Role of Methane in Glycemic Control: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Role of Methane in Glycemic Control (NCT01638429), a na early/phase 1 study. The primary outcome is Stool Methanogen Levels.

2. Clinical Question

The study focuses on a proposed relationship between methane-producing gut bacteria and glucose regulation. The registry’s rationale describes prior observations linking methane-producing bacteria with weight gain and higher blood glucose, and proposes that methane could affect intestinal transit and nutrient absorption. Those statements explain the research question; they are not results from this study.

The primary outcome was stool methanogen levels, measured before treatment and after the antibiotic course. The record also describes a post-treatment classification based on breath-test methane eradication: methane eradicators and methane non-eradicators. This distinction is not a randomized comparison. It groups participants according to a response observed after treatment, so any difference between those groups would not by itself establish that treatment caused the difference.

The record does not report numerical stool methanogen results, a treatment-effect estimate, or a statistical test for the primary question. Therefore, the direction and magnitude of any change cannot be assessed from the registry record.

3. Trial Design

This completed early phase 1 study enrolled 11 participants and used a single-group model. The registry lists allocation as NA and masking as none. Thus, the design did not include a randomized allocation to treatment and control arms, and it was not masked. The listed interventions were neomycin and rifaximin, administered together to the described group of obese or overweight, prediabetic methane-positive participants.

Stool methanogen levels were measured at baseline and after antibiotic treatment. Participants underwent a 10-day course of antibiotics. Post-treatment stool samples were collected within 31 days of completing the course, with one participant receiving an exemption and completing testing within 60 days. The registry describes the primary outcome timeframe as baseline and 1-60 days following completion of antibiotic treatment.

For analysis, participants were grouped according to whether they eradicated methane on a breath test following treatment. The methane-eradicator group had N=8, and the methane-non-eradicator group had N=3. These are outcome-defined groups, not groups assigned at random before treatment. Consequently, they do not provide the same protection against confounding as a randomized comparison.

The record gives a study start of 2012-04, a primary completion date of 2014-04, and a completed status. It lists Diabetes and Obesity among the conditions. The registry does not report a separate untreated or placebo group, and the listed design does not support a direct randomized estimate of treatment versus control. Protocol details beyond the registry description, including a statistical analysis plan, 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.

Before assignment: A total of 12 subjects were consented to participate. 1 subject withdrew prior to completing the study.

Overall Study

Reasons for not completing this period:

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 Stool Methanogen Levels, measured over Baseline and 1-60 days following completion of antibiotic treatment.

The primary endpoint is stool methanogen levels, measured in colony forming units. Methanogens are the methane-producing bacteria discussed in the study rationale. Measuring their level in stool gives the investigators an outcome related to the presence of these organisms, while breath testing was used to classify participants according to methane eradication after treatment.

The endpoint was assessed at baseline and after the antibiotic course. The registry describes the primary outcome as a mean of a continuous measure, with standard deviation as the measure of dispersion. A mean describes the group’s average recorded level; a standard deviation describes how spread out individual measurements are around that average. The registry record does not give the mean or standard deviation at either assessment, nor does it report the numerical change between assessments.

The outcome is relevant to the stated research question because it measures methanogen levels before and after the intervention. However, a change in this measure would not by itself establish an effect on blood glucose, weight, or other clinical outcomes. The record’s primary endpoint is stool methanogen level, not a direct measure of glycemic control. The title and rationale concern glycemic regulation, but numerical results for that question are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary measure as a continuous outcome summarized by a mean and standard deviation. No specific statistical test or model for the primary outcome is reported in the registry record. The explanation below describes general statistical concepts, not methods confirmed to have been used in this study.

What does a mean describe?

General: A mean is an average across observed measurements. For a continuous outcome such as stool methanogen levels, it provides a compact description of the group’s recorded level. The mean alone does not show whether participants had similar values or whether a few values were unusually high or low. That is why a measure of spread is often reported alongside it.

The registry specifies standard deviation as the measure of spread. General: Standard deviation describes how dispersed measurements are around their mean. It is not the same as the uncertainty in the estimated mean. Uncertainty in a mean is commonly conveyed using a confidence interval or standard error, but neither is reported for the primary outcome in the registry record.

Why does the before-and-after design matter?

General: Repeated measurements on the same participants are related: each participant’s follow-up value is paired with that participant’s baseline value. An analysis that uses this pairing can account for within-person change. The record states that measurements were taken before and after treatment, but the statistical method used to analyze those measurements is not reported in the registry record.

A single-group before-and-after comparison has no concurrent control group to show what might have happened over the same period without the intervention. Changes may reflect treatment, natural variation, measurement conditions, or other influences. General: Randomized control groups help balance measured and unmeasured factors on average, while masking can reduce some forms of measurement or participant-expectation bias. This study is recorded as single-group, with allocation NA and masking none.

How should the methane groups be understood?

The registry separates participants according to whether methane was eradicated on a breath test after treatment. The methane-eradicator group is reported as N=8 and the methane-non-eradicator group as N=3. General: When groups are defined by a post-treatment outcome, they are not equivalent to groups randomized before treatment. Factors related to the outcome used for grouping may also relate to the endpoint. Comparing these groups can be useful descriptively, but it does not on its own estimate a causal treatment effect.

The subgroup sizes also affect precision. General: Estimates from smaller groups tend to be more variable, and the data may be compatible with a broad range of underlying values. This makes uncertainty intervals and careful qualification important. Numerical subgroup estimates and intervals are not reported in the registry record.

What is over-dispersion?

General: Over-dispersion occurs when variability in observed data is greater than a statistical model assumes. If a model understates variability, standard errors may be too small and confidence intervals too narrow. Whether over-dispersion is relevant depends on the outcome and the model. The registry record does not report a model or a dispersion assessment, so it is not possible to say whether this issue arose in the analysis.

What can planning illustrations tell readers?

General: A sample-size planning calculation estimates how many participants might be needed to detect a specified effect under stated assumptions. It is a design illustration, not evidence that an effect was observed and not a measure of the study’s observed power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. Those assumptions do not turn this single-group study into a randomized two-arm trial.

The assumptions also specify that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations are expressed as total events. Numerical planning counts are not reported in the registry record. The record does not report the trial’s own sample-size justification or establish that these illustrations formed part of its original design.

What is not available for statistical review?

The registry describes 13 outcome measures and 19 analyses, but does not report the full statistical analysis plan, the tests or models used, or how the analyses were selected. The approach to multiplicity, missing data, and analysis populations is not reported in the registry record. These omissions limit assessment of whether the reported analyses, if any, followed prespecified methods and how sensitive results might be to alternative assumptions. Because numerical primary outcome results are also absent, the effect estimate and its precision cannot be independently interpreted from this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 19 analyses. It names secondary outcomes for bowel symptoms—bloating, abdominal pain, constipation, diarrhea, and straining—and percentage stool dry weight. The full set of outcome findings is not reported in the registry record. The approach to multiplicity is also not reported in the registry record.

General: When several outcomes or analyses are considered, the probability of at least one apparently notable result arising by chance can increase. A prespecified hierarchy, adjustment method, or clear distinction between confirmatory and exploratory analyses can help readers interpret multiple results. The record does not say whether such steps were planned or used, so it is not possible to assess how multiplicity was handled.

The primary outcome description says stool methanogen levels were measured in all subjects before and after treatment, followed by grouping based on breath-test eradication. It does not state how missing or unusable measurements were handled, whether all enrolled participants were included in each analysis, or how deviations from the sample-collection timeframe were treated. These details are not reported in the registry record.

The record reports enrollment of 11 and subgroup counts of N=8 and N=3. It does not provide a separate analysis-population definition, participant flow, or outcome-specific denominators. One participant’s post-treatment sample was collected within 60 days under an exemption; the implications of that timing for analysis are not reported in the registry record. Without these details and numerical outcome results, the robustness of the analysis cannot be assessed.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists 11 participants at risk for serious adverse events and 0 participants affected. It lists 11 participants at risk for other adverse events and 2 affected. These are counts reported for the obese/overweight, prediabetic methane-positive group; the record does not provide a comparison group for interpreting them comparatively.

The serious adverse event count is not the same as a complete account of all symptoms or changes during the study. The record lists no serious adverse event terms, while its secondary outcomes include bowel symptoms. The relationship, if any, between those outcome measures and the adverse-event entries is not reported in the registry record.

Deaths are recorded as not reported in the registry record. That entry should not be read as a reported zero. The registry does not give further detail on adverse-event definitions, severity grading, timing, or attribution to treatment. The counts therefore describe what is recorded, but do not establish the cause of an event or support a comparison of safety between treatments.

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

This study addresses whether stool methanogen levels changed after a course of neomycin and rifaximin in obese or overweight, prediabetic participants who tested positive for methane. Its main value in the registry is the description of a focused, before-and-after research question and the measurement approach. The primary endpoint is directly related to methanogen levels, while breath testing was used to classify participants by post-treatment methane eradication.

However, numerical results for the primary endpoint are not reported in the registry record. There is no reported baseline or follow-up mean, standard deviation, estimated change, or confidence interval. As a result, the record does not allow readers to determine the direction, magnitude, or precision of any change in stool methanogen levels. Numerical findings for glycemic outcomes are also not reported in the registry record.

The single-group design does not include a randomized comparator. Therefore, even if a before-and-after difference were available, the design alone could not separate an intervention effect from other possible explanations for change over time. The post-treatment eradicator and non-eradicator groups do not resolve this limitation because participants were classified by a response observed after treatment, rather than assigned to groups at random.

The record does not establish an effect on weight, blood glucose, or diabetes development. Those topics appear in the rationale, but they are not the primary endpoint described in the registry. No clinical recommendation follows from the information reported. The appropriate interpretation is limited to the study’s question, design, and recorded safety counts, with the central numerical outcome findings unavailable in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the research question, endpoint, design, and results must be read together. The stated rationale concerns methane-producing gut bacteria and glycemic regulation, but the primary endpoint is stool methanogen levels. That endpoint can address a microbiological question without directly answering whether glucose regulation changed.

The study also highlights the distinction between a before-and-after observation and a controlled treatment comparison. Repeated measurement can describe change in the enrolled group, but without a concurrent control group it does not provide a direct estimate of what would have happened without treatment. The post-treatment breath-test groups add a descriptive perspective but are not randomized groups.

Statistically, the record makes clear that the primary outcome was intended to be summarized as a mean with standard deviation, and it describes the timing of measurement. Yet the numerical outcome results, uncertainty estimates, and analysis methods are not reported in the registry record. Those omissions prevent assessment of effect size, precision, or the influence of analytic choices.

The record further identifies a broader set of outcomes and analyses than the primary endpoint alone. Without a reported multiplicity strategy or a complete analysis plan, readers cannot tell how confirmatory findings were distinguished from exploratory ones. These features make the trial useful as an example of the limits of interpreting a small, uncontrolled registry record: a biologically motivated question and a defined measurement do not substitute for reported estimates and a design that supports causal comparison.

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 main limitation for interpretation is the absence of numerical primary outcome results. Although the registry specifies stool methanogen levels, the measurement scale, summary statistic, and assessment timing, it does not report the observed mean or standard deviation at baseline or after treatment, an estimated change, or an uncertainty interval. The direction and precision of the primary finding therefore cannot be evaluated.

The study is recorded as a single-group design with allocation NA and masking none. It has no randomized control comparison, which limits causal interpretation of any before-and-after change. The methane-eradicator and methane-non-eradicator groups are defined after treatment and are not randomized comparisons. Their reported sizes, N=8 and N=3, also leave limited information within the smaller group.

One participant had an exemption from the usual post-treatment collection timing and completed testing within 60 days. The record does not report whether this timing affected the analysis. Missing-data handling, outcome-specific denominators, analysis populations, and participant flow are not reported in the registry record.

The registry lists 13 outcome measures and 19 analyses, but the statistical analysis plan and multiplicity approach are not reported in the registry record. The record also does not state how measurements were analyzed or how results were adjusted, if at all. Finally, the serious adverse-event listing reports no affected participants, while deaths are not reported in the registry record; further detail on event definitions, timing, and attribution is absent. These limitations restrict both efficacy interpretation and a fuller safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Role of Methane in Glycemic Control — NCT01638429.
• Registry record last updated 2019-05-02; status last verified 2019-01.
• Results first posted 2019-05-02.
• 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

The registry record describes a completed early phase 1, single-group study sponsored by Cedars-Sinai Medical Center. It enrolled 11 obese or overweight, prediabetic participants who tested positive for methane. Participants received neomycin and rifaximin in a 10-day course, with no randomized control group and no masking.

The primary endpoint was stool methanogen levels in colony forming units, measured at baseline and after treatment. Post-treatment testing generally occurred within 31 days, with one exemption allowing testing within 60 days. Participants were classified by breath-test methane eradication after treatment: N=8 eradicators and N=3 non-eradicators.

Numerical primary outcome findings, statistical analysis methods, multiplicity handling, and missing-data procedures are not reported in the registry record. The adverse-event record lists 0 serious adverse events among 11 at risk and 2 other adverse events among 11 at risk. Deaths are not reported in the registry record.