Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations (NCT02457897), a na phase 2 study. The primary outcome is Total Body Glucose Disposal in the Fasting State.

2. Clinical Question

This is a question about a physiological measure in a specific population, not a controlled estimate of how treatment compares with another treatment or with no treatment. Without a comparator, an observed change, if reported, would describe participants over the study period; it would not by itself distinguish a treatment effect from other explanations such as time-related changes or measurement variability. The registry record does not report a primary-outcome result, so even a within-group change cannot be characterized.

3. Trial Design

The study is registered as phase 2 and completed. It is a single-group study of liothyronine in people with insulin receptor mutations. Allocation is listed as NA, and masking is listed as none. No randomized control group is described. Enrollment is recorded as 7. The sponsor is the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

The registry summary describes a 19-day clinic stay. Participants were monitored for 4 days and then took thyroid hormone three times a day for 15 days. The described assessments include blood tests, monitoring of heart rate and skin temperature, controlled food provision, sessions in a special room, tracer procedures, a sweet drink, glucose monitoring, heart ultrasound, PET-CT and DEXA imaging. The summary says adults may have fat and muscle samples taken. These procedures describe the study activities; the registry record does not report their results in the material available for interpretation.

For participants with poorly controlled diabetes, the summary describes taking thyroid hormone at home for 6 months after the clinic stay. The available summary ends before giving the full details of that follow-up, so its measurements and conduct are not reported in the registry record. The primary outcome has a timeframe of 2 weeks, which identifies the stated assessment period for that outcome; it does not establish that every other assessment used the same schedule.

The registry lists muscle glucose uptake among secondary outcomes and identifies four outcome measures, but it does not provide their observed results. Nor does it give a detailed account of how the study analyzed the primary outcome. In particular, the statistical plan, handling of repeated measurements and approach to missing data are not reported in the registry record. Given the single-group design, the central interpretive limit is that no concurrent control comparison is available.

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.

Part 1 Short-term (2 Weeks) Study

Part 2 Long-term (6 Month) 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 Total Body Glucose Disposal in the Fasting State, measured over 2 weeks.

The primary endpoint is total body glucose disposal in the fasting state, expressed in μmol/kg LBM (Lean Body Mass)/min. The registry describes the measure as a mean with standard deviation and gives a timeframe of 2 weeks. In general, glucose disposal refers to the amount of glucose taken up or used by the body under the specified measurement conditions. A fasting-state measure focuses on glucose handling when participants are not described as having just consumed a meal; the registry's title and description identify the state, but do not give a detailed measurement protocol for the endpoint.

In general, a continuous physiological measure can describe the size and variability of a response, and its unit helps define how values are scaled. The lean-body-mass denominator expresses the measure relative to lean body mass rather than as an unscaled whole-body amount. The registry does not report the endpoint's observed mean or standard deviation, so there is no reported value to interpret for magnitude or dispersion. It also does not report a baseline value, a change estimate, or an uncertainty interval for this endpoint.

The endpoint is relevant to the stated research objective because the study asks about glucose handling in people with insulin receptor mutations. However, an endpoint's relevance does not establish that a treatment caused a change or that a measured change would translate into a clinical benefit. Those conclusions would require outcome results and an appropriate interpretation of the study design. Since the primary result is not reported in the registry record, the endpoint can be described but its observed behavior cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is a continuous measure, and the registry specifies a mean and standard deviation as its summary. In general, the mean describes the center of a set of measurements. The standard deviation describes how spread out individual measurements are around that center. These quantities answer different questions: the mean concerns the typical level in the measured group, while the standard deviation concerns variation among observations.

A standard deviation is not an uncertainty interval for the mean, nor is it an estimate of a treatment effect. To assess uncertainty about an effect, readers generally need an effect estimate and an accompanying measure such as a confidence interval. A confidence interval gives a range of values compatible with the data and the method used, under its assumptions. It communicates precision as well as the estimate's direction and scale. The registry record does not report the primary outcome's mean, standard deviation, effect estimate or confidence interval, so those features cannot be assessed.

What can a single-group design establish?

In general, a single-group study can describe measurements in participants who received the study intervention, including measurements taken at different times if those are collected and analyzed. A change within the group is not the same as a contrast against a concurrent control group. When no comparator is present, changes may have more than one explanation, including the intervention, time-related variation, measurement variability, or other changes during the study.

This distinction is especially important when interpreting causal language. A comparison with a control group can help separate changes associated with the intervention from changes that might also occur without it, although the strength of that inference depends on the design and analysis. No such comparison is recorded for this study. The record does not give a detailed analysis plan for any within-group comparison, so no particular test or adjustment should be assumed.

How should the outcome timeframe be read?

The registry gives the primary outcome a timeframe of 2 weeks. This identifies the stated time horizon for that measure, but it does not report the exact measurement schedule or whether the analysis compares a baseline reading with a later reading. In general, interpreting a change over time requires knowing which measurements were taken, how they were paired or summarized, and which participants contributed observations at each time. Those details are not reported in the registry record.

The outcome is expressed per kilogram of lean body mass per minute. In general, a normalized measure uses a denominator to express an amount relative to a characteristic of the participant, which can aid interpretation when body size differs. The unit does not itself tell readers how the underlying measurements were obtained, how lean body mass was assessed, or whether any adjustment was made. Those procedural and analytic details are not reported in the registry record.

Why does variability matter?

In general, variability matters because measurements from participants can differ even when they belong to the same study group. The standard deviation is one way to describe that spread for a continuous outcome. If variability is large relative to an estimated change, the data may be less precise about the size of that change. If variability is smaller, the estimate may be more precise, subject to the number of observations and the study design. This is a general statistical relationship, not a finding about this study: the endpoint's observed variability is not reported.

The registry's primary outcome is a mean with standard deviation, but it does not report an inferential test, confidence interval or model. The exact method used to estimate the mean, account for repeated observations, or quantify uncertainty is therefore not reported in the registry record. It would be inappropriate to infer a particular method from the outcome's summary type alone.

What does over-dispersion mean in general?

Over-dispersion is a general issue for certain statistical models, especially models for counts, when the observed variation is greater than the model assumes. Ignoring it can make uncertainty appear too small and can lead to overly narrow intervals or misleading tests. It is not a reported feature of this continuous primary endpoint, and the record does not state that an over-dispersion adjustment was used. This concept is included only to clarify a general statistical issue, not to describe an analysis performed in this study.

How should planning calculations be interpreted?

The registry's planning assumptions describe a hypothetical two-arm calculation using a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. They also describe detecting a stated fraction of an observed effect. These are planning assumptions, not evidence that the study itself used a two-arm design or those methods. The recorded study is single-group, and the observed endpoint effect is not reported in the registry record.

In general, a sample-size calculation estimates the number of participants needed under specified assumptions about an effect, variability, significance level and power. It is a planning tool, not a result from the completed study. Observed power should not be treated as a substitute for an effect estimate and its confidence interval. Any planning illustration based on an observed effect is likewise not observed power. Since the endpoint effect and its variability are not reported, the assumptions cannot be checked against the primary-outcome data.

The registry does not report the statistical analysis plan, the model for the primary outcome, the analysis population, or procedures for multiplicity and missing data. Those omissions prevent reconstruction of the intended analysis. General statistical concepts can explain what these methods would address, but they cannot establish which choices were made for this trial.

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("Patients With Insulin Receptor Mutation")
n   <- c(7)
m   <- c(21.47)
sp  <- c(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  Patients With Insulin Receptor Mutation  7  21.470  6.000  15.921  27.019

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcomes, including muscle glucose uptake. It also records four outcome measures. However, the statistical plan for testing or estimating those outcomes is not reported in the registry record. It does not state whether any adjustment for multiple outcomes or multiple comparisons was planned or used.

In general, multiplicity arises when several outcomes, time points or comparisons are examined. When many statistical tests are treated as independent opportunities to declare a finding, the chance of at least one apparently notable result can increase. Methods for addressing multiplicity can include prioritizing a primary outcome, adjusting significance thresholds, or interpreting secondary analyses as exploratory. These are general approaches; the registry record does not say which, if any, applied to this study.

Missing-data methods are also not reported. The record does not state whether every enrolled participant completed the primary assessment, whether any endpoint observations were unavailable, or how unavailable measurements were handled. In general, missingness can affect both the amount of information available and the interpretation of an analysis, particularly if the likelihood of missing data is related to participant characteristics or outcomes. The number enrolled does not establish the number included in the primary analysis.

The analysis population is not specified in the registry record. It is therefore not possible to determine whether the reported analysis, if available elsewhere, would include all enrolled participants, only those who completed the intervention, or another defined group. The record also does not report an intention-to-treat framework or a per-protocol framework. No assumptions about these analysis choices should be made from the registry entry alone.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 serious adverse events among 7 at risk in the group titled Patients With Insulin Receptor Mutation. It also lists 3 other adverse events among 7 at risk. These figures are reported as counts; no percentages or comparative estimates are needed to interpret them.

The counts describe recorded events in the study group. They do not establish whether an event was caused by the intervention, and they do not compare event occurrence with an untreated or alternative-treatment group. No comparator is listed in the study design. The registry record does not provide terms for the serious-event list, which is empty, and the brief summary does not give a detailed description of the 3 other adverse events. Their nature, timing and relationship to treatment are therefore not reported in the registry record.

In general, serious and other adverse events are separate reporting categories, and a count of events is not necessarily a count of people experiencing an event. The record does not explain whether the other-event count represents affected participants or events, so it should not be reinterpreted as either without further information. These safety figures are descriptive registry entries, not a comparative safety analysis.

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

The record establishes the study's main question and design: a phase 2, single-group evaluation of liothyronine in people with insulin receptor mutations, with fasting total body glucose disposal as the primary outcome. It also describes a clinic-based assessment period and additional procedures. These details explain what the study set out to examine, but they do not establish what happened to the primary measure.

The primary result is not reported in the registry record. There is no observed mean, standard deviation, change estimate or confidence interval to show the magnitude or precision of an outcome. As a result, the registry entry does not support a description of whether the measure increased, decreased or remained similar during the study. A completed status should not be read as a numerical result.

Even if a within-group change were reported, the single-group design would limit causal interpretation. Without a concurrent comparator, the observed change could not be separated from other time-related or measurement-related explanations using a treatment-versus-control comparison. The record does not describe a randomized comparison and should not be interpreted as one.

The safety counts likewise have a limited meaning. They record 0 serious adverse events and 3 other adverse events in the group, but the registry does not provide details for the other events or a comparison group. These entries do not demonstrate that the intervention caused or prevented an event.

In general, a clear interpretation of a clinical outcome requires the observed estimate, its uncertainty, the analysis population and an understanding of the design. Several of those elements are not reported in the registry record. The study's rationale and measurements can be described, but claims about treatment effect, clinical benefit or comparative safety cannot be drawn from the outcome information available in this record.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between measuring an outcome and reporting evidence about that outcome. The registry specifies a continuous primary measure, its unit, summary type and timeframe. That information defines what was intended to be measured. Yet without the observed mean, standard deviation or an estimated change, readers cannot evaluate the outcome's magnitude or precision.

The single-group design is another important feature. It can support descriptive observations within the enrolled group, but it does not offer a concurrent treatment contrast. This distinction matters because a change over time is not automatically attributable to the intervention. Design determines which questions an analysis can address, regardless of how carefully an outcome is measured.

The record also makes the boundary between planning and results relevant. The stated planning framework assumes equal allocation between two arms, while the registered study is single-group. Planning assumptions are useful only in relation to their specified design and effect assumptions; they are not observations from participants and are not evidence of the study's precision or power.

Finally, the registry's safety counts show why descriptive event reporting should not be confused with comparative inference. Counts can communicate what was recorded in the study group, but without details and a comparator they do not quantify a treatment-related difference. For clinical researchers and biostatisticians, the key statistical lesson is to keep the estimand, design, analysis and reported evidence aligned. In this record, the research question and outcome are identifiable, while the primary numerical result and key analysis details are not reported.

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 principal limitation for interpreting this specific record is the absence of the primary-outcome result. Although the endpoint is defined as total body glucose disposal in the fasting state, its observed mean and standard deviation are not reported. No change estimate or confidence interval is given, so neither the magnitude nor the precision of an outcome can be assessed.

The single-group design means there is no concurrent comparator in the registry record. It therefore cannot support a direct treatment-versus-control estimate. Any observed within-group change, if reported elsewhere, would require cautious interpretation because time-related changes and other influences could not be separated by a concurrent comparison in this design.

The record lists enrollment as 7, but it does not state how many participants contributed data to the primary outcome or define the analysis population. It also does not report missing-data methods, the statistical analysis plan, details of repeated-measure analysis, or procedures for handling multiple outcomes. The registry summary describes several study procedures, but their results and their relationship to the primary analysis are not reported.

Safety information is limited to event counts. The registry does not describe the other adverse events or provide a comparative group, and the relationship of events to treatment is not reported. The summary also describes a home-treatment period for participants with poorly controlled diabetes, but the available record does not give its full follow-up details.

These limitations concern what can be learned from the registry record; they do not establish that unreported procedures or analyses were absent from the study itself. They mean that such details are not reported in the registry record and should not be assumed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations — NCT02457897.
• Registry record last updated 2019-12-05; status last verified 2018-09-18.
• Results first posted 2019-12-05.
• 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

NCT02457897 is a completed phase 2, single-group study of liothyronine in people with insulin receptor mutations. The primary outcome is total body glucose disposal in the fasting state, expressed in μmol/kg LBM (Lean Body Mass)/min, with a timeframe of 2 weeks. The registry identifies the outcome as a mean with standard deviation.

Enrollment is recorded as 7. The study has no listed comparator, allocation is recorded as NA, and masking is listed as none. The summary describes a 19-day clinic stay, including monitoring and 15 days of thyroid hormone treatment, with an additional home-treatment period for participants with poorly controlled diabetes.

The primary outcome's observed mean, standard deviation and treatment-effect estimate are not reported in the registry record. The safety entry lists 0 serious adverse events among 7 at risk and 3 other adverse events among 7 at risk. Statistical analysis details, missing-data methods and the analysis population are not reported.