This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Evaluation of Safety and Efficiency of Metreleptin Treatment for Patients With Multiple Symmetric Lipomatosis (MSL) (NCT05351164), a na phase 2 study. The primary outcome is Change in Truncal Adiposity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05351164 |
| Phase | Phase 2 |
| Condition | Lipomatosis, Multiple Symmetrical |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan |
| Results posted | Yes |
2. Clinical Question
Population
Patients with multiple symmetric lipomatosis (MSL) who are homozygous for MFN2 R707W. The registry record lists an enrollment of 4.
Intervention
Metreleptin, administered over a 6 month intervention period. The registry record describes assessment of body composition, metabolic parameters and safety.
Comparator
There is no concurrent comparator group. The study is described as single-group, with allocation recorded as not applicable and masking as none.
Primary question
What change in truncal adiposity, measured as percentage of truncal body fat, is observed from baseline to Week 24 during metreleptin treatment?
This is a question about change over time within a small treated group, rather than a comparison of metreleptin with another treatment or with no treatment. The primary measure uses dual-energy X-ray absorptiometry (DEXA) at baseline and Week 24. The registry record describes the outcome as change in the percentage of fat tissue from the trunk area in relation to total body fat.
The study also describes assessment of metabolic parameters and safety. The available record does not report numerical results for the primary endpoint or identify the specific metabolic parameters assessed. The posted safety figures report adverse-event counts, which are considered separately below.
The study concerns a specific genetic characteristic, homozygous MFN2 R707W. Its results, even if fully reported, would therefore address this enrolled group rather than automatically describing all people with MSL. With no control group, observed changes cannot by themselves establish how the outcome would have changed over the same period without metreleptin.
3. Trial Design
This is a phase 2, single-group study of metreleptin in patients with MSL. The registry record lists an enrollment of 4, allocation as not applicable, and masking as none. It names the University of Michigan as sponsor. The study status is active, not recruiting.
The listed intervention is the drug metreleptin. The brief summary describes participants as homozygous for MFN2 R707W and states that body composition, metabolic parameters and safety are assessed during a 6 month intervention period. Additional safety assessment is described for 1 more year, up to 1.5 years total, with adverse-event data collected during that period.
The primary completion date is 2024-04-08, and the start date is 2023-08-01. These dates describe the registry record; they do not establish that every planned assessment was completed or that all results were posted. The record lists no like-for-like control comparison. Consequently, the study design can describe changes and events observed among treated participants, but it does not provide a concurrent basis for separating treatment-associated changes from other changes over time.
There is no information in the registry record about the metreleptin dose, treatment schedule, eligibility criteria beyond the stated genetic characteristic and condition, or adherence. Further detail about procedures or the analysis plan is not reported in the registry record. Those omissions limit what can be inferred about how treatment was delivered and how the analysis was conducted.
The sample-size section on this page is a planning illustration based on the observed effect, not a description of the trial’s original design. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are assumptions for an illustration, not evidence that the trial itself had two arms or used those design choices. The registry record does not report its own sample-size justification.
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
| Stage | Patients With MSL |
|---|---|
| STARTED | 4 |
| COMPLETED | 4 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Patients With MSL |
|---|---|---|
| Participants analysed | 4 | |
| Age, Continuous | years | 38.5 (SD 19.3) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Truncal Adiposity, measured over Baseline, Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage of truncal body fat |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in truncal adiposity, measured as percentage of truncal body fat. The registry record says a dual-energy X-ray absorptiometry (DEXA) scan was used at baseline and Week 24. It describes the outcome as change in the proportion of total body fat represented by fat tissue in the trunk area.
This measure focuses on body composition in a specified region rather than body weight alone. In general, a regional body-composition measure can describe whether the distribution of fat changes over time. That makes it relevant to a study assessing body composition, but the endpoint is still a measurement rather than a direct measure of how a participant feels or functions.
The endpoint is summarized as a mean with standard deviation. In general, the mean describes the average change across participants, while the standard deviation describes how dispersed individual changes are around that average. Neither quantity is reported numerically in the registry record here, so the magnitude and variability of the observed change cannot be assessed from this record.
The timing connects the endpoint to the intervention period: baseline is the starting measurement, and Week 24 is the follow-up measurement. The registry record does not report how many participants had usable DEXA measurements at both time points, how missing measurements were handled, or whether any additional measurement procedures were used. Without the numerical result and those details, the endpoint’s observed direction, size and precision remain unclear.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central limitation for interpretation is that the numerical primary-endpoint result is not reported in the registry record. Although the outcome and measurement schedule are described, the record does not give the mean change in truncal adiposity, its standard deviation, or an uncertainty interval. The direction and magnitude of the observed change therefore cannot be evaluated. The same applies to the metabolic parameters mentioned in the study summary: their numerical results are not reported in the registry record.
The study’s single-group structure also matters. It can describe what was observed in the participants who received metreleptin, but there is no concurrent control group to show what would have happened over the same period in otherwise comparable participants without the intervention. A change from baseline is not, by itself, an estimate of a treatment effect relative to an alternative. Time, measurement variation, changes in other care, or other influences could also contribute to within-group change; the registry record does not describe these factors.
The enrollment of 4 makes the amount of information especially limited. In general, a small group gives an imprecise picture of the range of individual responses, and a group mean can be sensitive to the experience of each participant. The registry record does not provide an uncertainty interval for the primary result, so its precision cannot be judged directly. The absence of a reported result is not evidence that the change was zero, nor does it indicate whether the observed change was large or small.
For safety, the registry lists 0 serious adverse events and 0 deaths among 4 participants at risk. It also lists 4 participants at risk for other adverse events and 4 affected. These are descriptive counts from a small group, not a comparison of risks between treatment groups. They do not establish that serious events cannot occur, and they do not quantify how the safety experience compares with another treatment or with no treatment.
The sample-size illustrations elsewhere on the page are planning calculations, not observed power. They use the observed effect as a basis and state assumptions about a hypothetical two-arm design. They should not be read as a reason the trial enrolled 4 participants, as a substitute for a reported uncertainty interval, or as evidence that the primary result is conclusive. The trial’s own statistical plan and sample-size justification are not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is continuous: it records a numerical amount of change in truncal body fat rather than assigning participants to a category such as improved or not improved. The registry record identifies the summary as a mean and standard deviation. In general, the mean is a measure of the center of a set of observations. The standard deviation describes how much individual observations vary around that center. They answer different questions: the mean describes the average change, while the standard deviation describes the spread of participant-level changes.
For a within-group change outcome, the relevant observations are measurements at baseline and Week 24 for the treated group. A mean change summarizes the average difference between those time points, but it does not show whether all participants changed similarly. A standard deviation helps convey that variability, although with a very small enrollment it may itself be uncertain. The numerical mean and standard deviation for this outcome are not reported in the registry record, so these features cannot be examined for the posted trial result.
In general, a confidence interval expresses uncertainty around an estimated quantity. A narrower interval indicates greater precision under the analysis assumptions; a wider interval indicates less precision. It is not a range that guarantees where an individual participant’s value lies. No confidence interval for the primary endpoint is reported in the registry record. Without an interval or other uncertainty measure, readers cannot assess the statistical precision of the mean change from the posted record.
There is no concurrent control group, so the principal design contrast is change over time within the treated group. Such a contrast can be informative descriptively, but it is not the same as a randomized comparison. General statistical caution applies: a before-and-after difference can reflect treatment, the passage of time, changes in other circumstances, measurement variability, or a combination of influences. A control group can help distinguish treatment-associated differences from background change, but this study does not include one.
The registry record describes no masking. In general, masking can reduce the influence of expectations on some aspects of trial conduct, assessment, or reporting. The potential importance depends on the outcome and the procedures used. Here, the primary endpoint is based on DEXA measurement, but the registry record does not describe assessor masking or other safeguards. It is therefore not possible to determine from the record how outcome measurement was protected from knowledge of treatment.
The planning illustrations on this page are based on the observed effect and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. In general, a sample-size calculation asks how many participants a hypothetical design would require under stated assumptions to detect an effect of a specified size with a chosen level of statistical power. Changing the assumed effect or other design features changes the resulting planning estimate. The registry record does not report the trial’s own sample-size justification, and the illustrative assumptions should not be mistaken for the design of this single-group study.
These sample-size calculations are not observed power. Observed power is not a useful replacement for the estimated effect and its uncertainty: a planning illustration cannot show whether the trial’s actual result is precise, clinically important, or reproducible. The primary numerical result is absent here, and the record does not report a confidence interval or a full inferential analysis. The illustrative sample-size display should therefore be read as a hypothetical design aid rather than as evidence about what the trial established.
The record does not report the statistical model, any adjustment variables, the handling of repeated measurements, or the approach to missing outcome data. It also does not describe distributional checks. General statistical methods may use assumptions about the distribution of measurements; those assumptions cannot be assessed without the analysis details and participant-level information. The registry record’s description of a mean and standard deviation alone does not identify the method used to estimate or test change.
Over-dispersion is a general issue when count outcomes vary more than a chosen count model expects. It can make standard errors too small if ignored. That concept is relevant to some event-count analyses, but the registry record does not provide an adverse-event model or report a comparative event-rate analysis. The safety figures are counts of participants with events, so they should be read descriptively rather than as results from a model of event frequency.
Finally, precision and causal interpretation are separate issues. More precise measurement of change would not create a control group, and a control group would not guarantee precise estimates in a small study. For this trial, the record lacks the primary numerical result and uncertainty estimate, while the single-group design limits causal comparison. The numerical tables and plots on the page should be considered alongside these design constraints, not as a substitute for information that the registry record does not report.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical plan for handling multiplicity. The study summary mentions body composition, metabolic parameters and safety, while the record identifies change in truncal adiposity as the primary outcome. It does not describe whether additional outcomes were designated as secondary or exploratory, whether multiple comparisons were planned, or whether any adjustment was used. Without that information, the risk of selectively emphasizing among several analyses cannot be assessed from the record.
Missing-data methods are also not reported in the registry record. The description identifies DEXA measurements at baseline and Week 24, but does not state how participants with a missing scan or incomplete follow-up were handled. The enrollment is 4, but the number contributing to the primary analysis is not reported. It is not possible to assume that every enrolled participant contributed complete measurements.
The analysis population is not described. The registry record does not say whether analyses included all enrolled participants, only participants who received treatment, or only those with available measurements. It does not report a protocol-defined population or explain how treatment discontinuation would affect analysis. These details matter because exclusions or missing outcomes can change the group represented by an estimate, especially in a small study.
For the same reasons, the absence of a reported primary result should not be interpreted as evidence of no change. The record does not provide enough information to determine whether the endpoint was analyzed as planned, whether any observations were excluded, or how incomplete data affected the estimate. These elements are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Patients With MSL | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Patients With MSL | 0 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Patients With MSL | 4 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patients With MSL |
|---|---|---|
| viral and non-serious bacterial infections | Infections and infestations | 3 of 4 |
| Diarrhea or nausea | Gastrointestinal disorders | 2 of 4 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 2 of 4 |
| fall from recreational vehicle | Injury, poisoning and procedural complications | 1 of 4 |
| weight loss | Metabolism and nutrition disorders | 1 of 4 |
| planned orthopedic surgery | Surgical and medical procedures | 1 of 4 |
| palpitations and chest discomfort | Cardiac disorders | 1 of 4 |
| less stamina and strength | General disorders | 1 of 4 |
| Hematuria (self resolved) | Renal and urinary disorders | 1 of 4 |
| high blood pressure | Blood and lymphatic system disorders | 1 of 4 |
The registry record reports safety counts for the group titled Patients With MSL. For serious adverse events, 4 participants were at risk and 0 were affected. For other adverse events, 4 participants were at risk and 4 were affected. The record lists 0 deaths. These are participant counts, not counts of the total number of event episodes.
In general, an “at risk” count indicates the group considered for that safety category, while an “affected” count indicates participants recorded as having an event in that category. The figures do not describe the event types for other adverse events, their severity, timing, duration, or relationship to metreleptin. Serious adverse-event terms are not listed in the registry record, consistent with the posted count of 0 affected participants in that category.
Because the group includes only 4 participants, these counts provide a limited description of safety in the trial. The absence of recorded serious adverse events or deaths in this group does not rule out such events in a larger or different population. There is no control group for comparison, and the figures do not estimate comparative risk. The registry record describes additional safety collection for 1 more year, up to 1.5 years total, but the safety counts alone do not show the timing or completeness of follow-up for each participant.
12. What the Result Does, and Does Not, Mean
This record describes a phase 2 study that assessed metreleptin in a single group of patients with MSL who were homozygous for MFN2 R707W. Its primary endpoint was change in truncal adiposity from baseline to Week 24, measured by DEXA. The registry record also describes assessment of metabolic parameters and safety over the intervention and additional safety follow-up.
The primary numerical outcome is not reported in the registry record. As a result, this page cannot establish from the posted record whether the average truncal-adiposity measure increased, decreased or remained similar, or how variable individual changes were. There is no reported confidence interval to show the precision of an estimate. Numerical results for the metabolic parameters are also not reported in the registry record.
Even if a within-group change were available, this design would not show what would have occurred over the same period without metreleptin. The absence of a concurrent comparator makes it difficult to attribute any change to the intervention rather than to other influences over time. The enrollment of 4 also means the observations represent a very small group and may not capture the range of experiences in people with MSL.
The safety counts are descriptive: 0 serious adverse events and 0 deaths were reported among 4 participants at risk, while 4 participants at risk were affected by other adverse events. These figures do not establish comparative safety or rule out events not observed in this group. Details of the other adverse events are not reported in the registry record.
The sample-size display is a planning illustration, not evidence of observed power or proof that the trial was adequately powered. It uses an assumed hypothetical design, whereas the trial itself is single-group. Taken together, the record outlines the study question and some safety counts, but does not report the primary endpoint result or enough analysis detail to judge its magnitude, precision, or causal interpretation.
13. Why This Trial Matters Statistically
This study illustrates why the design and the reported outcome both matter when interpreting a clinical trial. A before-and-after measure can describe change within participants, but without a concurrent comparator it cannot isolate the contribution of treatment from other changes over time. That distinction is important even when the outcome is measured with a defined instrument such as DEXA.
The trial also has a very small enrollment: 4 participants. In general, small studies can provide early descriptive information, but estimates may be imprecise and the experience of each participant can have a substantial influence on a group summary. A mean and standard deviation would help describe the observed change and its variability, while an uncertainty interval would help readers judge precision. Those primary numerical results are not reported in the registry record.
The study’s focus on patients with MSL who are homozygous for MFN2 R707W defines a specific group. This can make the question focused, but it also limits how readily findings could be applied to people with different characteristics. The record’s description of a 6 month intervention and extended safety collection shows that body composition and safety were considered on different timelines, though the available safety counts do not provide event timing or detailed event descriptions.
Finally, the planning illustrations and trial results answer different questions. A sample-size illustration explores the requirements of a hypothetical design under assumptions. It does not replace a reported effect estimate, uncertainty interval, or a suitable comparison. This trial is statistically informative as an example of how a small, uncontrolled study can frame a focused question, while the missing outcome results and design constraints sharply limit conclusions from the registry record.
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 most direct limitation is that the registry record does not report a numerical result for the primary endpoint. Without the mean change, standard deviation, or uncertainty interval, readers cannot assess the observed magnitude, direction, variability, or precision of change in truncal adiposity. Numerical results for the metabolic parameters described in the study summary are also not reported in the registry record.
The single-group design has no concurrent control. Any observed change from baseline could reflect influences other than metreleptin, and the record cannot estimate a difference against an alternative group. Masking is listed as none. The record does not describe assessor masking or other procedures that might reduce the influence of expectations on measurement or study conduct.
The enrollment is 4, limiting how much can be learned about variability across participants and how representative the observations may be. The population is specific to MSL with homozygous MFN2 R707W, so results would not automatically generalize to all people with MSL. The registry record does not report the number with complete primary-endpoint measurements or explain missing-data handling and analysis populations.
Other details that could clarify interpretation are not reported in the registry record, including dose, treatment schedule, adherence, eligibility criteria beyond the stated condition and genetic characteristic, and the statistical model. The record also does not give the study’s own sample-size justification or a multiplicity plan. For safety, event details and timing are not reported, and the small group cannot provide a strong basis for comparing risks. These limitations apply alongside the absence of the primary result, rather than replacing it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Safety and Efficiency of Metreleptin Treatment for Patients With Multiple Symmetric Lipomatosis (MSL) — NCT05351164.
- Registry record last updated 2025-06-12; status last verified 2025-06.
- Results first posted 2025-06-12.
- 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.
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18. Record Summary
The registry record describes a phase 2, single-group, unmasked study of metreleptin in patients with MSL who are homozygous for MFN2 R707W. Enrollment is listed as 4, and the primary endpoint is change in truncal adiposity, measured by DEXA from baseline to Week 24 and summarized as a mean with standard deviation. The study summary describes a 6 month intervention period and additional safety assessment for 1 more year, up to 1.5 years total.
The study status is active, not recruiting. The start date is 2023-08-01, and the primary completion date is 2024-04-08. The primary numerical result and metabolic-parameter results are not reported in the registry record. Safety counts list 0 serious adverse events, 0 deaths and 4 participants affected by other adverse events among 4 at risk. There is no comparator group, and the registry record does not report the trial’s statistical plan, missing-data methods, or sample-size justification.