Effect of Caloric Restriction and Protein Intake on Metabolism and Anabolic Sensitivity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Caloric Restriction and Protein Intake on Metabolism and Anabolic Sensitivity (NCT02945410), a randomized na study. The primary outcome is Change in Resting Metabolic Rate.

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, single-masked, crossover trial. Its status is completed, and the listed enrollment is 20. The start is recorded as 2016-09 and primary completion as 2019-02. The condition labels include weight loss and starvation. The sponsor is University of Nebraska Lincoln. The registry lists the phase as NA.

Three condition descriptions are posted. In the high-protein caloric-restriction condition, participants were to receive 30 kcal/kg FFM/day and 1.7 g protein/kg BW/day. In the normal-protein caloric-restriction condition, the calorie restriction was also 30 kcal/kg FFM/day, with 0.8 g protein/kg BW/day. In the energy-balance condition, participants were to be in energy balance and consume 1.7 g protein/kg BW/day. These descriptions distinguish the intended energy and protein conditions; they do not establish how adherence was assessed or achieved.

A crossover design generally compares conditions within participants, which can reduce the influence of stable differences between people. That general advantage depends on the actual sequence, timing, and analysis. The registry record does not report the treatment sequence, duration of each period, washout procedures, or whether order effects were assessed. It also does not identify who was masked. Randomization is recorded, but the randomization procedure and allocation details are not reported in the registry record.

The primary outcome is change in resting metabolic rate from baseline to day 6. Four secondary outcomes are listed: change in body weight, body fat percentage, aerobic fitness (VO2peak), and perceived hunger. Eight outcome measures are listed overall. The record lists no analysis entries, and comparative inferential results are not included in the registry record. The reported outcome summaries therefore support a descriptive reading, not a reconstruction of the trial’s full statistical analysis.

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.

Before assignment: Participants Excluded prior to assignment: n = 4 did not meet inclusion criteria on preliminary questionnaires (n = 1 did not met the age requirements (reported a false age) n = 1 reported hyperthyroidism n = 2 reported insufficient levels of physical activity) n = 1 declined to participate in the study after enrolling

Intervention 1 (5 Days)

Reasons for not completing this period:

Washout 1 (14 Days)

Reasons for not completing this period:

Intervention 2 (5 Days)

Washout 2 (14 Days)

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Change in Resting Metabolic Rate, measured over Baseline and day 6.

Resting metabolic rate is the energy expenditure measured while a person is at rest. The registered endpoint is its change, in kcal, from baseline to day 6. It is a continuous measure, and the posted summary is a mean change for each condition, with standard error as the measure of dispersion. Each reported mean is negative: -63.4 for caloric restriction and high protein, -77.6 for caloric restriction and normal protein, and -47.4 for energy balance. The corresponding standard errors are 58.2, 100.1, and 41.7.

As a general statistical concept, resting metabolic rate can be used to describe one component of energy expenditure and to examine how it changes over an intervention period. A mean summarizes the average change in a group, while the standard error conveys the estimated precision of that mean. These summaries do not show the range of individual responses, and the record does not provide confidence intervals for these estimates.

The endpoint is related to the trial’s interest in metabolism, but it is not interchangeable with hormone concentrations or anabolic sensitivity of bone and skeletal muscle. Those broader topics appear in the official title and study purpose; the reported primary measure is specifically resting metabolic rate. The registry does not report the measurement protocol or any further details about how the outcome was assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The results are continuous-outcome summaries: each condition has a mean change in resting metabolic rate and a standard error. The record identifies the measure as change from baseline to day 6, with units of kcal change. A mean is the arithmetic center of the observed outcome values. It gives a compact description of the group’s average, but it does not show whether participants had similar changes or varied widely. The standard error describes the estimated precision of the mean; it is not the standard deviation of individual outcomes.

What does a standard error tell the reader?

As a general statistical explanation, a standard error reflects how much an estimate would vary across repeated samples under a statistical model. A smaller standard error indicates a more precisely estimated mean, all else equal. It does not, on its own, quantify uncertainty in a contrast between two conditions. That requires an estimate of the contrast and its uncertainty, with the analysis accounting for the design and any relevant correlation.

The reported standard errors are 58.2 for caloric restriction and high protein, 100.1 for caloric restriction and normal protein, and 41.7 for energy balance. The record does not provide confidence intervals. A confidence interval is a range calculated by a specified method to express uncertainty around an estimate; its interpretation depends on the method and assumptions used. No interval should be inferred from these means and standard errors without making additional calculations and assumptions.

Why does the crossover label matter?

In general, a crossover trial assigns participants to experience more than one study condition, so measurements under different conditions from the same person are often statistically related. An analysis that treats all condition observations as independent may fail to represent that relationship. A paired comparison or a suitable repeated-measures model can account for within-person correlation. Which approach is appropriate depends on the trial’s actual design and analysis plan.

The registry record labels this study as crossover, but it does not report the sequence of conditions, the duration of periods, any washout, or the model used. It also does not say whether period effects, sequence effects, or carryover were assessed. Carryover is a general concern when an effect of one condition might persist into a later period. Whether it is relevant in this trial cannot be determined from the reported details. The condition-level summaries do not retain the participant-level pairing needed to independently examine these questions.

What can be concluded from the condition summaries?

The means describe average changes within each condition. They are not a reported estimate of the difference between conditions. A formal comparative analysis would ordinarily report a contrast, its uncertainty, and the statistical method used. The registry record does not report these comparative results, a confidence interval, or a p-value. Accordingly, the means should be read descriptively rather than as evidence of a statistically established difference.

The registry lists outcome sample sizes of 7.0 for each condition. These figures describe the posted outcome summaries, not necessarily the number of participants randomized, enrolled, or included in every analysis. The overall enrollment is listed as 20. The record does not describe participant flow, missing outcome data, or the analysis population. It is therefore not possible to determine from these registry entries why the listed outcome counts differ from the enrollment figure, or whether the same participants contributed to all condition summaries.

How should planning illustrations be understood?

Any sample-size illustration based on an observed effect is a planning exercise, not a measure of the trial’s achieved power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Such calculations can help explore what a future study might require under stated assumptions. They do not show that the completed trial had a particular probability of detecting an effect, and they do not replace the trial’s own design rationale.

The registry record does not report a sample-size justification or a statistical analysis plan. It does not identify any planned interim analyses, multiplicity procedures, or model specifications. General statistical principles can clarify what those methods would address, but the actual choices for this trial are not reported in the registry record. No unadjusted re-calculation is available in the reported details, and there is no basis for substituting an independently reconstructed comparison for the sponsor’s own analysis.

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("Caloric Restriction and High Protein", "Caloric Restriction and Normal Protein", "Energy Balance")
n   <- c(7, 7, 7)
m   <- c(-63.4, -77.6, -47.4)
sp  <- c(58.2, 100.1, 41.7)
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  Caloric Restriction and High Protein  7  -63.400  153.983  -205.810  79.010
CARM  Caloric Restriction and Normal Protein  7  -77.600  264.840  -322.536  167.336
CARM  Energy Balance  7  -47.400  110.328  -149.436  54.636

11. Multiplicity, Missing Data and Analysis Populations

The record lists eight outcome measures, including the primary change in resting metabolic rate and four named secondary outcomes. It does not report a multiplicity strategy, such as whether testing across multiple outcomes was adjusted or whether some outcomes were considered exploratory. As a general statistical issue, testing several outcomes can increase the chance of at least one apparently unusual result when each is considered separately. The registry record does not provide the information needed to assess how that issue was handled.

Missing-data procedures are also not reported. The primary outcome summaries list 7.0 observations in each condition, while enrollment is listed as 20. These figures do not establish why observations may be unavailable, whether missingness occurred, or how any missing values were treated. The record does not report participant flow, withdrawals, exclusions, or an imputation method.

The analysis population is not reported in the registry record. It is therefore unclear whether the summaries represent all randomized participants, participants who completed specified conditions, or another analysis set. No statistical analysis entries are listed, and no analysis model or plan is reported. These omissions limit evaluation of the handling of repeated observations in the crossover design, the outcome denominators, and the potential for selective emphasis among outcomes. They should be treated as reporting gaps, not evidence that a particular procedure was or was not used.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events as zero in each of the three listed groups. The corresponding numbers at risk are 11 for caloric restriction and high protein, 9 for caloric restriction and normal protein, and 9 for energy balance. Deaths are reported as zero for all three groups. No serious adverse-event terms are listed.

Other adverse events are reported as 1 among 11 at risk in the high-protein caloric-restriction group, 0 among 9 at risk in the normal-protein caloric-restriction group, and 1 among 9 at risk in the energy-balance group. These are registry counts, not comparative estimates. The record does not describe event definitions, severity criteria for other events, attribution, or the period during which participants were monitored.

The adverse-event denominators differ from the outcome-summary sample sizes. Because the trial is labeled crossover, the group counts should not be interpreted as counts of distinct participants across the entire study, and they should not be added together. The registry record does not explain how safety exposure or participants at risk were assigned across conditions. Zero reported serious events is a description of the posted record; it does not establish that an intervention is free of risk.

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

The registry’s primary outcome summaries describe negative mean changes in resting metabolic rate for all three conditions over the stated baseline-to-day-6 timeframe. The reported means are -63.4 kcal with caloric restriction and high protein, -77.6 kcal with caloric restriction and normal protein, and -47.4 kcal with energy balance. Each estimate is accompanied by a standard error. These summaries characterize the reported average changes, but they do not establish a reliable difference between conditions.

The record does not report a comparative estimate, confidence interval, or p-value for the primary outcome. It therefore does not support a claim that one condition produced a statistically distinguishable change from another. Nor do the condition-level means reveal the range of responses among individual participants. The crossover label further means that an appropriate comparison may rely on within-participant information that cannot be recovered from the summaries alone.

The trial’s stated purpose concerns metabolic and anabolic hormones during caloric restriction, while the registered primary endpoint is resting metabolic rate. The posted primary summaries cannot answer every question about hormone suppression, bone, skeletal muscle, or anabolic sensitivity. Four secondary outcomes are listed, but their results are not reported in the registry record.

These results also do not establish what would occur in other populations, over other timeframes, or under conditions not described in the record. The participant characteristics, adherence details, outcome measurement protocol, and analysis population are not reported in the registry record. The sensible interpretation is consequently narrow: these are descriptive condition-level summaries from the registered endpoint, with substantial uncertainty in the reported means and no posted inferential comparison.

As a general principle, a lack of a reported statistical comparison is not equivalent to evidence that conditions are the same. Conversely, different-looking means do not establish that a true difference exists. Those conclusions require an appropriate analysis and its uncertainty, neither of which is available in the reported results.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it combines randomized treatment conditions with a crossover design and a continuous metabolic endpoint. In general, crossover studies can use within-person comparisons, which may account for stable differences between participants. That potential advantage depends on having appropriate information about condition sequence, periods, and repeated measurements, as well as an analysis that reflects the design.

The registry record illustrates why condition-level averages are not enough to reconstruct such a comparison. It reports means and standard errors for each condition, but not participant-level paired outcomes, a model-based contrast, or an uncertainty interval for the contrast. The summaries therefore describe the endpoint without showing the statistical evidence for a difference between conditions. Readers should distinguish a set of descriptive averages from a reported analysis of the randomized comparison.

The study also lists several outcomes spanning metabolism, body composition, fitness, and perceived hunger. That breadth makes clear why an analysis plan and transparent reporting of multiplicity decisions matter. The registry record does not report those decisions or results for the secondary outcomes. Their absence limits assessment of how the range of measured questions was handled.

Finally, the sample-size illustrations associated with this type of record are planning tools based on stated assumptions, not observed power. In a small study, estimates can be imprecise, but the record does not provide a design justification that would show what effect size the study was intended to detect. The statistical value of the record is thus in clarifying the endpoint, design labels, posted summaries, and remaining uncertainty—not in establishing a comparative conclusion that is not reported.

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.

Several trial-specific details needed to assess the primary outcome are not reported in the registry record. The method used to measure resting metabolic rate, the timing and conditions of measurement, and the approach to calculating change are not described. The registered timeframe is baseline and day 6, but the record does not provide further assessment details.

The crossover label is not accompanied by the condition order, period duration, washout information, or analysis of sequence, period, or carryover effects. The identity of the masked party is also not reported. These gaps prevent a detailed assessment of how the design was implemented and how it informed the primary comparison.

Participant characteristics, eligibility criteria, adherence, and the handling of deviations are not reported in the registry record for this analysis. Enrollment is listed as 20, while each primary condition summary lists 7.0 observations. The registry record does not explain participant flow or the relationship between these counts. The safety at-risk counts differ from the outcome-summary counts, and their derivation is not explained.

The registry lists four secondary outcomes and eight outcome measures overall, but only the primary outcome summaries are included in the registry record. Results for the secondary outcomes, a statistical analysis plan, missing-data procedures, multiplicity handling, and the analysis population are not reported in the registry record. There are no posted comparative estimates or confidence intervals for the primary endpoint. These limitations constrain interpretation of both precision and comparative effect; they do not, by themselves, indicate the direction of any unreported result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Caloric Restriction and Protein Intake on Metabolism and Anabolic Sensitivity — NCT02945410.
• Registry record last updated 2019-12-19; status last verified 2019-12.
• Results first posted 2019-12-19.
• 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 randomized, single-masked crossover trial sponsored by University of Nebraska Lincoln. It lists enrollment of 20 and compares caloric restriction with high protein, caloric restriction with normal protein, and energy balance. The primary endpoint is mean change in resting metabolic rate from baseline to day 6, measured as kcal change.

Reported mean changes are -63.4, -77.6, and -47.4 for the three conditions, respectively, with standard errors of 58.2, 100.1, and 41.7. The record does not report a comparative statistical analysis for this outcome. Four secondary outcomes are listed, but their results are not reported in the registry record.

Serious adverse events and deaths are reported as zero in each listed group. Other adverse-event counts are 1, 0, and 1, with the corresponding at-risk counts recorded separately. Important details about the crossover implementation, analysis plan, missing data, and analysis population are not reported in the registry record.