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 Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection) (NCT01253317), a na phase 1 study. The primary outcome is Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01253317 |
| Phase | Phase 1 |
| Condition | Rett Syndrome |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boston Children's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns children with Rett syndrome. The registry summary describes eligibility as female children aged 2 to 12 with a genetic diagnosis of Rett syndrome involving an MECP2 deletion or mutation. The registry enrollment was 12.
Intervention
Participants received open-label rhIGF-1, also called mecasermin. The record describes escalating twice-daily doses over 4 weeks, followed by an option to continue at 120 µg/kg BID for 20 weeks in the OLE.
Comparator
There was no concurrent control group. The registry classifies the study as single-group, with allocation not applicable and no masking. Comparisons over time, if made, would not be comparisons against a randomized control group.
Primary question
The primary outcome is adverse events, recorded during the MAD and OLE periods. The registry also describes study goals involving safety and vital signs, and lists secondary outcomes involving apnea index and social avoidance. The record does not report an efficacy comparison or a statistical analysis of those outcomes.
3. Trial Design
This was a Phase 1, open-label, single-group study sponsored by Boston Children's Hospital. The registry lists Rett syndrome as the condition, enrollment of 12, and study status as completed. The recorded study dates are a start in 2010-12 and primary completion in 2012-09. No randomized allocation or masking is reported; allocation is listed as not applicable.
The intervention was rhIGF-1. The arm description specifies escalating twice-daily doses over 4 weeks: 40 µg/kg, 80 µg/kg, and 120 µg/kg. It then describes continued treatment at 120 µg/kg BID for 20 weeks should participants choose to enroll in the OLE. This description distinguishes the MAD period from optional OLE participation; the registry record does not provide further details about how participants entered or completed those periods.
The primary outcome is titled Adverse Events. Its timeframe is biweekly during the MAD and every five weeks during the OLE. The outcome description says that a subject with the same adverse event more than once is counted only once, using the event with the closest relationship to study medication. The registry lists secondary outcomes concerning change in apnea index and change in ADAMS social avoidance subscale scores, both across the OLE. It does not report the statistical plan, analysis populations, or outcome-analysis results for these secondary measures.
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 | Open-label IGF-1 Treatment |
|---|---|
| STARTED | 12 |
| COMPLETED | 10 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Open-label IGF-1 Treatment |
|---|---|
| Adverse Event | 2 |
Analysis population for the primary outcome, as defined in the registry: Subjects that had the same adverse event more than once are counted only one time using the closest relationship to study medication.
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.
Population: Twelve girls with MECP2 mutations participated in the 4-week MAD period; ten of them continued and completed the subsequent 20-week OLE. Nine subjects met full diagnostic criteria for RTT, all of whom continued in the OLE.
| Characteristic | Unit | Open-label IGF-1 Treatment |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 12 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| 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 | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Adverse Events, measured over biweekly during the MAD and every five weeks during the OLE.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of adverse events. The registry specifies repeated safety monitoring during the MAD and OLE periods, with different reporting intervals for the two periods. Its counting rule prevents repeated reports of the same event in one subject from being counted repeatedly; when an event recurs, the record says to use the occurrence with the closest relationship to study medication.
In general, adverse-event monitoring is used to describe the types and frequency of undesirable medical occurrences during a study. Such monitoring can characterize what was observed while participants received an intervention, but by itself it does not establish that the intervention caused an event. An uncontrolled study has no concurrent comparison group to show how event experience might differ without the study treatment.
The posted results describe participants with serious and other adverse events and identify respiratory distress among the serious-event terms. They do not provide a complete event-by-event account in the record, nor do they report an inferential analysis of the primary outcome. The endpoint should therefore be read as a safety description, not as a comparative estimate of treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes an open-label study in one group, not a randomized comparison. Its posted adverse-event results report 1 participant with a serious adverse event and 12 with other adverse events in the Open-label IGF-1 Treatment group. Respiratory distress is listed as a serious adverse-event term at 8.3%. These figures describe events recorded in the study; they do not establish whether the intervention caused them.
The primary outcome uses a rule that counts a repeated event in the same subject only once, selecting the occurrence judged closest in relationship to study medication. This means the count is not necessarily a count of every episode or every report. The record does not explain how seriousness or relationship was determined, and it does not provide further event-level details beyond the listed term and percentage.
No control group is available for interpreting event frequency against an untreated or differently treated group. General statistical interpretation: a single-group event count can describe what occurred among participants under observation, but it cannot separate treatment-associated risk from the background occurrence of illness-related events, other exposures, or chance. The open-label design also means that participants and study personnel were not masked, as indicated by the registry record; the record does not describe procedures to limit any resulting influence on reporting or assessment.
The registry lists four outcome measures and zero analyses. It does not report a statistical test, confidence interval, adjusted estimate, or analysis of change for the outcomes listed. The absence of a reported analysis should not be interpreted as evidence of no change or no effect. Likewise, the listed adverse-event results alone do not answer whether vital signs, apnea index, or social avoidance changed during treatment.
The study's stated aims include evaluating safety and effects on vital signs. Those aims describe questions the investigators intended to examine, not findings. The record does not report the results needed to assess those questions. The secondary outcome titles refer to changes from pre-OLE to post-OLE, but the corresponding estimates and their uncertainty are not reported in the registry record.
Any planning illustration based on an observed effect should be interpreted as a hypothetical design calculation, not as evidence that the study had a particular probability of detecting an effect. The stated assumptions involve two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. They do not change the actual single-group design or supply a control-group result.
9. Statistical Methods Explained
What does a single-group design show?
The study is classified as single-group, with no masking and allocation listed as not applicable. Participants received open-label treatment, and no concurrent control group is described. In general, a single-group study can document measurements and events observed during treatment. Without a control group, however, observed changes cannot be cleanly distinguished from changes that might have occurred over time for other reasons. This limits causal interpretation even when measurements are collected repeatedly.
The treatment description includes dose escalation during the MAD and an optional OLE. Repeated measurement can help describe how outcomes vary over time, but the registry record does not report the analysis method used to compare measurements across periods. It also does not report whether all enrolled participants contributed data at each assessment.
How should adverse-event counts be read?
The primary outcome is a count of adverse events, with a rule to count a subject only once for the same event and retain the occurrence closest in relationship to study medication. In general, this kind of rule makes the reported count different from a count of all episodes. It also makes clear that a participant-level count, an event-level count, and a rate over time answer different questions. The registry's result reports participants affected and a serious-event term, rather than a detailed set of event rates with time at risk.
General statistical explanation: rare events can be estimated imprecisely, especially in a small study, and a percentage alone does not describe the full uncertainty around an estimate. The registry record does not provide confidence intervals for the serious-event result. It also does not give enough information to reconstruct event-specific exposure time or compare rates across treatment periods.
What do confidence intervals and tests add?
General explanation: a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical model. A hypothesis test evaluates how compatible observed data are with a stated null model. Neither can be interpreted without knowing the analysis population, outcome definition, model, and handling of missing data. The registry record does not report a confidence interval, a test statistic, or a statistical model for the posted adverse-event results. It lists zero analyses.
The record's sample-size assumptions describe a planning illustration based on an observed effect, not the original trial design. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. In general, such calculations ask how many participants per arm might be needed under assumed conditions. They are not observed power, do not demonstrate that the study was adequately powered, and do not turn this single-group study into a two-arm comparison. The registry record does not report the original sample-size justification.
Why does over-dispersion matter in general?
General explanation: count outcomes can vary more widely than a simple statistical model assumes. This is called over-dispersion. If it is present and not accounted for, standard errors and uncertainty estimates may be misleading. Whether over-dispersion is relevant depends on the count definition and the analysis model. The registry record does not report a count model or any assessment of over-dispersion, so it is not possible to say whether it was evaluated.
What can be concluded from the reported methods?
The record gives the outcome name, the monitoring schedule, and a rule for counting repeated adverse events. It does not provide the full statistical analysis plan, methods for handling repeated measurements, procedures for missing observations, or analysis populations. These omissions mean that the inferential properties of any unreported analyses cannot be assessed from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures and zero analyses. It identifies Adverse Events as the primary outcome and lists secondary outcomes concerning apnea index and ADAMS social avoidance scores. It does not report a statistical analysis plan or explain how the outcomes were prioritized beyond identifying the primary outcome. A multiplicity adjustment, testing hierarchy, or strategy for interpreting multiple outcome tests is not reported in the registry record.
Multiplicity is a general statistical concern when several outcomes or comparisons are tested: the chance of obtaining an apparently notable result by chance can increase across a family of tests. Whether and how that concern was addressed cannot be determined because the record does not report inferential analyses or a multiplicity procedure. The number of outcome measures alone does not establish that every measure was tested.
The registry record does not report how missing data were handled, whether observations were excluded, or how participants who did not continue into the OLE were treated in analyses. It also does not define an intention-to-treat, per-protocol, safety, or other analysis population. The enrollment and adverse-event results do not fill in those methodological details. As a result, the representativeness of reported outcomes and the effect of missing observations cannot be evaluated from the record.
For the primary adverse-event measure, the record specifies how repeated instances of the same event in one subject are counted. That rule does not explain how missing safety reports or incomplete follow-up were addressed. The absence of these details should be treated as unreported methods, not as proof that data were complete or that missingness had no influence.
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 |
|---|---|---|---|
| Open-label IGF-1 Treatment | 1 | 12 | 8.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Open-label IGF-1 Treatment | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Open-label IGF-1 Treatment |
|---|---|---|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Open-label IGF-1 Treatment |
|---|---|---|
| Polydipsia | Endocrine disorders | 6 of 12 |
| Snoring | Respiratory, thoracic and mediastinal disorders | 5 of 12 |
| Precocious puberty | Reproductive system and breast disorders | 4 of 12 |
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | 2 of 12 |
| Tonsillar Hypertrophy | Respiratory, thoracic and mediastinal disorders | 2 of 12 |
| Vomiting | Gastrointestinal disorders | 2 of 12 |
| Salivary hypersecretion | Gastrointestinal disorders | 2 of 12 |
| Nonscarring hair loss | Skin and subcutaneous tissue disorders | 2 of 12 |
Serious events with the highest arm-level rate: respiratory distress (8.3%).
The Open-label IGF-1 Treatment group lists 1 participant with a serious adverse event and 12 participants with other adverse events. Respiratory distress is listed among the serious adverse-event terms at 8.3%. The primary outcome description says that repeat occurrences of the same event in a subject are counted once, using the occurrence judged closest in relationship to study medication.
These results describe recorded events during the study; they do not establish that rhIGF-1 caused an event. There was no concurrent control group, and the registry does not report a comparison with background event frequency. The listed percentage is a descriptive result, not a comparative risk estimate. The record does not report a confidence interval for it.
The serious-event count and the other-event count represent different categories and should not be added together. The record does not provide a complete breakdown of all event terms, event episodes, duration, or participant-level follow-up. It also does not report the method used to assess seriousness or medication relationship. Accordingly, the figures are best read as a limited summary of safety observations rather than a full account of the safety profile.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase 1, open-label, single-group study of rhIGF-1 in Rett syndrome was completed, with registry enrollment of 12. It describes escalating doses and an option to continue treatment in the OLE. It also reports adverse-event observations, including 1 participant with a serious adverse event, 12 with other adverse events, and respiratory distress listed as a serious-event term at 8.3%.
These observations are descriptive. With no randomized control group, they cannot show how outcomes would have differed without treatment or under another treatment. An event occurring during a study does not by itself establish causation. The record's event-counting rule also means its summary should not be read as a count of every repeated episode.
The registry states that investigators aimed to assess safety and vital signs and lists secondary outcomes involving apnea index and social avoidance. It does not report outcome estimates or analyses for those questions. Therefore, the record does not establish whether these measures changed, how precisely they were measured, or whether any change can be attributed to treatment. Not reporting an analysis does not mean that an outcome was unchanged.
Any sample-size planning illustration based on an observed effect is hypothetical and uses assumptions for a future two-arm comparison. It is not observed power and does not provide evidence of efficacy. The registry record does not report the original sample-size justification, statistical analysis plan, handling of missing data, or analysis populations. Those omissions constrain how far the posted results can be interpreted.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between documenting events and estimating comparative effects. Its open-label, single-group structure permits description of observations during treatment, but it does not provide a concurrent counterfactual. As a result, safety counts can signal what was reported without quantifying how much risk is attributable to treatment relative to another condition.
The primary outcome's rule for repeated events also matters. Counting a subject once for the same event, rather than counting every occurrence, changes the interpretation of the outcome. Readers should distinguish participant counts from event counts and avoid treating the listed summary as a complete tally of all episodes.
The record also illustrates why outcome titles and study aims are not equivalent to analyzed findings. Although vital signs, apnea index, and social avoidance appear among the study goals or outcomes, the registry lists zero analyses and does not report estimates for them. Without estimates and uncertainty, the magnitude and precision of any change cannot be assessed.
Finally, a planning calculation based on an observed effect is not a substitute for a prospective design justification or a controlled result. The stated planning assumptions describe a hypothetical two-arm setting, while the actual study is single-group. Keeping those roles separate avoids interpreting a design illustration as evidence about the effect of rhIGF-1.
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 lack of a concurrent control group. The registry classifies the study as single-group and open-label, so observed events and any within-study changes cannot be separated from background occurrence, time trends, or other influences through a randomized comparison. The record does not report masking or a control condition.
The posted safety summary is limited. It identifies the number of participants with serious and other adverse events and lists respiratory distress as a serious-event term, but does not provide a detailed event-level account, confidence intervals, or a comparative analysis. The registry's rule for repeated events also means that the summary is not a count of every episode.
The registry lists secondary outcomes but does not report their results or analyses. It lists zero analyses, and does not report the statistical plan, multiplicity handling, missing-data methods, or analysis populations. This prevents assessment of how outcome estimates were produced or how incomplete observations may have affected them.
The intervention description includes dose escalation and optional OLE participation, but the registry record does not report further details on continuation, adherence, or participant flow across periods. The original sample-size justification is not reported. Any planning illustration based on observed effects is a hypothetical design calculation, not a substitute for these missing design and analysis details.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection) — NCT01253317.
- Registry record last updated 2017-06-22; status last verified 2017-06.
- Results first posted 2017-06-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01253317 is a completed Phase 1 study titled Treatment of Rett Syndrome With rhIGF-1 (Mecasermin [rDNA]Injection). Boston Children's Hospital is listed as sponsor. The registry records a start in 2010-12, primary completion in 2012-09, and enrollment of 12.
The study used open-label rhIGF-1 in a single group, with no randomized allocation or masking. The intervention description specifies twice-daily dose escalation over 4 weeks and optional continued treatment in the OLE. The primary outcome is Adverse Events, monitored biweekly during the MAD and every five weeks during the OLE, with a rule to count repeated instances of the same event in a subject once.
The posted safety results list 1 participant with a serious adverse event, 12 with other adverse events, and respiratory distress among serious-event terms at 8.3%. The registry lists four outcome measures and zero analyses. Results for the listed secondary outcomes and further statistical methods are not reported in the registry record.