Is Non-Cardiac Chest Pain Caused by Sustained Longitudinal Smooth Muscle Contraction?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Is Non-Cardiac Chest Pain Caused by Sustained Longitudinal Smooth Muscle Contraction? (NCT01839058), a registered phase not stated study. The primary outcome is Mean Change in Esophageal Length With Acid.

2. Clinical Question

The study asks whether acid is associated with esophageal shortening in people with non-cardiac chest pain, and whether that response differs from the response in healthy controls. Its stated rationale is that sustained contractions of longitudinal smooth muscle may be related to non-cardiac chest pain. The investigators’ hypothesis was that at least a subset of patients would show an exaggerated shortening response to acid that correlates with symptom production.

The registry also lists secondary questions about esophageal length when symptoms begin, length at maximal symptom intensity, and whether symptom onset correlates with shortening. These are planned questions, not findings: numerical results for them are not reported in the registry record. The record likewise does not report a correlation estimate or the number of participants for whom such a correlation was found.

3. Trial Design

NCT01839058 is recorded as a completed study sponsored by Queen’s University. The registry lists a start date of 2013-10 and a primary completion date of 2014-10, with enrollment of 40. The listed condition is Chest Pain Atypical Syndrome. Completion status indicates the registry’s recorded status; it does not establish that every planned measurement or analysis was reported.

The study description outlines a prospective evaluation of esophageal shortening responses to acid in patients with non-cardiac chest pain and controls. The intervention is listed as esophageal manometry. The patient group is described as people whose chest pain has had coronary artery disease formally ruled out; the control group is described as healthy volunteers without esophageal symptoms. The brief summary describes high-resolution esophageal manometry coupled with acid infusion.

The registry does not state that participants were randomly assigned, and its record identifies the arms as not a like-for-like control comparison. The groups differ by their stated eligibility characteristics, so a difference between them would not automatically isolate an effect caused by chest pain status or by acid. Details such as the recruitment procedure, participant flow, treatment sequence, blinding, and actual measurement procedures are not reported in the registry record.

The primary endpoint is a continuous measure of esophageal length. The registry defines its summary as a mean with standard deviation and gives a timeframe of length at T= 20 minutes minus baseline (T=0). The endpoint description also characterizes the measure as mean esophageal length with acid infusion minus mean length with saline infusion. The record does not clarify how these descriptions were operationalized together.

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 Mean Change in Esophageal Length With Acid, measured over Length at T= 20 minutes - Baseline (T=0).

The primary endpoint is titled “Mean Change in Esophageal Length With Acid” and is measured in centimeters. The registry specifies a mean and standard deviation and gives the timeframe as length at T= 20 minutes minus baseline (T=0). Its description says the measure is mean esophageal length with acid infusion minus mean length with saline infusion.

Esophageal length is used as a quantitative indicator of shortening: a change in length can describe the physical response being investigated. A mean expresses the average measurement in a group or condition, while the standard deviation describes how spread out individual measurements are around that mean. These are general interpretations of the stated summary measures, not claims about results from this study.

The endpoint wording contains two pieces that should be kept distinct. The timeframe names a comparison between a measurement at T= 20 minutes and baseline at T=0; the description names acid infusion relative to saline infusion. The registry record does not explain whether the endpoint combines those comparisons or how the measurements were calculated. It also does not report the group means, standard deviations, number of observations contributing to the endpoint, or an estimate of the difference between groups.

The endpoint could address the study’s physiological question if reported with appropriate uncertainty and enough procedural detail. Without numerical results, however, it cannot show the magnitude, direction, or precision of any acid-associated change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure summarized by a mean and standard deviation. It does not report the numerical estimates or explain the analysis used to produce them. The concepts below are general explanations of how such methods are commonly interpreted; they should not be read as confirmation that a particular procedure was used in this study.

What does a mean describe?

For a continuous measurement such as esophageal length, the mean describes the average across the observations included in a group or condition. It gives a compact description of the center of the measured values. A mean alone does not show whether most observations are close to that center or whether the data include substantial variation.

The standard deviation describes the spread of observations around the mean. It is a measure of variability among observations, not a measure of uncertainty in the estimated mean. Uncertainty in a mean or a contrast is usually conveyed with a confidence interval or another inferential measure. The registry names standard deviation as the dispersion measure but does not report a confidence interval or standard error for the endpoint.

What comparison is the endpoint meant to represent?

The endpoint title refers to mean change in esophageal length with acid. The timeframe describes length at T= 20 minutes minus baseline at T=0, while the measure description says mean length with acid infusion minus mean length with saline infusion. Those descriptions suggest comparisons involving time and infusion condition, but the registry record does not specify how they fit together. Without that clarification and the underlying result, the sign and interpretation of any numerical contrast cannot be established.

In general, a difference between two measurements is interpretable only when the measurement conditions, direction of subtraction, and analysis population are clear. A positive value can mean different things depending on which condition is subtracted from which. The registry’s wording identifies acid-minus-saline in its description, but does not fully clarify the relationship to the stated baseline-to-T= 20 minutes timeframe.

Why does uncertainty matter?

A confidence interval, in general, gives a range of values compatible with the data and the statistical method used. A narrow interval indicates greater precision than a wide interval, though precision does not by itself establish importance or causation. A p-value, in general, measures how incompatible the observed data are with a specified null model; it does not measure the probability that a hypothesis is true or the size of an effect. No confidence interval or p-value for the primary endpoint is reported in the registry record, so neither precision nor statistical evidence can be evaluated.

What can planning assumptions tell readers?

The registry describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are assumptions for planning scenarios. They are not a description of the actual allocation, and they do not establish that the study had a particular power. Sample-size calculations based on an observed effect are planning illustrations, not observed power. The observed effect and numerical planning results are not reported in the registry record.

In general, planning estimates depend on assumptions about the effect to detect, variability, allocation, and analysis. If an assumed effect is smaller, a study generally needs more participants to detect it at a chosen error rate, all else being equal. Such general relationships do not reveal the sample size needed for this study because the observed effect and variability are not reported.

Why can over-dispersion matter?

For continuous measurements, greater variability makes it harder to distinguish a group contrast from natural spread in the data. For count outcomes, over-dispersion means that variation exceeds what a simple model assumes; ignoring it can make uncertainty appear too small. This is a general statistical point, not a claim that over-dispersion occurred in this study. The primary endpoint is continuous, and the registry does not report a fitted model or diagnostic assessment.

Overall, the registry identifies a continuous endpoint and some planning assumptions, but it does not describe a full statistical analysis plan. The analysis model, handling of repeated measurements, covariate adjustment, estimation method, assumptions checks, and treatment of outlying observations are not reported in the registry record.

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("Non Cardiac Chest Pain Patients", "Healthy Controls")
n   <- c(17, 16)
m   <- c(-0.4, -0.39)
sp  <- c(0.54, 0.55)
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  Non Cardiac Chest Pain Patients  17  -0.400  0.540  -0.678  -0.122
CARM  Healthy Controls  16  -0.390  0.550  -0.683  -0.097

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the primary measure of mean change in esophageal length with acid and three secondary outcomes concerning esophageal length at symptom onset, length at maximal symptom intensity, and whether symptom onset correlated with shortening. When several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include designating a primary outcome in advance, adjusting inference across multiple tests, or interpreting secondary analyses as exploratory. The record does not report a multiplicity strategy, hierarchy among secondary outcomes, or adjustment for multiple comparisons.

The registry records zero analyses. Numerical outcome estimates and analysis results are not reported in the registry record. This absence does not show that no analysis was conducted; it means the record does not contain analysis results to evaluate.

Missing-data methods and the number of participants contributing to each outcome are not reported in the registry record. The record does not describe whether all enrolled participants completed manometry, how incomplete measurements were handled, whether any outcome values were excluded, or what analysis population was used. These omissions matter because the participants with usable measurements may not represent everyone enrolled if completion or missingness is related to symptoms or measurement results.

The record also does not report a prespecified statistical analysis plan, interim analyses, or a sample-size justification. These details should not be inferred from the planning assumptions alone. Without outcome-specific denominators, missing-data handling, and the analysis approach, readers cannot assess whether the available measurements were analyzed consistently with the original plan.

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.

For the Non Cardiac Chest Pain Patients group, the registry lists 21 participants at risk for serious adverse events and 0 affected; it also lists 21 at risk for other adverse events and 0 affected. For Healthy Controls, it lists 19 at risk for serious adverse events and 0 affected, and 19 at risk for other adverse events and 0 affected. The death count is 0 in each group.

These are the posted counts. They do not establish that there was no risk, nor do they show that the intervention is safe. Zero recorded events can occur even when an event is possible, and the counts alone do not indicate how completely events were collected or how long participants were monitored. Follow-up duration and adverse-event ascertainment procedures are not reported in the registry record.

The registry does not list serious adverse-event terms. It also does not provide event-level descriptions or clarify the definitions used for the serious and other adverse-event categories. The counts should therefore be read as registry-recorded events in the stated groups, not as a comprehensive assessment of harms or as evidence about outcomes beyond the recorded observation.

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

This study matters because it set out to examine a proposed physiological explanation for non-cardiac chest pain: acid-associated esophageal shortening and its possible relationship to symptom production. The record describes a comparison between patients with non-cardiac chest pain and healthy controls, and identifies esophageal length as the primary measurement. It also identifies symptom timing and shortening correlations as secondary questions.

What the registry record does not establish is whether the groups differed, whether acid was followed by shortening, or whether shortening tracked symptoms. Numerical outcome results are not reported in the registry record. The endpoint description and study hypothesis are not findings, and the study’s completed status does not supply the missing results.

Even a reported group difference would need cautious interpretation. The registry does not state random allocation, and the groups are not described as a like-for-like control comparison. The record therefore does not support treating a potential contrast as a randomized causal estimate. In addition, the endpoint wording does not fully clarify how baseline-to-T= 20 minutes relates to the acid-versus-saline description.

The record also cannot establish whether any physiological association is clinically important. It provides no effect estimate, uncertainty interval, or reported correlation result. Those gaps prevent assessment of magnitude, precision, consistency, and the relationship to symptoms. They do not demonstrate that an effect is absent; they leave the question unresolved in the registry record.

The appropriate reading is narrow: the registry captures a study rationale, planned groups, measurement approach, and outcome definitions, but not the numerical evidence needed to judge the stated hypothesis. No treatment recommendation or conclusion about clinical benefit follows from this record.

14. Why This Trial Matters Statistically

The trial raises a statistical question about connecting a measured physiological response with symptoms. Its primary endpoint is a continuous length measure, while the secondary outcomes include symptom timing and a correlation question. These outcomes concern related but distinct aspects of the hypothesis. A change in average length, an association with symptom onset, and a relationship between shortening and symptoms are not interchangeable findings.

This distinction is important in clinical research. A group average can describe a pattern across participants while concealing variation in individual responses. A correlation can describe whether two measurements vary together, but does not by itself establish that one causes the other. Symptom-linked measurements also require clarity about timing, measurement procedures, and which observations contribute to each analysis. The registry record does not report those analysis details or the numerical findings.

The study also illustrates why comparison-group design matters. Healthy controls without esophageal symptoms provide a reference group, but they differ by design from patients with non-cardiac chest pain. Without random allocation, a group contrast cannot automatically be attributed to a single cause. Interpretation would depend on the measured outcomes, uncertainty, and potential differences between groups.

Finally, the missing numerical results limit the statistical contribution that can be assessed from the registry. The record identifies the planned endpoint and the planning assumptions, but gives no primary effect estimate or analysis results. Statistical interpretation requires more than an outcome definition: it needs the observed estimate, its uncertainty, and enough information about the analysis to understand what population and comparison it represents.

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 limitations specific to this record constrain interpretation. First, numerical results for the primary and secondary outcomes are not reported in the registry record. There is therefore no reported estimate of mean change, variability, group contrast, or symptom-related correlation to evaluate.

Second, the endpoint description and timeframe are not fully aligned in wording. The timeframe specifies length at T= 20 minutes minus baseline at T=0, while the description specifies mean length with acid minus mean length with saline. The record does not explain how these comparisons were combined, what constituted the analyzed change, or the direction convention for the endpoint.

Third, the registry does not state random allocation and indicates the arms are not a like-for-like control comparison. Patients whose coronary artery disease was formally ruled out and healthy volunteers without esophageal symptoms are distinct populations. Any observed difference could reflect group characteristics as well as the physiological response under study; the record does not describe adjustment methods.

Fourth, participant flow, outcome-specific denominators, missing-data handling, analysis populations, and the statistical model are not reported in the registry record. The record also does not describe blinding, measurement reliability, protocol deviations, or procedures for ensuring comparable conditions. These omissions limit appraisal of bias and precision.

Finally, the registry lists no analysis results and does not report a multiplicity plan or interim-analysis approach. These are limits on what can be concluded from the registry record, not proof that the investigators did not address these issues elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Is Non-Cardiac Chest Pain Caused by Sustained Longitudinal Smooth Muscle Contraction? — NCT01839058.
• Registry record last updated 2018-11-26; status last verified 2018-11.
• Results first posted 2017-08-03.
• 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

NCT01839058 is a completed Queen’s University study with enrollment of 40 and a recorded start date of 2013-10 and primary completion date of 2014-10. It planned to evaluate esophageal shortening responses to acid in people with non-cardiac chest pain and healthy controls using esophageal manometry. The primary outcome is mean change in esophageal length with acid, measured in centimeters and summarized by a mean and standard deviation.

The registry lists three secondary outcomes related to esophageal length at symptom onset, length at maximal symptom intensity, and correlation between symptom onset and shortening. It records zero analyses and does not report numerical results for the outcomes. The available record therefore describes the research question and planned measurements but does not permit evaluation of the study’s observed effects, their precision, or whether the stated hypothesis was supported.