Effects of rhIGF-1 on Bone Metabolism in Adolescent Girls With Anorexia Nervosa: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of rhIGF-1 on Bone Metabolism in Adolescent Girls With Anorexia Nervosa (NCT00720122), a na phase 2 study. The primary outcome is Change in Spine Bone Density (g/cm^2).

2. Clinical Question

The registry record frames the study around bone density and bone microarchitecture in people with anorexia nervosa. Its stated rationale notes that this population may have low bone mineral density and that IGF-1 deficiency may contribute to skeletal changes. The study examined whether rhIGF-1 treatment was accompanied by a change in spine bone density over the specified follow-up period.

Because this was a single-group study, the primary question concerns change over time within the analyzed group. It is not a randomized comparison of rhIGF-1 with an untreated or alternative-treatment group. A within-group change can describe what happened among participants who met the analysis criteria, but by itself it cannot isolate the effect of the intervention from other explanations for change over time.

The registry record does not report the numerical primary endpoint result, its uncertainty, or a test of change. It therefore does not establish the direction or precision of the observed change in the posted record.

3. Trial Design

This is a completed phase 2 study sponsored by Massachusetts General Hospital. The registry record gives a planned enrollment of 28 and describes a single-group model. Allocation is listed as NA and masking as none. The listed study start is 2008-07, and the primary completion is 2011-10.

The intervention was recombinant human insulin-like growth factor-1 (rhIGF-1), recorded as a drug. The group is titled Anorexia Nervosa Females. The study summary describes investigation of rhIGF-1 over a 6 month period, and the primary endpoint compares spine bone density at baseline with the assessment at 6 months.

The primary analysis population was narrower than the enrolled group: participants had to complete the first 6 months and have bone density measured at both baseline and the 6 month visit, as per protocol. The number meeting those conditions is not reported in the registry record. Consequently, the enrolled number should not be read as the number contributing to the primary endpoint analysis.

There is no like-for-like control comparison in this design. The record does not describe a randomized allocation, a masked assessment, or a comparator group. Those features matter when interpreting change over time: without a concurrent control group, the study does not directly estimate how participants would have changed over the same period without rhIGF-1.

The registry record describes the study status as completed. The detailed protocol, the treatment schedule, and further operational details are not reported in the registry record. The record also does not give a numerical result for the primary endpoint, so the design information alone cannot establish the size or direction of the observed change.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The study participants analyzed were those that completed the first 6 months of the study and had a bone density performed at the baseline visit and then again at the 6 month visit as per protocol.

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 Change in Spine Bone Density (g/cm^2), measured over Baseline and 6 months.

The primary endpoint is change in spine bone density, expressed in g/cm^2, from baseline to 6 months. The registry defines change as the 6 month measurement minus the baseline measurement. Spine bone density was assessed using dual energy x-ray absorptiometry at both visits. The endpoint is a mean of a continuous measure, with dispersion specified as the standard error.

In general, a continuous endpoint retains the amount of change measured on its scale, rather than reducing observations to categories such as improved or not improved. A mean describes the central value of the observed changes in the analysis population. The standard error describes the precision of an estimated mean; it is not the same as the spread of individual participants’ measurements.

In general, bone density is used as a quantitative measure of bone status. A measurement at the spine provides a defined skeletal site for comparing baseline with follow-up. The registry record’s endpoint description identifies the measurement method and timing, but it does not report the resulting mean change or its standard error.

The population definition is important to interpretation: only participants completing the first 6 months with measurements at both visits were included in the stated analysis population. The number analyzed and the endpoint estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change represent?

The endpoint is a continuous measurement: each participant with both visits has a baseline and a 6 month spine bone-density value, and the registry defines the change as the later value minus the baseline value. The reported group-level quantity is intended to be the mean of those changes. In general, a mean summarizes the central tendency of observations on a numerical scale. It does not show whether every participant changed in the same direction, nor does it describe the full spread of individual changes.

The numerical mean change is not reported in the registry record. That omission prevents interpretation of the endpoint’s direction and size. The registry record also does not give participant-level measurements, so individual variation cannot be assessed.

How should the standard error be read?

The endpoint lists standard error as its dispersion measure. In general, the standard error estimates the sampling uncertainty of a group mean: smaller standard errors indicate more precise estimates under the model and assumptions used. It is distinct from a standard deviation, which describes variability among observations. A standard error alone does not show the range of individual participant outcomes.

Neither the standard error value nor a confidence interval is reported in the registry record. In general, a confidence interval pairs an estimate with a range representing its uncertainty under specified statistical assumptions. It can help readers judge which values remain compatible with the observed data. It does not remove limitations from a single-group design, and it cannot be reconstructed from the information in the registry record.

What does the single-group structure permit?

The study model is recorded as single-group, and no comparator is listed. A within-group change can describe the difference between the baseline and follow-up measurements among participants in the analysis. In general, it does not provide the counterfactual comparison needed to determine what would have happened to the same population over the same period without the intervention. A statistically precise before-and-after estimate would still not, on its own, establish a causal treatment effect.

The record lists allocation as NA and masking as none. No randomized comparison is described. The registry record does not report additional procedures or analyses that might address confounding or measurement-related concerns.

How does the analysis population affect the result?

The stated analysis population consists of participants who completed the first 6 months and had bone-density assessments at both specified visits. In general, a complete-measurement analysis can exclude participants without follow-up data. If completion or measurement availability is related to health status or outcome, the analyzed group may differ from the enrolled group in ways that affect the estimated mean change. The registry record does not report how many participants met the endpoint criteria, why any measurements were unavailable, or whether missing data were handled using additional methods.

What can planning illustrations tell readers?

Any sample-size planning illustrations are hypothetical planning calculations, not observed power. The described calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm comparison; they do not change the fact that this study is recorded as single-group. The planning values are not evidence that the study had a particular probability of detecting an effect, and they do not replace the unreported primary estimate or its uncertainty.

In general, planning calculations depend on assumptions about the effect to detect, variability, design, and analysis. If those assumptions differ from a future study, the planning result may not apply. The registry record does not report the trial’s own sample-size justification, so the planning illustrations should not be taken as the documented design rationale for this study.

What cannot be concluded from the posted result?

The registry record does not provide the mean change, standard error, confidence interval, or p-value for the primary endpoint. Therefore, readers cannot assess statistical evidence for change, its precision, or the range of values consistent with the data. General statistical principles can clarify what those measures would mean, but they cannot supply the missing result.

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("Anorexia Nervosa Females")
n   <- c(19)
m   <- c(-0.00558)
sp  <- c(0.00653)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Anorexia Nervosa Females  19  -0.006  0.028  -0.019  0.008

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 1 outcome measure and 1 analysis. It identifies change in spine bone density as the primary endpoint. A separate multiplicity adjustment or a plan for handling multiple statistical tests is not reported in the registry record. With only the listed primary endpoint and analysis available, the record does not establish whether additional outcomes or analyses were planned or conducted.

Multiplicity is a general concern when several outcomes, time points, or statistical tests are examined. More testing can increase the chance of finding an apparently notable result by chance, depending on the procedures used. A prespecified analysis plan can clarify which outcomes are primary and how testing is handled. Such a plan is not reported in the registry record.

The endpoint population is defined as participants who completed the first 6 months and had bone-density measurements at baseline and 6 months. The number analyzed, the number without endpoint measurements, and reasons for missing measurements are not reported in the registry record. Imputation methods, sensitivity analyses for missing data, and an intention-to-treat analysis are not reported in the registry record.

In general, missing-data methods rely on assumptions about why values are missing and how missing participants’ outcomes relate to observed data. A complete-measurement analysis describes the participants with both measurements; it may not represent all enrolled participants if missingness is related to outcome or participant characteristics. The registry record does not provide enough information to assess that possibility or to determine whether the primary analysis was robust to missing data.

12. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (14.3%), self-injury (3.6%).

The registry record lists 5 participants at risk for serious adverse events and 5 affected in the Anorexia Nervosa Females group, with 28 at risk. It lists 22 affected for other adverse events, also with 28 at risk. The record’s listed serious-event terms include Hospitalization at 14.3% and Self-Injury at 3.6%.

These are safety summaries for the recorded group, not a comparison with a separate control group. The registry record does not provide a comparative safety estimate. It also does not report enough detail to determine event timing, recurrence, severity beyond the serious-event classification, or whether individual participants experienced events in more than one category. The counts should not be added together to infer a number of affected participants.

Deaths are listed as null. This means deaths are not reported in the registry record; it should not be interpreted as a confirmed count of zero. The safety entries do not address the missing numerical result for the primary bone-density endpoint, and they do not establish a causal explanation for any event.

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

This study addresses a defined longitudinal question: how spine bone density changed from baseline to 6 months among participants with measurements at both visits after rhIGF-1 treatment. The registry record supplies the endpoint definition, measurement method, and analysis-population criteria. It does not report the numerical change or its uncertainty, so the posted results do not show the direction, size, or precision of the primary outcome.

The study’s single-group design also shapes what any within-group change could mean. In general, observing change over time is not the same as estimating what would have happened without the intervention. A concurrent comparator can help distinguish treatment-related change from other changes over the same period; no such group is described in the registry record. Therefore, even a reported before-and-after difference would need cautious interpretation as a descriptive change rather than a definitive causal effect.

The endpoint is measured at the spine using dual energy x-ray absorptiometry and is expressed as a continuous bone-density measure. That makes it possible to describe average numerical change, but an average would not show how outcomes varied among participants. The record does not report individual data or the number of participants included in the primary analysis.

The safety information is separate from the efficacy endpoint. It lists serious and other adverse events, but there is no comparator for interpreting differences in risk, and deaths are not reported in the registry record. These entries should be read as registry-recorded safety counts and terms, not as proof of benefit, harm, or causation.

In general, a complete interpretation would consider the effect estimate, uncertainty, analysis population, missingness, and design limitations together. Several of these elements are not reported in the registry record. The available record therefore characterizes the study question and selected safety information, but does not support a conclusion about the primary outcome’s observed result.

14. Why This Trial Matters Statistically

This study is statistically useful to consider because it illustrates the difference between measuring change and establishing a treatment effect. A baseline-to-follow-up endpoint can describe how a group’s measurements differ over time. Without a concurrent comparator, however, that change cannot by itself separate the intervention from other influences on the outcome.

The analysis population also matters. The primary endpoint applies to participants who completed the first 6 months and had measurements at both visits. The enrolled number is 28, but the number meeting that endpoint definition is not reported in the registry record. Readers therefore cannot determine how complete the primary outcome data were or whether the analyzed participants represent the enrolled group.

Precision is another essential part of an outcome report. The endpoint specifies a mean and standard error, but neither the mean change nor the standard error is reported. Without an estimate and its uncertainty, readers cannot judge how large the observed change was or how precisely it was estimated. A study’s design description and rationale cannot substitute for those outcome statistics.

Finally, planning calculations must be kept distinct from trial results. In general, a sample-size illustration answers a hypothetical planning question under stated assumptions. It does not establish observed power or show that a study detected an effect. The registry record’s planning assumptions describe a hypothetical two-arm calculation, while this trial is recorded as single-group. Keeping those concepts separate helps prevent a planning exercise from being mistaken for evidence about the observed outcome.

Together, these points show why endpoint definitions, analysis populations, uncertainty, and comparison structure all matter. The record documents some of those design features, while leaving key result and missing-data details unreported.

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 main trial-specific limitation is the lack of a comparator group. The study is recorded as single-group, with allocation listed as NA and masking listed as none. As a result, the design does not provide a like-for-like control comparison. Any baseline-to-follow-up change would not alone identify the effect of rhIGF-1 separately from other changes during follow-up.

The primary analysis population includes participants who completed the first 6 months and had bone-density measurements at baseline and 6 months. The number included is not reported in the registry record. The record also does not report the number with missing follow-up measurements, reasons for missingness, or methods used to address missing data. This limits assessment of how representative the analyzed group may be.

The numerical primary endpoint result is not reported in the registry record. Neither the mean change nor its standard error, confidence interval, or p-value is available. Consequently, the direction, magnitude, and precision of the outcome cannot be evaluated from the posted results.

The record describes spine bone density measured by dual energy x-ray absorptiometry. It does not report the numerical result for other measures of bone metabolism or bone microarchitecture in the information available for this analysis. The registry record also does not report a detailed statistical analysis plan, multiplicity procedures, or the trial’s sample-size justification.

These limitations concern both interpretation and completeness of reporting. They do not establish that an analysis or procedure was absent from the study; those details are simply not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effects of rhIGF-1 on Bone Metabolism in Adolescent Girls With Anorexia Nervosa — NCT00720122.
• Registry record last updated 2021-11-18; status last verified 2021-10.
• Results first posted 2012-02-29.
• 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

NCT00720122 is a completed phase 2, single-group study sponsored by Massachusetts General Hospital. The registry record lists planned enrollment of 28, no masking, and rhIGF-1 as the intervention. The primary endpoint is mean change in spine bone density from baseline to 6 months, measured using dual energy x-ray absorptiometry.

The primary analysis population was participants who completed the first 6 months and had measurements at both visits. The number analyzed and the numerical endpoint result are not reported in the registry record. The study has no listed comparator, so it is not a randomized like-for-like comparison.

The registry record lists serious and other adverse-event counts and two serious-event terms. Deaths are not reported in the registry record. The study’s design and endpoint are described, but the posted results do not provide the estimate and uncertainty needed to assess the primary outcome.