. The arm description says HIV infected subjects would be studied before and after taking the supplements for 3 months. The brief description also sets out a 12-week supplementation period followed by a further 2 months of measurement for washout. The primary outcome timeframe is listed as 20-weeks.

The design fields state that allocation is not applicable, masking is none, and the model is single group. Accordingly, the record does not describe a randomized comparison. The adverse-event listing nevertheless includes both a GlyNAC Arm and a Control Arm. That administrative listing should not be treated as evidence of a concurrent control comparison: the record explicitly cautions that the arms are not a like-for-like control comparison.

The registry record lists one outcome measure and no analyses. It does not report recruitment procedures, the timing of individual measurements beyond the outcome timeframe and study description, or the statistical plan. Those details are not reported in the registry record.

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.

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 Muscle Glutathione Concentration, measured over 20-weeks.

The primary endpoint is muscle glutathione concentration, measured by liquid chromatography. The record describes it as a continuous measure, with the parameter specified as a mean and dispersion specified as a standard deviation. Its unit is micromol/g.Hb, and the listed timeframe is 20-weeks.

Glutathione is the biomarker at the center of the study rationale. The brief description discusses glutathione deficiency and proposes assessing whether supplementation is followed by changes in glutathione levels. Muscle glutathione concentration therefore provides a quantitative biological measure relevant to that research question. A continuous outcome can describe both the average measured concentration and the spread of measurements among participants, when those results are reported.

The registry record does not report a baseline mean, a follow-up mean, a change estimate, a standard deviation, or a confidence interval for this endpoint. It also does not specify the primary outcome population in the corresponding field. Consequently, the endpoint definition identifies what was intended to be measured, but the record does not show the numerical result or its precision. The endpoint alone cannot establish whether a change occurred or what its clinical importance might be.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record gives a limited description of the statistical methods. It identifies the primary outcome as a continuous measure summarized by a mean and standard deviation, and it lists no analyses. It does not report the statistical plan, an analysis population, an estimate of change, a confidence interval, or a p-value. The concepts below explain how such methods are generally interpreted; they are not a description of analyses documented for this study.

What does a mean describe?

For a continuous measurement, the mean describes the average value in the observations being summarized. For this endpoint, the intended measurement is muscle glutathione concentration in micromol/g.Hb. A mean at a specified assessment can describe the level measured in a group, but by itself it does not show how measurements vary or whether the average changed from an earlier assessment. To quantify change, an analysis would need to state what measurements were compared and how the change was calculated. No such estimate is reported in the registry record.

What does the standard deviation describe?

The standard deviation describes the spread of individual measurements around their mean. It is not the same as the uncertainty in the estimated mean. A larger spread can reflect more variation among measured values, while the precision of an estimated mean also depends on the amount of usable information and the analysis method. The registry record specifies standard deviation as the dispersion measure but does not report its value.

How would a before-and-after analysis be read?

In a general paired before-and-after analysis, each participant's follow-up measurement is related to that participant's earlier measurement. An analysis of within-person changes can account for the fact that repeated measurements from the same person are related. It needs both measurements, or a stated method for handling incomplete pairs. The record describes assessments before and after supplementation, but it does not report whether a paired analysis was conducted or how missing measurements were handled.

A group-level comparison of measurements at two time points is not automatically equivalent to an analysis of individual change. The choice matters because the estimate and its uncertainty depend on the data structure and analysis. The registry record does not provide enough information to determine which approach, if any, was used.

Why does the study design matter?

Random allocation can help create comparable groups for evaluating a treatment contrast. This record states allocation is not applicable and describes a single-group model. General before-and-after comparisons can describe temporal change, but without a comparable control group they cannot, on their own, distinguish the effect of the intervention from other changes that coincide with the assessment period. The Control Arm label in the adverse-event listing does not overturn the design description or establish a valid comparison.

What do confidence intervals and p-values contribute?

In general, a confidence interval communicates uncertainty around an estimated quantity: narrower intervals indicate greater precision under the method's assumptions, while wider intervals indicate less precision. A p-value evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. Neither measure, by itself, conveys clinical importance, and neither substitutes for a clearly described design and estimand. No interval or p-value for the primary endpoint is reported in the registry record.

What is over-dispersion?

Over-dispersion is a general concern for outcomes whose observed variability exceeds what a chosen probability model expects. It can make standard errors too small and confidence intervals too narrow if the model does not account for the extra variation. The primary outcome is described as continuous and summarized by a mean and standard deviation; the record does not identify a count model or report an over-dispersion assessment. This concept is included for statistical context, not as a claim that over-dispersion affected this study.

How should planning illustrations be understood?

The planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are calculation assumptions for planning illustrations, not evidence that the trial used that design or analysis. They do not match the registry's description of a single-group model without a like-for-like control comparison. Such sample-size illustrations are not observed power. The record does not report the study's own sample-size justification, nor does it provide the primary outcome results needed to evaluate the observed effect.

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("GlyNAC", "Control Arm")
n   <- c(8, 8)
m   <- c(0.5, 2.2)
sp  <- c(0.2, 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  GlyNAC  8  0.500  0.200  0.333  0.667
CARM  Control Arm  8  2.200  0.800  1.531  2.869

11. Multiplicity, Missing Data and Analysis Populations

The brief description names multiple areas of interest, including glutathione, body composition and anthropometry, strength and function, quality of life, mitochondrial energetics, biochemistry, metabolism, cognition, and memory. The registry record lists one outcome measure, muscle glutathione concentration, and no analyses. It does not report a statistical plan for selecting outcomes, testing multiple hypotheses, or controlling the chance of false-positive findings across outcomes. Multiplicity procedures are not reported in the registry record.

In general, testing multiple outcomes or multiple time points can increase the chance that at least one result appears noteworthy by chance. A prespecified hierarchy or adjustment can address some multiplicity concerns, but the record does not identify such a plan. The description of several research aims should not be mistaken for evidence that results for each aim were collected, analyzed, or reported.

Missing-data methods and analysis populations are also not reported in the registry record. The outcome population field is blank, and no analysis is listed. The record does not say how many participants contributed primary outcome data, whether all planned assessments were completed, or how incomplete measurements were handled. Enrollment of 16 does not establish the number included in an endpoint analysis.

Without this information, the completeness and representativeness of the analyzed data cannot be assessed. Any interpretation of numerical estimates, if reported elsewhere, would need to consider the analysis population, missingness, and outcome-selection procedures. Those details 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 adverse-event listing names a GlyNAC Arm and a Control Arm. For each listed arm, the record states that 8 were at risk for serious adverse events and 0 were affected; it also states that 8 were at risk for other adverse events and 0 were affected. Deaths are listed as 0 for each arm. These are the counts as recorded, not calculated event rates.

The adverse-event arm labels need to be read alongside the design description. The registry record identifies a single-group study, says allocation is not applicable, and cautions that the arms are not a like-for-like control comparison. The listing therefore does not establish a controlled safety comparison or show that participants were randomized between GlyNAC and control.

Zero listed events means the registry record reports no affected participants in those adverse-event categories for the listed groups. It does not establish that an event was impossible or that the intervention is free of risk. The record does not provide additional detail on event definitions, collection procedures, timing, or how the listed at-risk counts relate to the enrolled population. Those details are not reported in the registry record.

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

The registry record documents a completed Phase 1 study of oral GlyNAC in people with HIV, with muscle glutathione concentration designated as the primary outcome. It describes a planned before-and-after assessment and a measurement period that includes supplementation and washout. These design details establish the research question and intended measurements, but the record does not report the primary outcome values or an analysis.

Because no numerical endpoint result is reported, the direction and size of any change in muscle glutathione cannot be described from this record. The precision of a change estimate also cannot be assessed because no standard deviation, confidence interval, or other uncertainty measure is reported. The record does not provide a result that can be compared with a threshold for clinical importance.

The single-group design further limits what a before-and-after result could establish. In general, change over time within a group is not the same as a treatment effect established against a comparable control. The Control Arm label in the adverse-event listing should not be taken as evidence that a suitable comparator was used for the primary outcome.

The study description identifies a broad range of intended areas of investigation, but the registry lists one outcome measure and no analyses. It is therefore not possible to determine from the registry record whether the other planned measures were collected or what they showed. Similarly, the completed status does not fill in missing outcome results.

The appropriate statistical reading is limited: the record describes what the study aimed to investigate and how the primary endpoint was defined, but it does not establish whether the endpoint changed, how precisely it was measured, or what any change would mean clinically.

14. Why This Trial Matters Statistically

This study is statistically instructive because the design description and the adverse-event listing do not tell the same story at first glance. The main design fields identify a single-group study with allocation not applicable, while the safety listing uses both GlyNAC Arm and Control Arm labels. Keeping design information separate from administrative arm labels is essential: the latter do not establish a valid comparator for estimating an intervention effect.

The record also illustrates why an outcome definition and an outcome result are different things. Muscle glutathione concentration is defined as the primary endpoint, with a stated unit, summary measure, dispersion measure, and timeframe. Yet no estimate or analysis is reported. Statistical interpretation requires both a clear endpoint and the data-based result, including information about its uncertainty.

The study description proposes measurements before and after supplementation and after washout. A single-group repeated-measure design can be useful for describing patterns over time. As a general principle, however, such patterns do not have the same causal interpretation as a comparison against a suitable control group. The design determines what questions a statistical contrast can answer.

Finally, planning calculations should not be confused with evidence from the trial. The record's planning assumptions use equal allocation between two arms even though the stated study model is single group. Those assumptions belong to a planning illustration, not a report of observed power or proof that the trial used a two-arm design. Clear separation of planning, design, and results helps prevent stronger conclusions than the record supports.

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 limitations specific to this record constrain statistical interpretation. The registry identifies a single-group model and no allocation, so it does not document a randomized, like-for-like control comparison. Although a Control Arm appears in the adverse-event listing, the record explicitly warns against treating the arms as a valid control comparison. This limits causal interpretation of any before-and-after change.

The registry record does not report the primary endpoint values, an effect estimate, uncertainty measures, or an analysis. It is therefore not possible to assess the magnitude, direction, or precision of the primary outcome. The outcome population field is blank, and the record does not report how many participants contributed measurements or how incomplete data were handled.

The study description includes multiple proposed domains, but the registry lists only one outcome measure and no analyses. It does not report whether all intended outcomes were measured, how outcome selection was handled, or whether a multiplicity plan was specified. The statistical plan and sample-size justification are not reported in the registry record.

The primary timeframe is listed as 20-weeks, while the narrative describes supplementation for 12 weeks or 3 months followed by a further 2 months of measurement. This describes the intended schedule but does not document completion of each assessment. Finally, the adverse-event entries provide counts without further detail on event definitions, ascertainment, or the relationship between the listed groups and the single-group design. These gaps limit the conclusions that can be drawn from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Glutathione and Function in HIV Patients — NCT02348775.
• Registry record last updated 2021-02-21; status last verified 2021-02.
• Results first posted 2021-02-21.
• 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

The registry record identifies NCT02348775 as a completed Phase 1, single-group study sponsored by Baylor College of Medicine, with enrollment of 16. It describes oral GlyNAC supplementation in people with HIV and lists muscle glutathione concentration, measured by liquid chromatography, as the primary outcome. The outcome is continuous, summarized as a mean with standard deviation, in micromol/g.Hb, with a timeframe of 20-weeks.

The description outlines supplementation for 12 weeks or 3 months and further measurement for washout. The record lists one outcome measure and no analyses. It does not report primary outcome results, a statistical plan, missing-data methods, or an analysis population. Adverse-event entries list zero affected participants and zero deaths for both named groups, but the design description cautions that the groups are not a like-for-like control comparison.