High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders (NCT01494051), a randomized phase 1, phase 2 study. The primary outcome is Energy Expenditure.

2. Clinical Question

The study also aimed to determine whether a higher-protein diet altered body composition, energy balance, and metabolic control. The registry record identifies body composition as a secondary outcome. It describes measurements of resting energy expenditure using indirect calorimetry, estimates of substrate oxidation using indirect calorimetry results and urine urea nitrogen excretion, and measurement of total energy expenditure using doubly labeled water.

The trial was randomized, with participants assigned to parallel diet groups. The posted primary outcome summaries list a mean of 2045.0 kcal with a standard deviation of 273.0 for the high-carbohydrate group, and a mean of 2343.0 kcal with a standard deviation of 507.0 for the high-protein group. The registry record does not include an inferential comparison for these summaries, so the question of whether the groups differed statistically cannot be answered from the posted values alone.

3. Trial Design

This was a randomized, parallel-group Phase 1 and Phase 2 study sponsored by Oregon Health and Science University. The registry record lists the study as completed, with an enrollment of 13. The study start is recorded as 2006-01, and primary completion as 2009-09. Masking is listed as none, so the record describes an unmasked comparison.

The two diet groups differed in the balance of protein and carbohydrate. Both diet descriptions specify 10% long-chain fatty acids and 20% medium-chain triglycerides. The high-carbohydrate diet contained 12% protein and 68% carbohydrate; the high-protein comparison diet contained 25% protein and 45% carbohydrate. The registry describes diet counseling as the behavioral intervention. It does not report further details of how counseling was delivered, how adherence was assessed, or whether participants followed additional dietary instructions.

The posted primary outcome concerns energy expenditure, with a timeframe described as change from baseline after 4 months of treatment. The record describes several measurement approaches: indirect calorimetry for resting energy expenditure, indirect calorimetry results together with urine urea nitrogen excretion to estimate substrate oxidation, and doubly labeled water for total energy expenditure. The outcome summary gives group means and standard deviations for energy expenditure. It does not provide baseline values or a group-level estimate of change from baseline, so the precise relationship between the displayed summaries and the stated change-from-baseline timeframe is not clarified in the registry record.

The record lists one secondary outcome, body composition. It states that there are two outcome measures but lists no statistical analyses. There is no reported description of the randomization procedure, allocation concealment, sample-size justification, protocol deviations, or analysis population. These details should not be inferred from the randomized designation alone. The small enrolled group and the absence of a posted inferential analysis mean that the summary is best read as a description of the recorded group outcomes, rather than as a complete report of the comparative 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.

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 Energy Expenditure, measured over change from baseline after 4 months of treatment.

The primary endpoint is energy expenditure, measured in kcal. The registry describes the comparison as a difference in energy expenditure and substrate oxidation between the high-carbohydrate and high-protein diet groups. It identifies change from baseline after 4 months of treatment as the timeframe. Resting energy expenditure was measured by indirect calorimetry, while total energy expenditure was measured using doubly labeled water. Substrate oxidation was estimated from indirect calorimetry results and urine urea nitrogen excretion.

Energy expenditure is a continuous measure: it can take a range of numerical values rather than classifying participants into categories. Group means summarize the average recorded value, while standard deviations describe how spread out individual values are around each group mean. Both can help readers understand the level and variability of the outcome, but they do not by themselves establish whether the groups differ beyond what might be expected from sampling variability.

In general, measuring energy expenditure can help characterize energy balance, one of the areas the study set out to examine. The different measurement methods address distinct aspects of expenditure or metabolism. The registry record does not report a rationale for selecting this endpoint as primary or describe how the several measurements were combined, prioritized, or analyzed. Although the posted results give group means and standard deviations, they do not include a confidence interval or a test of the between-group contrast. The summaries therefore describe the observed groups but do not quantify the precision of the comparative effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For the primary endpoint, the registry reports means and standard deviations by randomized group. A mean is the arithmetic average of the recorded values in a group. A standard deviation describes the spread of those individual values around the mean. These summaries are useful for describing the observed data, but they answer a different question from an estimate of the difference between groups. The posted mean and standard deviation for each group do not themselves provide a confidence interval or a significance test for the comparison.

What does a confidence interval add?

General statistical explanation: a confidence interval presents a range of values compatible with the data and the assumptions of the analysis. Its width conveys precision: a narrower interval indicates greater precision, and a wider interval indicates greater uncertainty. A confidence interval for the contrast between groups would be more informative about the size and precision of the comparative estimate than separate group summaries alone. No such interval is reported in the registry record, and no confidence limits are posted for either group summary.

Why is a formal contrast important?

A randomized study is designed to compare assigned groups, but the comparative question concerns the difference between their outcomes. A statistical analysis would generally define a contrast and quantify its uncertainty. Depending on the outcome and study design, that analysis could account for baseline values or other features specified in the analysis plan. The registry record does not describe a model, an adjustment strategy, or the test used for the primary comparison. It also lists zero analyses. Therefore, the posted summaries cannot be presented as the result of a reported model or as an adjusted treatment effect.

The endpoint is continuous, and the record identifies the reported parameter as a mean with standard deviation. General statistical explanation: continuous outcomes are often summarized with means when that summary is appropriate to the distribution and scientific question. A standard deviation is not the same as a standard error or confidence interval. The standard deviation describes variability among observations; a standard error describes the precision of an estimated quantity. The record does not post standard errors for the group means or for a group contrast.

What does the missing comparison mean?

The record indicates that values are missing or not estimable for a two-arm comparison of this continuous outcome. This means that a comparative result is not available in the posted analysis data used for this page. It does not explain why the comparison could not be estimated, and readers should not infer the reason. In particular, the registry record does not say whether the obstacle involved the data, the analysis, or reporting. The sponsor’s own analysis is not reported, so there is no sponsor analysis to take precedence over a recalculation.

General statistical explanation: a difference between two sample means can sometimes be recalculated from the group summaries, but such a simple calculation would not replace an analysis that accounts for the study’s planned estimand, baseline measurements, or any prespecified model. No recalculated comparison is shown because the record marks the two-arm comparison as not estimable. Any calculation based only on summary values would also depend on assumptions that are not documented in the registry record. It would be inappropriate to treat an unadjusted reconstruction as if it were the trial’s own analysis.

How should variability be considered?

The standard deviation is larger in the high-protein group summary than in the high-carbohydrate group summary. General statistical explanation: when outcome values vary substantially, a group mean may be estimated less precisely, particularly when the amount of information is limited. The mean and standard deviation alone do not show whether the distribution is symmetric, whether outliers are influential, or whether the assumptions of a particular statistical model are met. Distribution plots or individual observations might help assess those features, but they are not described in the registry record.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If an analysis ignores that extra variability, standard errors and confidence intervals can be too optimistic. This concept is most relevant when the analysis model makes a variance assumption; the registry record does not report a model or evidence of over-dispersion in this trial. It is therefore a general methodological consideration, not a finding about these data.

What can planning illustrations tell us?

General statistical explanation: sample-size planning uses assumptions about the effect to detect, variability, allocation, and the desired statistical criteria. The planning description associated with this record specifies a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; it describes the effect to detect as a stated fraction of the observed effect. Such figures, if displayed elsewhere on the page, are planning illustrations rather than observed outcomes or evidence that the study had a particular probability of finding a result. They are not the trial’s own design justification. The registry record does not report the trial’s sample-size justification, and a planning calculation should not be described as observed power.

For continuous outcomes, sample-size planning also depends on a measure of variability and on the chosen effect size. The record does not report a formal primary comparison, so any illustration based on an observed effect should be interpreted cautiously and should not be confused with a trial analysis. The distinction is especially important when a comparative effect is unavailable or not estimable in the registry results.

Finally, interpretation depends on knowing what was analyzed. The record lists enrollment and group summary counts, but it does not report whether all randomized participants contributed to the endpoint summaries, how missing observations were handled, or whether the analysis followed an intention-to-treat principle. Those omissions limit assessment of the estimand and the reliability of the descriptive comparison. General statistical methods can explain what information would be useful, but cannot supply unreported design or analysis details.

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("High Carbohydrate Diet", "High Protein Diet")
n   <- c(6, 7)
m   <- c(2045, 2343)
sp  <- c(273, 507)
sd  <- sp      # posted standard deviations
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  High Carbohydrate Diet  6  2045.000  273.000  1758.504  2331.496
CARM  High Protein Diet  7  2343.000  507.000  1874.103  2811.897

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one secondary outcome, body composition, and two outcome measures. It does not provide results for body composition in the registry record. It lists no statistical analyses. The record does not state whether the primary endpoint included multiple component measurements, whether several comparisons were planned, or whether any strategy was used to address multiplicity. These details are not reported in the registry record.

General statistical explanation: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of the tests. Multiplicity methods can include prespecified prioritization or adjustments to the testing procedure. Without a reported analysis plan, readers cannot determine whether multiplicity was relevant to the sponsor’s analysis or how it was addressed. This is a limitation in interpretation, not evidence that a particular approach was used or omitted.

The record gives group counts for the primary outcome summaries, but it does not report participant-level missingness, reasons for missing observations, or how missing data were handled. It also does not identify the analysis population, such as all randomized participants or a defined subset. No imputation method, sensitivity analysis, or protocol-adherence population is described. The posted enrollment of 13 should therefore not be assumed to be the number analyzed for every endpoint; the primary summaries specifically list 6.0 and 7.0 participants by group.

In general, missing-data handling can affect a comparative estimate when availability of outcome data is related to participant characteristics or outcomes. Without a description of missingness and analysis populations, readers cannot assess that possibility. The registry record does not report enough information to determine whether the posted group summaries include all randomized participants or whether any exclusions occurred.

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.

The registry record lists serious adverse events for 0 of 6 participants in the high-carbohydrate group and 0 of 7 participants in the high-protein group. It also lists other adverse events for 0 of 6 and 0 of 7 participants, respectively, and records 0 deaths in each group. These are the safety counts posted in the record; no serious adverse event terms are listed.

These figures describe what is recorded in the registry, not a guarantee that no event of any kind occurred. The record does not provide additional details about event definitions, the observation period for safety collection, severity classifications beyond serious versus other events, or how events were sought and verified. It also does not describe whether participants withdrew or whether safety data were complete for every participant.

General statistical explanation: zero recorded events in a small group does not establish that the underlying risk is zero. The counts should be read alongside the limited group sizes and the lack of further safety detail. They are not a formal comparison of safety between diets, and the registry record does not report a statistical test or comparative safety estimate. The figures therefore summarize the posted event counts without establishing that either diet is safer.

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

The record is informative about the trial’s question, design, outcome measures, and descriptive primary outcome summaries. It documents a randomized comparison of two diet compositions in people with long-chain fatty acid oxidation disorders and describes the primary outcome as energy expenditure after 4 months of treatment. The posted group summaries show a mean of 2045.0 kcal (standard deviation 273.0) for the high-carbohydrate diet and a mean of 2343.0 kcal (standard deviation 507.0) for the high-protein diet.

Those results do not provide a complete estimate of the comparative effect. The registry record does not report a confidence interval, a p-value, a model, or an adjusted comparison, and the two-arm continuous comparison is marked as missing or not estimable. The outcome description refers to change from baseline, but the record does not clarify whether the displayed values are endpoint values or changes. The summaries can therefore be described as the posted group values, but their exact interpretation relative to baseline is uncertain.

These data do not establish that either diet changes energy expenditure, that the groups differ statistically, or that there is no difference. Absence of a reported comparison is not the same as evidence of no effect. Similarly, the primary outcome summary cannot answer every part of the study’s broader question about substrate oxidation, energy balance, metabolic control, or body composition. The registry describes those aims and methods, but the relevant comparative results are not reported in the information.

General statistical explanation: a study’s estimate and its precision both matter. A descriptive mean tells readers about the observed group, while a comparative estimate with uncertainty helps assess the range of effects compatible with the data. Because the latter is absent, readers should avoid treating the difference suggested by the displayed means as a definitive treatment effect. The small group summaries and substantial variability also counsel against overinterpreting the observed values.

The safety record lists no serious adverse events, other adverse events, or deaths in either group. That is a description of recorded events, not proof that risk is absent. The registry record does not provide the additional safety details needed for a broader safety assessment. Overall, the posted information supports a cautious account of what was measured and summarized, but not a conclusion about whether one diet is superior or whether either diet works.

14. Why This Trial Matters Statistically

This trial illustrates a recurring challenge in clinical research reporting: a registry may describe a carefully framed question and provide group-level outcome summaries without posting the comparative analysis needed to answer that question. Here, the trial is randomized and compares two diet compositions, but the primary outcome comparison is marked as missing or not estimable, and no statistical analyses are listed. That gap separates descriptive reporting from inference.

The record also highlights why outcome definitions and analysis details matter. The primary endpoint is described as change from baseline after 4 months, yet the posted summaries do not clarify whether they are endpoint values or changes. The measurement description includes resting energy expenditure, total energy expenditure, and estimates of substrate oxidation. Readers need to know which measurement underlies each reported result and how it maps to the primary estimand. The registry record does not provide that full account.

Small groups and variable outcomes make precision especially important to communicate. Group means and standard deviations are useful, but a comparative estimate and uncertainty interval would better show what the data can support. In their absence, readers should not use the apparent difference in means as a substitute for an inferential result. Nor should a sample-size planning illustration be mistaken for observed power or for the study’s original sample-size justification.

The study is also a reminder that interpretation depends on transparent reporting of missing data, analysis populations, and multiplicity. These details are not reported in the registry record. Their absence does not demonstrate that the underlying conduct was deficient, but it limits independent statistical assessment. Clear reporting of these elements would help readers distinguish the observed summaries from the trial’s intended and analyzed treatment effect.

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 principal limitation for interpreting this trial is that the registry record does not report a formal comparison of the primary outcome. Although it provides group means, standard deviations, and participant counts, it lists no analyses and marks the two-arm continuous comparison as missing or not estimable. There is no confidence interval or p-value with which to assess the precision or statistical evidence for a group contrast.

The primary outcome timeframe is described as change from baseline after 4 months, but the posted summaries do not identify whether the values represent changes or values at the endpoint. Baseline measurements and change estimates are not reported. The record also does not describe whether the comparison was adjusted for baseline or analyzed using another model.

The group summaries include 6.0 participants for the high-carbohydrate diet and 7.0 for the high-protein diet, while total enrollment is 13. The registry record does not say whether the endpoint analysis included all randomized participants, how any missing measurements were handled, or whether exclusions occurred. The study’s sample-size justification and detailed analysis plan are not reported either.

The registry describes multiple measurements related to energy expenditure and substrate oxidation, but the available primary summary does not provide comparative results for all of them. Body composition is listed as a secondary outcome, without a result in the information. The record does not state how multiplicity was handled or how the various measurement results were prioritized.

Finally, the safety entries are limited to event counts and do not include details about event definitions, ascertainment, or the safety observation period. These reporting gaps restrict the conclusions that can be drawn from the registry record. They do not establish that the study had problems in conduct; they identify information that is not available for independent assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders — NCT01494051.
• Registry record last updated 2020-04-29; status last verified 2020-04.
• Results first posted 2020-04-21.
• 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

This completed, randomized, unmasked, parallel-group Phase 1 and Phase 2 study compared diet counseling for a high-carbohydrate diet with counseling for a high-protein diet in people with long-chain fatty acid oxidation disorders. The registry lists enrollment of 13 and identifies energy expenditure as the primary outcome, with a timeframe of change from baseline after 4 months of treatment.

The primary outcome summaries report means of 2045.0 kcal (standard deviation 273.0; 6.0 participants) for the high-carbohydrate group and 2343.0 kcal (standard deviation 507.0; 7.0 participants) for the high-protein group. The registry record lists no analyses and indicates that values for a two-arm continuous comparison are missing or not estimable. It does not report a confidence interval, p-value, or explanation of whether the displayed means are changes from baseline.

Body composition is listed as a secondary outcome, but its result is not reported in the registry information. The safety entries list no serious adverse events, other adverse events, or deaths in either group. These descriptions summarize the posted record; they do not establish a comparative treatment effect or a complete safety assessment.