Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears (NCT02420353), a randomized phase 2 study. The primary outcome is Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op.

2. Clinical Question

The clinical rationale in the record is that ACL injury can be followed by muscle atrophy and strength loss. The study considered whether somatropin, acting on the growth hormone and insulin-like growth factor-1 axis, might help preserve or restore muscle strength. Those statements describe the rationale, not a demonstrated effect of treatment.

The primary endpoint was not a direct measure of muscle size, return to activity, reinjury, osteoarthritis, or quality of life. It was a strength measurement expressed relative to the participant's uninjured limb before surgery. This makes the endpoint a specific functional measure at a specified postoperative time, rather than a comprehensive assessment of recovery.

The registry record reports arm-level means and confidence intervals and a p-value from a mixed models analysis. It does not report a model-based treatment-effect estimate or its confidence interval. The findings therefore need to be read as a comparison of the posted strength summaries and the reported statistical test, with uncertainty and the endpoint's limited scope kept in view.

3. Trial Design

The registry record describes a completed phase 2 randomized, triple-masked, parallel-group trial sponsored by the University of Michigan. Enrollment was 20. The listed interventions were somatropin and placebo; the primary endpoint analysis included 19 participants. The record does not report why the number analyzed for this endpoint was smaller than enrollment, or whether the difference reflects missing measurements, exclusions, or another reason.

A parallel-group design assigns participants to a treatment group that is compared with a separate group assigned to the comparator. Random allocation can reduce systematic differences between groups on average, although it does not guarantee that every participant or prognostic characteristic is balanced, particularly in a small trial. The method used to generate or conceal the allocation sequence is not reported in the registry record.

The trial is labeled triple-masked. The record does not identify which groups of people were masked, how masking was maintained, or whether masking was assessed. Those details matter for understanding possible influences on treatment delivery, participant behavior, outcome measurement, and analysis; they cannot be inferred from the masking label alone.

The recorded study dates are 2015-05 for start and 2018-10 for primary completion, and the status is completed. The primary outcome was normative isokinetic knee-extension strength at 26 weeks post-operation. The record also lists a range of secondary strength outcomes, including isokinetic and isometric measures at different times. There are 44 outcome measures and 44 analyses listed overall; 43 secondary outcomes are posted.

The registry record does not report the planned sample-size justification, treatment regimen, detailed eligibility criteria, allocation procedure, or a complete statistical analysis plan. In particular, it does not establish from the information recorded how the trial's enrollment target was selected or which analyses were prespecified. These omissions limit reconstruction of the design and analysis decisions.

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: A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

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: Of the 20 subjects who began the study, 19 were included in the baseline analysis. One subject who withdrew from the study was not included in the analysis

6. Primary Endpoint

The registry lists the primary outcome as Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op, measured over at 26 wks post-op.

The primary endpoint is normative isokinetic knee-extension strength, measured in newton meters (Nm) at 26 weeks post-operation. The registry record says measurements were obtained using a System 3 dynamometer. Isokinetic testing was performed at 60º/sec through a range of 0º to 90º of knee flexion, and the highest force from a series of 5 repetitions was used for each measurement.

The value was normalized by dividing the injured-limb measurement by the value from the contralateral, uninjured leg before surgery. This creates a relative measure intended to put strength in the injured limb in the context of the participant's own uninjured side. It is not the same as an absolute strength measurement, and it should not be interpreted as a direct measure of muscle mass or of overall clinical recovery.

Strength is used as a functional outcome because muscle force is relevant to the muscle impairment described in the trial rationale. Isokinetic testing measures force under controlled movement conditions, which can support consistent assessment across participants. As a general statistical point, however, a measured endpoint captures only the construct and time point it was designed to assess. It does not by itself establish effects on symptoms, participation, later injury, or other outcomes not measured by this primary endpoint.

The record reports means with 90% confidence intervals for each arm. The Somatropin mean was 0.881, with a 90% confidence interval from 0.701 to 1.061; the Placebo mean was 0.681, with a 90% confidence interval from 0.532 to 0.83. The reported primary endpoint analysis included 10 participants in the Somatropin arm and 9 in the Placebo arm.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the normalized strength measure represent?

The endpoint is based on an injured-limb strength measurement relative to the participant's contralateral, uninjured limb before surgery. Normalization can make a result easier to interpret in relation to the participant's own reference value, rather than treating the raw dynamometer reading as the only quantity of interest. The resulting measure is a ratio-like normalized value, not a raw Nm value despite the endpoint title's unit. The record reports the measurement method and normalization rule, but does not explain why this particular normalization was selected or how it was handled in the statistical model.

As a general point, a normalized measure depends both on its numerator and its reference value. It may be useful for comparing relative strength, but it is not interchangeable with absolute injured-limb strength. Differences in the reference measure can affect the normalized result. The registry record does not report a separate analysis of the normalization components for this primary endpoint.

What do the arm means and confidence intervals tell us?

The posted arm means describe the average normalized outcome within each analyzed group. The Somatropin arm has a mean of 0.881 and a 90% confidence interval of 0.701 to 1.061. The Placebo arm has a mean of 0.681 and a 90% confidence interval of 0.532 to 0.83. These figures describe group-level estimates and their uncertainty; they do not reveal the distribution of individual outcomes or the proportion of participants with a particular response.

In general, a confidence interval is constructed by a statistical procedure that would, under its assumptions, cover the target quantity at the stated rate over repeated applications. It is not a guarantee about the particular interval, and it does not account automatically for all design limitations, missing data, or selective reporting. The registry record labels these intervals as 90% confidence intervals, but does not describe how the arm-level intervals were calculated.

How should the mixed models result be read?

The registry record names Mixed Models Analysis as the method for the comparison and reports p = 0.050. Mixed models are a broad class of methods that can represent correlated or repeated observations and account for modeled sources of variation. In general, their usefulness depends on the model structure, outcome distribution, covariance assumptions, included terms, and handling of incomplete observations. The registry record does not report those specifications for this analysis. It is therefore not possible to reconstruct the precise model or verify which observations and covariates contributed to the test.

A p-value summarizes how unusual the data, or data more extreme, would be under a specified null model and its assumptions. It does not measure the size of an effect. Nor does it indicate the probability that a treatment hypothesis is true. The reported value should be considered alongside the arm estimates, their uncertainty, the small analyzed groups, the number of outcomes, and the missing details of the model and analysis plan.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when the variability in data is greater than a model's assumptions allow. If a model understates variability, standard errors can be too small and confidence intervals or tests can appear more precise than warranted. The primary endpoint is a continuous strength measure, and the registry record does not report a dispersion estimate or a diagnostic for over-dispersion. This is not evidence that over-dispersion occurred; it is a reminder that model adequacy depends on information not given in the record.

What does the planning illustration mean?

The record describes sample-size planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the illustrated effect to detect is a stated fraction of the observed effect. These are planning scenarios, not observed trial outcomes and not a retrospective measure of the probability that the trial detected an effect. The numerical illustration results and the fractions used are not reported in the registry record.

As a general explanation, a planning calculation asks what sample size might be needed under chosen assumptions about the target effect, variability, significance level, allocation, and desired power. Such a calculation is only as informative as its assumptions. When the target effect is derived from an observed effect, the observed estimate may be imprecise, especially in a small study. A planning illustration cannot establish that the original design was adequately powered, because the registry record does not report the trial's own sample-size justification or its assumed target effect.

10. Analyses Reported by the Sponsor

The registry record reports a sponsor-level comparison using Mixed Models Analysis, with p = 0.050. It does not report a model-based between-arm estimate or confidence interval for that comparison. The arm-level means and 90% confidence intervals are useful descriptive summaries, but they are not substitutes for the model-based contrast, particularly when the stated analysis method is a mixed model.

No separate unadjusted recalculation of the treatment contrast is reported in the registry record. Consequently, there is no recalculated comparison to set alongside the sponsor's test or to use to assess numerical agreement. The posted result supports describing the mixed-model p-value and the separate arm means, but not claiming that an independent calculation confirms a particular effect estimate.

The record does not document a discrepancy between a sponsor analysis and a recalculation. The mixed-model result should be read according to what is actually reported: the method label and the p-value. Because the model specification, treatment-effect estimate, and its uncertainty are not reported, the result cannot be fully audited or interpreted as a precise estimate of the magnitude of the treatment contrast. A p-value alone does not supply those missing quantities.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 44 outcome measures and 44 analyses, and 43 secondary outcomes are posted. The primary endpoint is normative isokinetic knee-extension strength at 26 weeks post-operation. The record does not say how the other endpoints and analyses were organized into primary, secondary, or exploratory testing families, beyond identifying the primary outcome and listing secondary outcomes.

Multiplicity is the statistical issue that arises when many hypotheses are tested. In general, if many tests are conducted, the probability of at least one result crossing a conventional threshold can be higher than for a single prespecified test. Statistical plans can address this through a hierarchy, adjusted thresholds, or other methods, but those approaches answer different questions and can affect interpretation. The registry record does not report whether any such method was used, whether analyses were prespecified, or how the reported primary p-value relates to testing of the other outcomes.

Missing-data handling is also not reported for the primary analysis. Enrollment was 20, while 19 participants were analyzed for bilateral isokinetic knee strength. The record does not state why these counts differ, whether all randomized participants were included in the analysis, how incomplete measurements were treated, or whether any imputation method was used. It also does not report a sensitivity analysis for missing outcomes.

The analyzed population is described as participants analyzed for bilateral strength, but the registry record does not give a detailed analysis-population definition. It does not state whether analysis followed an intention-to-treat principle, a per-protocol definition, or another approach. These distinctions can matter because the population included in an analysis and the treatment assignment used for that analysis affect the interpretation of a randomized comparison.

These absences do not show that multiplicity, missing data, or analysis-population issues were handled inadequately. They mean the handling cannot be established from the registry record. The p-value and arm summaries should therefore be interpreted with those uncertainties in mind, rather than assuming an adjustment, complete follow-up, or a particular analysis population.

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 record reports zero serious adverse events among 10 participants at risk in the Somatropin arm and zero among 9 participants at risk in the Placebo arm. It also reports zero deaths in each arm. These are the recorded counts for the participants at risk; they do not establish that no serious events could occur or that the treatments have equivalent safety.

For other, non-serious adverse events, the record reports 5 affected participants among 10 at risk in the Somatropin arm and 5 among 9 at risk in the Placebo arm. These are participant counts, not a comparison adjusted for follow-up time, severity, or other factors. The registry record does not provide event descriptions for these non-serious events in the information, so their clinical nature and distribution cannot be assessed.

In general, safety counts from small groups provide limited information about uncommon outcomes. A count of zero means no event was recorded in the observed group during the reported period; it does not prove the underlying risk is zero. The record does not report a detailed safety-analysis method, exposure duration, or further event-level context. These figures should be treated as descriptive registry results, not as a comprehensive safety assessment.

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

The posted results show that the Somatropin arm had a higher mean normalized isokinetic knee-extension strength than the Placebo arm at 26 weeks post-operation: 0.881 compared with 0.681. The registry record reports a mixed models comparison with p = 0.050. The 90% confidence intervals around the arm means indicate uncertainty in those estimates, and the record does not give a model-based contrast estimate or interval to quantify the between-arm difference directly.

Statistically, the reported p-value is close to a commonly used threshold, but it is not a measure of effect size, clinical importance, or the probability that the treatment hypothesis is correct. The result's interpretation is also affected by the small analyzed groups, the 44 listed outcome measures and analyses, and the lack of detail about multiplicity handling and model specification. The record does not report the trial's own sample-size justification, so it cannot establish the precision the investigators intended to achieve.

The result does not demonstrate a change from baseline, because the posted primary outcome is a postoperative normalized measurement and no primary baseline-to-follow-up contrast is reported. It does not show whether any difference was meaningful to participants, or whether it affected activity, return to play, reinjury, osteoarthritis, or quality of life. Those outcomes are not established by a strength measurement alone.

The finding also does not establish that the treatments differ on every strength outcome. The registry lists multiple secondary measures, but their results and analysis details are not described in this primary result. Nor do the serious adverse event counts establish comparative safety: zero serious events were reported in either arm, in groups of 10 and 9 at risk.

The most defensible reading is narrow: the registry reports arm-level strength means and a mixed-model p-value at the stated time point, with important uncertainty about the estimated contrast, model details, missing data, and multiplicity. The result is a statistical observation from a small trial, not a standalone conclusion about broader recovery or treatment effects.

14. Why This Trial Matters Statistically

This trial matters statistically because it connects a biological rationale with a measurable functional endpoint. The registry describes an interest in muscle atrophy and strength loss after ACL tears, then evaluates normalized isokinetic knee-extension strength at a defined postoperative time. Careful distinction between the proposed mechanism and the measured outcome is essential: the endpoint directly concerns strength, not muscle size or long-term clinical consequences.

The design is randomized and parallel-group, which provides a framework for comparing assigned interventions. At the same time, the primary analysis includes 19 participants, with 10 in the Somatropin arm and 9 in the Placebo arm. The trial therefore illustrates why a point estimate and p-value must be considered alongside uncertainty and the amount of information available. A reported p-value near a conventional cutoff cannot stand in for the magnitude and precision of the treatment contrast.

The record also illustrates the value of transparent reporting. The arm means and confidence intervals are available, as is the mixed-model p-value, but the model details and treatment-effect interval are not. The registry lists numerous outcomes and analyses without reporting whether multiplicity was addressed. Those omissions make it harder to assess robustness and place the primary test within the full analysis context.

Finally, safety counts and efficacy outcomes answer different questions. The zero serious adverse events reported in either arm are descriptive observations in small groups, not proof of no risk. Taken together, the record offers a focused example of how trial design, measurement choices, uncertainty, multiplicity, analysis reporting, and small samples shape interpretation. These considerations are relevant even when the statistical result appears close to a familiar threshold.

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 primary endpoint analysis includes 19 participants, although enrollment was 20. The registry record does not explain the difference or state how any missing measurements were handled. Without that information, it is not possible to assess whether the analyzed participants represent all randomized participants or whether missingness could have influenced the result.

The reported comparison is identified as a mixed models analysis, but the model specification is not reported. The record does not give the treatment-effect estimate or confidence interval from that model, nor does it describe the covariance structure, included terms, or assumptions. The arm means and their 90% confidence intervals do not fill this gap, because they are not the model-based contrast.

The registry record lists 44 outcome measures and 44 analyses, including 43 secondary outcomes. It does not state how multiplicity was handled, which analyses were prespecified, or whether a hierarchy distinguished confirmatory from exploratory results. This makes the reported p-value harder to interpret in the full testing context.

Other design details are also absent from the registry record, including the dose and schedule of somatropin, the allocation method, the specific groups included in triple masking, and the trial's own sample-size justification. The record does not report a detailed definition of the analysis population or sensitivity analyses for missing data. These details are relevant to judging reproducibility and potential sources of bias.

The endpoint is a normalized strength measurement at 26 weeks post-operation. It does not directly assess muscle size, broader function, return to activity, reinjury, osteoarthritis, or quality of life. The reported safety results are similarly limited: event descriptions and fuller follow-up context are not reported in the registry record. These limitations do not establish that bias or harm occurred; they define what can and cannot be concluded from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears — NCT02420353.
• Registry record last updated 2020-01-06; status last verified 2019-12.
• Results first posted 2020-01-06.
• 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

The registry record describes a completed phase 2 randomized, triple-masked, parallel-group trial sponsored by the University of Michigan. It enrolled 20 participants with ACL rupture and compared somatropin with placebo. The primary outcome was normalized isokinetic knee-extension strength at 26 weeks post-operation.

The primary endpoint analysis included 19 participants: 10 in the Somatropin arm and 9 in the Placebo arm. The reported means were 0.881 and 0.681, with respective 90% confidence intervals of 0.701 to 1.061 and 0.532 to 0.83. The registry reports a mixed models analysis with p = 0.050, but does not report the model-based treatment-effect estimate or its confidence interval.

The record lists 44 outcome measures and analyses, with 43 secondary outcomes posted. Details about multiplicity, missing-data handling, analysis populations, and the model specification are not reported in the registry record. Serious adverse events and deaths were reported as zero in both arms; other adverse events affected 5 participants in each arm.