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 Effect of a Ghrelin Receptor Agonist on Muscle and Bone (NCT04021706), a randomized phase 1 study. The primary outcome is Total Body Muscle Mass.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04021706 |
| Phase | Phase 1 |
| Condition | Sarcopenia, Osteopenia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 32 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Tufts University |
| Results posted | Yes |
2. Clinical Question
Population
The registry summary describes adults with low muscle mass and low bone mass; the listed conditions are sarcopenia and osteopenia. It gives an enrollment of 32. The detailed eligibility criteria, including how low muscle and bone mass were defined, are not reported in the registry record. The summary frames the clinical concern as vulnerability to falls, fractures, and other injuries. These are the context for the trial question, not outcomes reported by this record.
Intervention
The intervention was anamorelin hydrochloride. The arm description specifies one 100 mg tablet daily, taken one hour before breakfast. The primary question concerns short-term indicators of muscle and bone health, with total body muscle mass designated as the primary outcome and assessed at baseline and 12 months. The record does not provide outcome values showing how this measure changed during treatment.
Comparator
The comparator was placebo, described as one identical-appearing tablet daily, taken one hour before breakfast. The arm description identifies microcrystalline cellulose as the tablet content. The registry reports a randomized, parallel design, but does not describe the randomization sequence or allocation procedures. The masking is recorded as triple; which specific roles were masked is not reported in the registry record.
Primary question
The primary question is whether assignment to anamorelin or placebo is associated with a difference in total body muscle mass, measured in kg units on a scale by D3-creatine dilution at baseline and 12 months. The endpoint is recorded as a mean with standard deviation. No group means, changes, treatment-effect estimate, confidence interval, or test result for this endpoint are reported in the registry record. The available entry therefore defines the comparison but does not establish its result.
3. Trial Design
This was a randomized, triple-masked, parallel-group phase 1 trial sponsored by Tufts University. The registry lists the study as completed, with an enrollment of 32. Its recorded start date is 2019-12-05, and its primary completion date is 2023-01-26. These dates describe the registered study timeline; they do not supply information about when individual participants entered or completed follow-up.
Participants were assigned to anamorelin hydrochloride or placebo. The active arm is described as taking one 100 mg tablet daily, one hour before breakfast. The comparator arm is described as taking one identical-appearing tablet daily at the same time, with microcrystalline cellulose identified in the arm description. The registry gives the masking level as triple but does not identify which people or study roles were masked. Details of the randomization procedure, allocation concealment, treatment adherence, and permitted co-interventions are not reported in the registry record.
The clinical context is adults with low muscle mass who also usually have low bone mass, as described in the registry summary. Sarcopenia and osteopenia are the listed conditions. The exact inclusion and exclusion criteria, recruitment setting, and participant characteristics are not reported in the registry record, so the enrolled population cannot be characterized in greater detail from this entry.
The stated aim was to assess short-term indicators of muscle and bone health and to inform the design of a larger randomized trial intended to establish efficacy. The primary outcome is total body muscle mass, assessed by D3-creatine dilution at baseline and 12 months. The record lists secondary outcomes including serum P1NP, fasting plasma glucose, AST, ALT, participants with symptoms and any adverse events, and appendicular lean mass. It records 13 outcome measures overall, but the available information does not give results for these outcomes.
The registry identifies no statistical analyses. The detailed protocol, analysis plan, sample-size justification, interim-analysis plan, and analysis populations are not reported in the registry record. The study designation and stated aim should therefore be read alongside the absence of posted endpoint estimates: design information alone cannot establish the size, precision, or direction of a treatment effect.
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 | Anamorelin | Microcrystaline Cellulose |
|---|---|---|
| STARTED | 17 | 15 |
| COMPLETED | 13 | 13 |
| NOT COMPLETED | 4 | 2 |
Reasons for not completing this period:
| Reason | Anamorelin | Microcrystaline Cellulose |
|---|---|---|
| Adverse Event | 2 | 0 |
| Withdrawal by Subject | 1 | 2 |
| Physician Decision | 1 | 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.
Population: Baseline characteristics are based on completers, 13 in each arm.
| Characteristic | Unit | Anamorelin | Microcrystaline Cellulose | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 13 | 26 | |
| Age, Continuous | years | 73.2 (SD 5.8) | 75.7 (SD 6.4) | 74.5 (SD 6.0) |
| Sex: Female, Male: Female | Participants | 5 | 4 | 9 |
| Sex: Female, Male: Male | Participants | 8 | 9 | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 11 | 11 | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 13 | 13 | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Total Body Muscle Mass, measured over baseline and 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | kg units on a scale |
| Endpoint classification | Continuous Endpoint |
Total body muscle mass is the primary endpoint. It is a continuous measure, recorded in kg units on a scale, and the registry specifies reporting as a mean with standard deviation. The measurement method is D3-creatine dilution, with assessments at baseline and 12 months. The endpoint focuses on muscle mass rather than a clinical event such as a fall or fracture.
In general, a measure of muscle mass can be used to assess whether body composition changes during a study. A baseline measure provides a starting point for describing participants, while a later measure permits assessment of change over time or comparison between assigned groups. The value of such an endpoint depends on how reliably it is measured and on how the analysis handles baseline values, missing measurements, and variation among participants. Details of those procedures are not reported in the registry record.
The registry summary links low muscle mass with low bone mass and injury vulnerability, and describes the trial as examining short-term indicators of muscle and bone health. That context explains the choice of a muscle-mass outcome, but the endpoint itself does not directly measure falls, fractures, or injuries. Nor does the measurement, by itself, establish whether any change matters to participants. The record does not report a threshold for a meaningful change or a clinical interpretation for a particular difference.
No mean values, standard deviations, changes from baseline, or between-group estimates for total body muscle mass are reported in the registry record. Consequently, the endpoint definition is available, but its observed result and precision cannot be assessed from the registry entry.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a randomized comparison of anamorelin hydrochloride with placebo and identifies total body muscle mass as the primary endpoint. However, it does not report numerical primary-outcome results or any statistical analyses. There is therefore no posted group mean, change from baseline, treatment-effect estimate, confidence interval, or p-value from which to assess the direction, size, or precision of the primary comparison. The record supports a description of the intended question and measurement, not a conclusion about the observed effect.
The primary measure is scheduled at baseline and 12 months, and is defined as a mean with standard deviation using D3-creatine dilution. A mean describes the average measurement in a group; a standard deviation describes how dispersed individual measurements are around that average. Neither statistic is reported for the primary outcome. Without them, the extent of variation and the separation between groups cannot be examined. Without a treatment-effect estimate and its uncertainty, it is also not possible to judge whether the data are compatible with effects of different sizes.
The registry lists 13 outcome measures and names several secondary outcomes, including P1NP, fasting plasma glucose, AST, ALT, participants with symptoms and any adverse events, and appendicular lean mass. It does not report results for these measures. The primary outcome is also flagged as having several categories or time points and not being reduced to one comparison. The particular categories or comparisons are not described in the available record, so a single primary contrast cannot be reconstructed.
The safety entry reports affected-participant counts for serious and other adverse events by arm, along with zero deaths in each arm. These counts describe what the record reports, but they do not include enough detail to establish event timing, severity beyond the serious/other categorization, relatedness to treatment, or how events were collected. The listed serious-event terms have percentages but are not assigned to a treatment arm in the record. These entries should not be treated as proof that treatment caused or prevented an event.
Randomization is a design feature intended, in general, to reduce systematic differences between assigned groups. It does not guarantee that the groups were alike in every characteristic, especially in a study of this size, and baseline characteristics are not reported. Triple masking may reduce some opportunities for expectations to influence care or assessment, but the masked roles and the success of masking are not reported in the registry record.
The record's stated purpose was to inform a larger randomized trial designed to establish efficacy. That purpose is consistent with treating the study as an early investigation of short-term indicators, rather than reading it as a definitive efficacy assessment. The phase designation and completion status do not substitute for outcome estimates. Since the registry contains no analyses, the magnitude and precision of any treatment effect, as well as the statistical compatibility of the results with a null or clinically important effect, are not reported in the registry record.
9. Statistical Methods Explained
The registry identifies the study as randomized, triple-masked, and parallel. In general, random assignment is used to make treatment groups comparable in expectation with respect to measured and unmeasured factors. It does not ensure exact balance in a particular trial. A parallel design means participants are assigned to a group whose treatment is compared with the other group; the registry does not describe any crossover. The specific sequence generation, allocation concealment, and procedures used to maintain masking are not reported in the registry record. The record also does not identify who was masked, so the meaning of triple masking cannot be made more specific.
The primary measure is continuous: total body muscle mass, expressed in kg units on a scale. The registry specifies the mean and standard deviation as the summary statistics. In general, the mean describes the group average, while the standard deviation describes the spread of observations around that average. These quantities answer different questions. A small standard deviation can indicate relatively clustered measurements, while a larger one indicates more variability; neither alone measures the precision of a treatment comparison. Precision also depends on the amount of information in the analysis and the method used to estimate uncertainty.
A treatment comparison may be expressed as a difference in means or as a comparison of changes over time. Such estimates are usually interpreted with a confidence interval, which gives a range of values compatible with the data under the chosen statistical model and confidence procedure. A narrower interval indicates greater precision than a wider interval, all else equal. A confidence interval does not give the probability that the true effect lies within that particular interval. No treatment-effect estimate or confidence interval for the primary outcome is reported in the registry record, and the exact primary comparison is not specified.
The primary outcome is scheduled for baseline and 12 months. In general, baseline measurements can be used to describe the initial groups and may be incorporated in an analysis to improve precision. Repeated measurements can also be analyzed by comparing follow-up values, changes from baseline, or trajectories over time. These approaches answer related but not identical questions and rely on different assumptions. The registry does not state which approach was planned or used, whether adjustment for baseline was made, or how repeated measurements were handled.
A p-value, when reported, quantifies how incompatible the observed data are with a specified null model, conditional on the assumptions of the analysis. It is not a measure of effect size, clinical importance, or the probability that a treatment works. A p-value also cannot replace an estimate and its confidence interval. No p-values or tests for the primary or secondary outcomes are reported in the registry record. The record reports zero analyses, so inferential procedures cannot be attributed to the trial from this entry.
The registry's planning description refers to a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation for sample-size illustrations. It also says the illustrative effect to detect is a stated fraction of the observed effect. Such illustrations are planning exercises based on an effect estimate; they are not observed power and do not demonstrate what the trial was capable of detecting after results were observed. The actual illustration values and the observed effect on which they depend are not reported in the registry record. The trial's own sample-size justification is not reported in the registry record.
The description also distinguishes planning quantities for time-to-event outcomes from those for other outcomes. The primary outcome is continuous, so the general interpretation of a continuous-outcome planning calculation is participants per arm for a chosen power and assumed effect. A planning estimate depends on assumptions about variability, effect size, allocation, and the testing procedure. If those assumptions differ from the eventual data, the planning estimate may not describe the realized precision. No specific planning estimate is reported in the registry record.
Over-dispersion is a general concern when the observed variability is greater than a model assumes. For a continuous endpoint, greater variability can make estimates less precise than anticipated under a lower-variability assumption. For count or event data, over-dispersion can make standard errors too small if a model assumes less variability than the data contain. The registry does not report a model for the primary outcome or indicate whether over-dispersion was assessed; this is a general statistical consideration, not a description of an analysis performed in this trial.
Missing measurements can affect interpretation if participants with observed outcomes differ systematically from those without them. In general, an analysis may use complete observations, impute missing values, or apply a model that uses available repeated measures, among other approaches. Each method has assumptions, and sensitivity analyses can assess how conclusions change under alternative assumptions. The registry record does not report missing-outcome counts, reasons for missingness, an imputation method, or a sensitivity analysis. It also does not identify the analysis population, such as whether participants were analyzed according to randomized assignment or treatment received.
Finally, multiple outcomes or comparisons raise multiplicity concerns. In general, testing many hypotheses can increase the chance of at least one apparently unusual result when all null hypotheses are true. Approaches such as prespecifying a primary comparison or adjusting for multiple tests can address different aspects of this issue, but the appropriate choice depends on the planned questions. The registry lists multiple outcome measures and notes that the primary outcome has several categories or time points and is not reduced to one comparison. Whether a multiplicity strategy was prespecified or applied is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 13 outcome measures, including the primary total body muscle-mass measure and secondary measures such as P1NP, fasting plasma glucose, AST, ALT, symptoms and any adverse events, and appendicular lean mass. Multiple outcomes can be useful when a study examines several aspects of health, but multiple testing makes it important to define which comparisons are primary and how other analyses will be interpreted. In general, testing many hypotheses without an appropriate plan can make chance findings more likely. The registry does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for interpreting secondary outcomes.
The primary outcome entry is flagged as having several categories or time points and not being reduced to one comparison. The record specifies baseline and 12 months, but does not explain the other categories or identify a single contrast. The analysis plan and the approach to multiple time points are not reported in the registry record. No analyses are reported, so the registry does not establish which comparisons were conducted.
Missing-data details are also absent. The registry does not report the number of participants with primary measurements at each assessment, reasons for missing measurements, or methods for handling missing data. In general, missingness can affect a comparison when the probability of having an observed measurement is related to participant characteristics or outcomes. The assumptions and sensitivity analyses used to address this possibility are not reported in the registry record.
The analysis population is not reported in the registry record. It is therefore not possible to tell whether analyses followed randomized assignment, included only participants who completed treatment, or used another definition. The registry also does not report a protocol-specific sample-size justification or interim-analysis plan. These omissions limit evaluation of how the analyses were planned and whether the posted results, if available, would correspond to prespecified methods.
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 |
|---|---|---|---|
| Anamorelin | 1 | 17 | 5.9% |
| Microcrystaline Cellulose | 1 | 15 | 6.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Anamorelin | 0 of 17 |
| Microcrystaline Cellulose | 0 of 15 |
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 |
|---|---|
| Anamorelin | 3 of 17 |
| Microcrystaline Cellulose | 1 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Anamorelin | Microcrystaline Cellulose |
|---|---|---|---|
| hematuria | Renal and urinary disorders | 1 of 17 | 0 of 15 |
| heart valve regurgitation | Cardiac disorders | 0 of 17 | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Anamorelin | Microcrystaline Cellulose |
|---|---|---|---|
| GI bloating | Gastrointestinal disorders | 2 of 17 | 0 of 15 |
| leaky heart valve | Cardiac disorders | 0 of 17 | 1 of 15 |
| high blood sugar | Metabolism and nutrition disorders | 1 of 17 | 0 of 15 |
Serious events with the highest arm-level rate: heart valve regurgitation (6.7%), hematuria (5.9%).
The registry reports serious adverse events and other adverse events separately for the two arms. In the anamorelin group, 1 of 17 participants at risk was reported as affected by a serious adverse event, and 3 of 17 were affected by other adverse events. In the microcrystalline cellulose group, 1 of 15 participants at risk was reported as affected by a serious adverse event, and 1 of 15 was affected by other adverse events. The record reports 0 deaths in each group.
These are counts of participants reported as affected in the listed categories. The entry does not provide event-level descriptions for those counts, timing, duration, severity criteria, or an assessment of whether events were related to assigned treatment. The record lists heart valve regurgitation at 6.7% and hematuria at 5.9% among the top serious terms, but does not assign those terms to an arm in the available information. They should not be attributed to a particular group on this basis.
In general, adverse-event counts describe what was recorded under a study's collection and classification procedures. They do not by themselves establish causation or comparative risk. The registry record does not provide details of event ascertainment or statistical comparisons, so the entries support a limited description of reported events rather than a causal safety conclusion.
12. What the Result Does, and Does Not, Mean
The record establishes the trial's registered question and some aspects of its design. It describes a randomized comparison of daily anamorelin hydrochloride with a matching placebo in adults described as having low muscle and bone mass. Total body muscle mass, measured by D3-creatine dilution at baseline and 12 months, is identified as the primary endpoint. The record also gives limited adverse-event counts by arm.
It does not report the primary endpoint values, a between-group estimate, confidence interval, or p-value. It also does not report results for the listed secondary outcomes. Without these results, the direction and size of any observed difference cannot be evaluated, and the precision of an estimate cannot be judged. The registry therefore does not establish whether the intervention changed total body muscle mass relative to placebo.
The endpoint is a measure of muscle mass, not a direct measure of falls, fractures, injuries, or other outcomes described in the clinical rationale. Even a measured difference in muscle mass would not, by itself, demonstrate a change in those outcomes. The record does not state a threshold for a meaningful change or provide a clinical interpretation for the endpoint.
The listed safety counts also have limits. They do not establish that treatment caused or prevented events, and the serious-event terms are not linked to an arm in the record. Zero reported deaths in each arm is a description of the registry entry, not a general guarantee about safety. Details needed to interpret event collection and relatedness are not reported in the registry record.
The registry says the trial was intended to inform a larger randomized trial designed to establish efficacy. That stated purpose is important context: the entry describes an early investigation of short-term indicators, but supplies no outcome analyses that would support an efficacy conclusion. A completed status means the registry lists the study as completed; it does not fill the gap left by absent results. The conclusions that can be drawn are therefore about the registered design and the information recorded, not about whether anamorelin was effective or ineffective.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the distinction between a registered research question and an interpretable treatment-effect result. The record specifies randomization, masking, the parallel-group structure, a continuous primary endpoint, its measurement method, and the planned assessment times. Those details help identify what investigators intended to compare. They do not provide the estimates needed to understand what the comparison found.
For a continuous endpoint, interpretation generally depends on the observed group summaries, an estimate of the between-group effect, and a measure of uncertainty. A mean and standard deviation describe the data, while a confidence interval for the treatment contrast helps communicate precision. Here, the endpoint is defined as a mean with standard deviation, but no outcome values or treatment-effect estimate are reported in the registry record. That absence prevents assessment of both magnitude and uncertainty.
The record also brings attention to the relationship between planning and evidence. It describes sample-size illustrations based on the observed effect and specified assumptions, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations can help plan future research, but they are not observed power and cannot substitute for an estimate with uncertainty. The observed effect and numerical planning illustrations are not reported in the registry record.
Multiplicity and missing-data methods also matter when interpreting a trial with several outcome measures and repeated assessment times. The registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison, while the analysis plan and missing-data procedures are not reported. These details would be important for evaluating how a primary result was selected and how incomplete measurements were handled.
Because the stated aim was to inform a larger trial, the record is relevant as an example of an early study whose registered design is clearer than its posted statistical results. Transparent reporting of outcome estimates, uncertainty, analysis populations, and planned methods would be needed to judge how these data should inform subsequent research.
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 interpreting this trial from the registry record is the absence of outcome results and statistical analyses. The primary endpoint is defined, but group means, standard deviations, changes, treatment-effect estimates, confidence intervals, and tests are not reported. Results for the listed secondary outcomes are also not reported. This prevents assessment of the observed direction, magnitude, and precision of the findings.
The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison, but it does not identify the specific categories or state which contrast was primary in analysis. The timing is given as baseline and 12 months, yet the analysis approach for repeated measurements is not reported. The trial's protocol and analysis plan are not reported in the registry record, including the sample-size justification, statistical model, and any interim-analysis plan.
Important population and implementation details are unavailable. The summary describes adults with low muscle and bone mass and lists sarcopenia and osteopenia, but detailed eligibility criteria and participant characteristics are not reported. The record also does not report adherence, withdrawals, treatment exposure, or reasons for missing outcome measurements. The analysis population and methods for missing data are not reported in the registry record.
The masking designation is recorded as triple, but the roles masked and procedures for maintaining masking are not specified. Randomization procedures are also not described. For safety, the record gives affected-participant counts but not event timing, relatedness, ascertainment procedures, or arm attribution for the listed serious-event terms. These limits restrict interpretation to the information recorded and do not support a complete assessment of efficacy or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of a Ghrelin Receptor Agonist on Muscle and Bone — NCT04021706.
- Registry record last updated 2024-03-27; status last verified 2024-02.
- Results first posted 2024-03-27.
- 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
NCT04021706, titled “Effect of a Ghrelin Receptor Agonist on Muscle and Bone,” is listed as a completed phase 1 randomized, triple-masked, parallel trial sponsored by Tufts University. The registry records enrollment of 32, a start date of 2019-12-05, and a primary completion date of 2023-01-26. The listed conditions are sarcopenia and osteopenia.
The intervention was anamorelin hydrochloride, described as one 100 mg tablet daily taken one hour before breakfast. The comparator was an identical-appearing microcrystalline cellulose tablet taken on the same schedule. Total body muscle mass, measured by D3-creatine dilution at baseline and 12 months, is the primary outcome. The registry also lists secondary outcomes covering bone and metabolic markers, liver enzymes, adverse events, and appendicular lean mass.
The entry reports limited adverse-event counts but no primary or secondary outcome analyses. The magnitude and precision of any treatment effect, analysis methods, missing-data handling, and analysis populations are not reported in the registry record.