Expression of Longevity Genes in Response to Extended Fasting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Expression of Longevity Genes in Response to Extended Fasting (NCT01059760), a randomized na study. The primary outcome is Change From Baseline in Participant Glucose When Fasting and Fed.

2. Clinical Question

3. Trial Design

The registry describes a randomized, unmasked crossover study, with a reported enrollment of 30 and a completed status. The study began in 2010-01 and had primary completion in 2010-08. Interventions are classified as behavioral. The sponsor is Intermountain Health Care, Inc. The phase is recorded as NA.

In a crossover design, participants can experience more than one study condition in an assigned order. Here, the record names a fasting-first sequence and a fed-first sequence. The fasting-first description specifies water-only fasting for 28±4 hours followed by 28±4 hours fed; the fed-first description specifies 28±4 hours fed followed by 28±4 hours of fasting. These descriptions identify the order and approximate duration of the periods, but do not provide details about how outcomes were measured at each period or how the crossover structure was handled in the analysis.

The primary outcome is glucose change from baseline, with a timeframe of baseline and 3 days. The registry also lists 34 outcome measures, but the names and results of additional outcomes are not set out in the record summarized for this result. No secondary outcome results are posted. The record does not report a washout interval, the randomization procedure, allocation concealment, participant flow, or details of deviations from the assigned sequence. These omissions limit assessment of implementation and analysis; they do not establish that any particular procedure was or was not used.

The posted glucose results give a baseline mean and separate mean changes while fasting and when fed. The comparison results then contrast each change summary with the baseline summary. Because those are not a direct fasting-versus-fed comparison, they should not be read as estimating the difference between the two conditions in a crossover analysis. The registry record does not report the trial's original statistical analysis plan.

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

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 From Baseline in Participant Glucose When Fasting and Fed, measured over Baseline and 3 days.

The primary endpoint is the change from baseline in participant glucose when fasting and when fed. Glucose is a continuous measurement reported in mg/dL. The registry summarizes it using the mean and standard deviation, and identifies the timeframe as baseline and 3 days. The posted values are a baseline mean of 83.3 with a standard deviation of 15.8, a mean change while fasting of -8.0 with a standard deviation of 15.4, and a mean change when fed of 5.9 with a standard deviation of 16.6. Each summary is recorded with 30.0 observations.

Change from baseline is used to describe how a measurement differs from its starting value. For a continuous outcome, a mean change describes the average direction and size of the recorded changes, while a standard deviation describes how dispersed the individual measurements or changes are around their mean. The registry record does not define the calculation of change in further detail, such as the exact measurement timing within the stated timeframe.

The endpoint is glucose, not a direct measure of longevity-gene expression. Although the study title refers to expression of longevity genes, the primary outcome reported for this result concerns glucose. The record does not provide a direct statistical contrast between fasting and fed changes, so these summaries alone do not quantify the difference between those conditions.

7. Results Posted in the Registry

• Change While Fasting: mean -8.00 versus 83.30 on control; difference -91.30 (95% CI -99.20 to -83.40), standardized effect d = -5.85; z-test p = <0.001.
• Change When Fed: mean 5.90 versus 83.30 on control; difference -77.40 (95% CI -85.60 to -69.20), standardized effect d = -4.78; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

For a continuous outcome, the mean is the arithmetic average of the recorded values. It gives a compact description of the central level of the measurements or changes. The standard deviation describes how spread out those values are around the mean. It is a measure of variability among the recorded observations, not a measure of uncertainty in the estimated mean. A mean can be similar across groups or conditions while the amount of individual variation differs.

In this record, glucose is summarized by a baseline mean and standard deviation and by mean changes for fasting and fed conditions with their standard deviations. Those summaries show the average values and the spread reported for each outcome summary. They do not, by themselves, show the distribution of participant-level changes, whether values are skewed, or how paired measurements relate to one another.

What do the mean differences compare?

A mean difference is an estimate formed by contrasting two means. The meaning depends on which means are compared and their order. The registry comparison results name baseline as the comparator and report one comparison for change while fasting and another for change when fed. Their estimates are -91.3 and -77.4, respectively. Thus they are baseline-versus-change comparisons, not a direct contrast of the fasting change with the fed change.

This distinction matters in a crossover study. The clinical question concerns conditions experienced in an assigned sequence, and measurements may be related because they come from the same participants. A direct comparison of fasting and fed changes would need to use the relationship between those measurements or otherwise account for the study design. An analysis that treats summaries as independent may not reflect that relationship. The registry record does not report the method used to account for repeated measurements, sequence, or period.

The comparison estimates have corresponding intervals and p-values. The p-values are reported as p < 0.001 for both comparisons. They address the statistical contrast that was calculated, not a different contrast that was not reported. A p-value is not the probability that a hypothesis is true, and it does not measure the size or practical importance of an effect. Interpreting it requires knowing the null hypothesis and the assumptions used to calculate it.

What does an interval add?

An interval around an estimate conveys uncertainty about the comparison, under the method's assumptions. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. The record gives endpoints for the intervals, but does not state their confidence level or the method used to construct them. Therefore, the endpoints can be described as reported intervals, but their nominal coverage cannot be verified from the registry record.

Intervals should be interpreted for the specific estimand they accompany. Here, the reported intervals accompany comparisons with baseline. They do not give an interval for the difference between fasting and fed changes. Nor do they account for any crossover-specific structure unless that was incorporated in the calculation; the registry record does not say whether it was.

What does the crossover structure imply for analysis?

In a crossover study, condition order and within-participant measurements can matter. An analysis can account for paired observations and may consider period or sequence effects, depending on the design and the statistical plan. The record identifies randomized sequences but does not report the planned model, assumptions, handling of period effects, or a washout interval. Those details are not reported in the registry record. It would therefore be inappropriate to assume that a particular crossover method was used.

The posted outcome summaries each carry 30.0 observations, while the adverse-event risk sets are reported separately by sequence. The record does not explain whether all participants contributed outcome data in both conditions, whether any values were missing, or how the outcome analysis population was defined. Equal reported observation counts do not establish that there were no missing measurements or that all randomized participants were analyzed in the same way.

How should the reported statistical evidence be read?

The registry comparison results are unadjusted comparisons of posted summary statistics. The record reports no analysis records, and does not provide a full statistical analysis plan, model specification, or adjustment procedures. The comparison results should therefore be read as the particular estimates, intervals, and p-values posted, rather than as proof that all features of randomization and crossover were represented.

Effect-size standardizations are also listed with the comparisons, but standardized estimates do not change the identity of the comparison. A standardized baseline-versus-change estimate remains a baseline-versus-change comparison; it does not become a fasting-versus-fed contrast. Standardization can help express a difference in relation to variability, but its interpretation depends on the selected standard deviation and the study design. The registry record does not report a rationale for the standardization choice.

General statistical principle: when a study makes multiple outcome comparisons, the chance of at least one apparently unusual result can increase if each is assessed separately. Methods such as prespecified outcome hierarchies or multiplicity adjustments can address that issue, but the registry record does not report such methods. The fact that no secondary outcome results are posted does not establish how many analyses were conducted or planned.

Finally, a statistically small p-value does not establish clinical relevance, causal attribution, or generalizability. Those judgments require context about the outcome, the target population, the design, and the analysis. The registry record is informative about the posted glucose summaries and their baseline comparisons, but leaves important design and analysis details unreported.

10. Confidence Intervals and Precision

The posted comparison for change while fasting has an estimate of -91.3 and an interval from -99.2 to -83.4. The comparison for change when fed has an estimate of -77.4 and an interval from -85.6 to -69.2. Both p-values are reported as p < 0.001. These interval endpoints describe the precision of the baseline comparisons as reported; they do not describe a direct comparison between fasting and fed changes.

An interval gives a range of values compatible with an estimate under the calculation's assumptions. Greater width means more uncertainty about the estimate, while less width indicates greater precision. The interval's practical interpretation also depends on what parameter was estimated and how the interval was constructed. The registry record does not report the interval confidence level or construction method, so those features cannot be checked against the stated design.

The standard deviations for the baseline, fasting-change, and fed-change summaries are 15.8, 15.4, and 16.6, respectively. These describe variability in the reported outcome summaries, not the precision of the comparison estimates. Although each glucose summary is listed with 30.0 observations, the record does not explain whether those values are paired participant measurements or how their within-participant correlation was handled. That information can be important for precision in a crossover study.

The registry comparison intervals are relatively far from zero, and their reported p-values are small, but that does not resolve the question of whether fasting and fed changes differ. Precision must be judged for the question actually estimated. Since the record does not provide an interval for a direct fasting-versus-fed contrast, the precision of that contrast is not reported in the registry record.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed comparison effects, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. For each comparison, the planning rows consider detecting 100%, 75%, or 50% of the observed effect. The trial's own original design assumptions are not reported in the registry record.

For the baseline comparison with change while fasting, planning for 100% of the observed effect gives 1 participant per arm for 80% power and 1 participant per arm for 90% power. Planning for 75% gives 1 and 2 participants per arm, respectively; planning for 50% gives 2 and 3 participants per arm. For the baseline comparison with change when fed, planning for 100% gives 1 participant per arm for 80% power and 1 participant per arm for 90% power. Planning for 75% gives 2 and 2 participants per arm, and planning for 50% gives 3 and 4 participants per arm.

The 80% power column describes the planned sample size under which the assumed effect would be detected at the stated significance level with 80% probability, if the planning assumptions held. The 90% column uses a higher target probability of detection under those same assumptions. The figures are not evidence about the trial's actual probability of finding an effect. This is not observed power.

Smaller effects generally require more participants to detect reliably than larger effects, which is why planning for a smaller fraction of the observed effect gives larger figures in these rows. These calculations use the posted baseline comparisons, not a direct fasting-versus-fed contrast, and the registry record does not report the original design calculation. They should not be used to infer the sample size needed for a different estimand or analysis.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -91.300; pooled standard deviation σ = 15.601.
2. n = 2 × (1.96 + 0.842)² × 15.601² / -91.300² = 0.5, rounded up to 1 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -91.3                      # observed difference in means
sigma <- 15.6012819986051                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1059760)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1 (80% power), 1 (90% power)
 75% of observed effect: n per arm = 1 (80% power), 2 (90% power)
 50% of observed effect: n per arm = 2 (80% power), 3 (90% power)
power.t.test: 2 
Simulated power at n = 1 per arm: NA (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 34 outcome measures, but no secondary outcome results are posted. It also reports no analysis records. These registry entries do not identify how many statistical tests were planned or conducted, what outcomes were designated primary in the original analysis plan, or whether any multiplicity procedure was used. The multiplicity plan is not reported in the registry record.

Multiplicity refers generally to the interpretive problem created by examining multiple outcomes or comparisons. If many tests are treated as separate opportunities to find evidence, the chance of at least one small p-value can increase. Prespecification and adjustment methods can help control that issue, but the record does not describe such choices. The two posted p-values should therefore be understood as reported for their respective baseline comparisons, without assuming adjustment or assuming that no other analyses occurred.

Missing-data handling is also not described. The glucose summaries each report 30.0 observations, but this alone does not explain how missing measurements were treated, whether participants contributed measurements to both conditions, or whether any observations were excluded. The registry record does not report an imputation method, a missingness assessment, or a sensitivity analysis.

The analysis population is not reported in the registry record. It does not state whether the outcome summaries use all randomized participants, those who completed both periods, or another defined population. The record describes randomized sequences, but gives no participant-flow detail for the glucose outcome. It also does not report whether the statistical analysis accounted for period, sequence, or participant-level pairing in the crossover design. These omissions limit assessment of the extent to which the posted comparisons reflect the randomized design.

14. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures are reported by assigned sequence. In the fasting-first group, 0 serious adverse events are recorded among 16 participants at risk. In the fed-first group, 0 serious adverse events are recorded among 14 participants at risk. The registry lists no serious-event terms. This means no serious events are entered in these record fields; it does not establish what monitoring or event-collection procedures were used.

Other adverse events are recorded for 2 of 16 participants at risk in the fasting-first group and 1 of 14 in the fed-first group. These are counts, not percentages, and the registry record does not provide further descriptions of the events in the information reported for this result. The groups represent the reported sequence categories; the record does not clarify all details of exposure or event timing.

Deaths are not reported in the registry record. A missing death value should not be read as zero deaths. These event counts are descriptive and do not establish a comparative safety effect. In particular, the record does not provide an analysis of adverse-event differences or details about event definitions and ascertainment.

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

The result establishes what the registry record reports for glucose: a baseline mean of 83.3 mg/dL, a mean change while fasting of -8.0 mg/dL, and a mean change when fed of 5.9 mg/dL, each with its standard deviation and observation count. It also reports two baseline comparisons, both with p < 0.001 and with the stated intervals. These values describe the posted outcome summaries and comparisons.

The result does not provide a direct estimate of the difference between fasting and fed changes. The posted comparison estimates use baseline as the comparator, so they cannot be interpreted as a randomized contrast between the two periods. The registry record also does not give enough detail to confirm how repeated participant measurements, sequence, or period were handled in an analysis.

The study title refers to expression of longevity genes, while the primary outcome reported for this result is glucose change. The glucose findings therefore do not by themselves establish a change in gene expression. The registry record does not provide gene-expression results in the primary outcome information, and no conclusions about other outcomes should be inferred from the glucose summaries.

The findings also do not establish that a result is clinically important or applies beyond the recorded study population. Participant characteristics and eligibility details are not reported in the registry record. The posted p-values do not quantify clinical importance, and the confidence level and construction method for the intervals are not stated.

In practical statistical terms, the record offers descriptive evidence about glucose summaries and unadjusted baseline comparisons, but leaves the direct fasting-versus-fed question unanswered in its posted comparisons. Its limitations are not evidence that the study did or did not conduct additional analyses; those details are simply not reported in the registry record.

16. Why This Trial Matters Statistically

This trial is statistically notable because its crossover design makes the distinction between sequence, condition, and comparator especially important. Participants were assigned to fasting-first or fed-first sequences, while the primary question concerns glucose changes under fasting and fed conditions. The posted comparison results contrast each change summary with baseline rather than comparing the two changes directly. Clear identification of the estimand—the specific quantity an analysis is intended to estimate—is essential for understanding what a result means.

The distinction also illustrates why repeated measurements need careful treatment. In a crossover study, measurements from the same participant may be related. A direct analysis can use that paired structure, but the registry record does not report whether or how it was accounted for. Without a stated analysis model, readers cannot assess the implications of participant-level correlation, period, or sequence for the estimates and their precision.

The study also demonstrates why a small p-value is not a complete statistical interpretation. Both posted comparisons have p < 0.001, but they answer baseline-comparison questions rather than the direct fasting-versus-fed question. The estimand, assumptions, uncertainty, and relevance all matter alongside a p-value.

Finally, the contrast between the study title and its reported primary endpoint is important for interpreting scope. The primary result described is glucose change, while the title refers to longevity-gene expression. A result for one outcome should not be treated as evidence about another outcome. The registry record's missing information about the analysis plan and other outcome results further limits what can be concluded statistically.

17. 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 that the posted comparisons do not directly estimate the difference between glucose change while fasting and glucose change when fed. Each comparison uses baseline as the comparator. Consequently, the strikingly different-looking numerical summaries cannot be treated as a direct condition contrast, and the posted p-values do not answer that contrast either.

The registry record identifies a randomized crossover design but does not report how the analysis accounted for repeated measurements within participants, treatment order, or period. It does not report a washout interval or enough measurement-timing detail to assess possible carryover or period effects. These are unreported design and analysis details, not evidence that such procedures were absent.

Participant characteristics, eligibility criteria, recruitment details, and the outcome analysis population are not reported in the registry record. Nor does it describe missing-data handling, participant flow, adherence, or exclusions. Although the glucose summaries each list 30.0 observations, that does not establish how measurements were distributed across conditions or how the crossover data were assembled.

The interval confidence level and calculation method are not stated. The original sample-size rationale and statistical analysis plan are also not reported. The planning illustrations use observed baseline-comparison effects and do not establish the assumptions used when the trial was designed. The record lists 34 outcome measures but posts no secondary outcome results, limiting assessment of outcomes beyond glucose and of any multiplicity approach.

Finally, the primary outcome is glucose, while the title concerns longevity-gene expression. The reported glucose result cannot substitute for an outcome-specific analysis of gene expression. The registry record does not provide enough information in the reported primary outcome to assess that separate question.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Expression of Longevity Genes in Response to Extended Fasting — NCT01059760.
• Registry record last updated 2017-07-17; status last verified 2011-03.
• Results first posted 2017-07-17.
• 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.

21. Record Summary

NCT01059760 is a completed, randomized, unmasked crossover study titled “Expression of Longevity Genes in Response to Extended Fasting.” The record lists cardiovascular disease as the condition, enrollment of 30, and behavioral fasting-first and fed-first sequences. The study began in 2010-01 and reached primary completion in 2010-08.

The primary outcome is change from baseline in participant glucose when fasting and fed, measured in mg/dL over a timeframe described as baseline and 3 days. The record reports baseline, fasting-change, and fed-change means with standard deviations. Its comparison results contrast each change summary with baseline; they do not report a direct fasting-versus-fed estimate.

The registry lists 34 outcome measures, no posted secondary outcome results, and no analysis records. It does not report the original analysis plan, missing-data approach, or crossover-specific analysis details. No serious adverse events are recorded in either sequence group; deaths are not reported in the registry record.