This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Musculoskeletal Effects of Bicarbonate (NCT01475214), a randomized phase 2 study. The primary outcome is The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01475214 |
| Phase | Phase 2 |
| Condition | Muscle Loss, Fractures, Osteoporosis, Age Related |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 244 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Tufts University |
| Results posted | Yes |
2. Clinical Question
Population
Healthy men and women age 60 years and older. The registry lists overall enrollment of 244. Its brief summary describes an intended study population of 138 men and 138 women; the registry does not explain how that description relates to the recorded enrollment.
Intervention
Potassium bicarbonate at a low dose of 1.0 mmol/kg per day or a higher dose of 1.5 mmol/kg per day. Each dose was described as being given in three even daily doses after meals with a full glass of water.
Comparator
An inactive placebo capsule described as microcrystalline cellulose. The registry identifies the trial as double blind but does not specify which trial roles were masked.
Primary question
How do changes in 24-hour urinary N-telopeptide (NTX) compare across placebo and the two potassium bicarbonate doses, and what dose is associated with maximal suppression of this measure at 84 days?
The clinical rationale in the registry is that mild, chronic metabolic acidosis may be relevant to age-related changes in bone and muscle. NTX is described as a marker of bone resorption. The trial therefore focused on whether the urinary measure changed across dose groups, rather than on fractures, falls, or clinical musculoskeletal outcomes as the primary endpoint.
The registry also describes urinary nitrogen excretion and selected measures of lower extremity performance as outcomes of interest, alongside safety and tolerability. However, it does not report numerical primary-outcome results or a single primary comparison. The primary outcome record is identified as having several categories or time points rather than a single comparison, so a numerical contrast between any two groups cannot be reconstructed from the registry information.
3. Trial Design
This was a Phase 2, randomized, double-blind, parallel-group dose-finding trial. It compared two potassium bicarbonate dose groups with an inactive placebo group. The registry lists Tufts University as the sponsor and the study status as completed. The recorded enrollment was 244. The start date is listed as 2012-01, and primary completion as 2014-12.
The registry describes the target population as healthy men and women aged 60 years and older. Its brief summary states an intended study of 138 men and 138 women, while its enrollment field records 244. The registry record does not explain this difference or provide the number enrolled in each arm. The listed conditions include muscle loss, fractures, age-related osteoporosis, and fall injury, but these condition labels do not establish that each was an eligibility criterion or a measured outcome.
Participants were assigned to low-dose potassium bicarbonate, higher-dose potassium bicarbonate, or placebo. The low dose was 1.0 mmol/kg per day and the higher dose was 1.5 mmol/kg per day, each divided into three even daily doses after meals with a full glass of water. The placebo was microcrystalline cellulose. The study summary describes evaluation over a 3-month period; the primary outcome timeframe is listed as 84 days.
Randomization helps create groups that are comparable, on average, with respect to both measured and unmeasured characteristics. Double masking is intended to reduce the influence of treatment knowledge on participant experience and outcome assessment, although the registry does not specify who was masked or how masking was maintained. A parallel design assigns participants to a group for comparison rather than describing a crossover. The registry does not report the randomization procedure, allocation concealment, detailed eligibility criteria, or participant flow through the trial.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Potassium Bicarbonate Low Dose | Potassium Bicarbonate Higher Dose | Inactive Capsule |
|---|---|---|---|
| STARTED | 84 | 79 | 81 |
| COMPLETED | 79 | 75 | 79 |
| NOT COMPLETED | 5 | 4 | 2 |
Reasons for not completing this period:
| Reason | Potassium Bicarbonate Low Dose | Potassium Bicarbonate Higher Dose | Inactive Capsule |
|---|---|---|---|
| Lost to Follow-up | 1 | 0 | 1 |
| Physician Decision | 2 | 0 | 0 |
| Withdrawal by Subject | 2 | 4 | 1 |
Analysis population for the primary outcome, as defined in the registry: Healthy men and women age 60 years and older
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.
| Characteristic | Unit | Potassium Bicarbonate Low Dose | Potassium Bicarbonate Higher Dose | Inactive Placebo Capsule | Total |
|---|---|---|---|---|---|
| Participants analysed | 84 | 79 | 81 | 244 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 40 | 40 | 41 | 121 |
| Age, Categorical: >=65 years | Participants | 44 | 39 | 40 | 123 |
| Age, Continuous | years | 67.4 (SD 5.5) | 66.4 (SD 5.1) | 66.8 (SD 6.1) | 66.9 (SD 5.6) |
| Sex: Female, Male: Female | Participants | 41 | 39 | 38 | 118 |
| Sex: Female, Male: Male | Participants | 43 | 40 | 43 | 126 |
| Race/Ethnicity, Customized: Caucasian, Non-hispanic | participants | 76 | 68 | 75 | 219 |
| Race/Ethnicity, Customized: Caucasian, Hispanic | participants | 2 | 1 | 2 | 5 |
| Race/Ethnicity, Customized: African-American | participants | 6 | 9 | 3 | 18 |
| Race/Ethnicity, Customized: Asian | participants | 0 | 1 | 1 | 2 |
| Region of Enrollment: United States | participants | 84 | 79 | 81 | 244 |
| Weight | kg | 74.8 (SD 13.7) | 74.2 (SD 13.0) | 73.2 (SD 14.0) | 74.1 (SD 13.6) |
| Glomerular Filtration Rate (GFR) | ml/min/1.73m^2 | 76.5 (SD 13.2) | 77.5 (SD 12.8) | 74.8 (SD 12.9) | 76.3 (SD 13.0) |
| Serum potassium | meq/L | 4.31 (SD 0.29) | 4.39 (SD 0.36) | 4.30 (SD 0.31) | 4.33 (SD 0.32) |
| Serum bicarbonate | mmol/L | 26.1 (SD 1.9) | 25.8 (SD 2.4) | 26.1 (SD 2.4) | 26.0 (SD 2.2) |
| Urine calcium/creatinine | mg/g | 99 (SD 43) | 99 (SD 48) | 114 (SD 69) | 104 (SD 55) |
6. Primary Endpoint
The registry lists the primary outcome as The Dose of Potassium Bicarbonate Needed for Maximal Suppression of 24-hr Urinary N-telopeptide, measured over 84 days.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Error |
| Unit | nmol/day |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the dose of potassium bicarbonate needed for maximal suppression of 24-hour urinary N-telopeptide (NTX). The registry describes the measured outcome as changes in urinary NTX compared across placebo and the potassium bicarbonate doses. Its unit is nmol/day, its summary parameter is the mean, and its dispersion measure is the standard error. The stated timeframe is 84 days.
NTX is described in the registry as a marker of bone resorption. Urinary measurement offers a way to quantify a biological process relevant to bone turnover during an intervention. A dose-finding study can compare multiple doses to explore whether the measured response varies with dose and which dose is associated with the greatest change in the chosen marker. Such a marker is not itself a fracture, a fall, or a direct measure of overall musculoskeletal health.
General statistical context: a mean summarizes the average observed measure in a group, while a standard error describes the precision of an estimated mean. A smaller standard error generally indicates a more precise estimate, but interpretation also depends on the scale of the outcome and the analysis. The registry does not report the numerical group means, standard errors, baseline values, changes, or between-group estimates for NTX. It therefore does not allow readers to judge the size or precision of the primary outcome response.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes the question, design, intervention groups, and primary endpoint, but it does not provide numerical findings for the primary NTX outcome. It describes comparison of changes across placebo and two potassium bicarbonate doses, yet the primary outcome is not reduced to one comparison because it has several categories or time points. No numeric contrast, uncertainty interval, or p-value for NTX is reported in the registry record. As a result, the direction, magnitude, and precision of the primary outcome differences cannot be interpreted from the registry information.
The endpoint is a continuous measure summarized as a mean, with standard error identified as the dispersion measure. To understand a dose-finding result, readers would ordinarily need to see the outcome values by group and time, as well as an estimate of the relevant between-group differences and their uncertainty. Those details are not reported in the registry record. The stated primary aim of identifying a dose associated with maximal suppression should therefore be read as the research question, not as a finding that the registry establishes.
The record does not report outcomes for urinary nitrogen or lower extremity performance, although the brief summary describes them as measures to be evaluated. Nor does the record provide numerical results for safety and tolerability beyond the adverse-event counts and terms listed separately. In particular, the listed adverse-event information does not supply an analysis relating adverse events to changes in NTX or to the intended biological response.
General statistical context: a confidence interval expresses a range of values compatible with the data and model under stated assumptions. It helps distinguish a precise estimate from one that remains uncertain. A p-value, when reported, addresses compatibility with a specified null model; it does not measure clinical importance or establish the probability that a treatment effect is true. Neither can substitute for the estimate itself. Because the registry lacks the primary numerical estimates and their uncertainty, no conclusion about statistical evidence or response size can be drawn from this record alone.
The trial's randomized, double-blind design is relevant to how a complete analysis might be interpreted, but design features do not fill gaps in the posted results. The record does not establish whether observed group differences occurred, whether they differed by dose, or how consistently participants' responses varied. It also does not establish effects on clinical events such as fractures or falls. Any broader claim about musculoskeletal benefit would go beyond the numerical information reported in the registry.
9. Statistical Methods Explained
What does a randomized parallel-group design contribute?
Random assignment is intended to make the treatment groups comparable at the start of a trial, apart from chance imbalances. This supports a fair comparison of outcomes between the potassium bicarbonate doses and placebo. In a parallel-group design, participants are assigned to one group for the study comparisons. The registry identifies the study as randomized and parallel, but does not describe the sequence-generation method, allocation concealment, stratification, or how randomization was implemented.
Double masking is intended to limit bias that could arise if knowledge of group assignment influences reporting, care, or outcome assessment. The registry labels the study double blind, but does not say whether participants, investigators, outcome assessors, or other staff were masked. The registry also does not describe procedures for maintaining or checking masking. Those operational details are not reported in the registry record.
What does the mean and standard error describe?
NTX is a continuous outcome measured in nmol/day. The registry identifies the mean as the summary parameter and the standard error as its dispersion measure. The mean represents the average outcome in the group or analysis being described. The standard error reflects uncertainty in an estimated mean, rather than the spread of individual participant values. General statistical context: variability among individuals and uncertainty in an estimated group mean are different quantities. A standard deviation is commonly used to describe individual-level spread; a standard error is commonly used to describe the precision of an estimate.
For a comparison of two groups, the clinically and statistically relevant quantity is often the estimated difference between groups, with an uncertainty measure such as a confidence interval. The registry does not report such a difference for NTX. It also does not give the actual group means, standard errors, or details of the model used to estimate changes. The mean and standard error labels describe how the outcome was intended to be summarized, not the missing numerical result.
Why does dose-finding require more than a single group comparison?
The study question concerns two active doses and a placebo, with an aim of identifying a dose associated with maximal suppression of urinary NTX. Comparing each dose with placebo can answer whether each dose differs from the comparator under a specified analysis. Comparing the doses with one another can address whether the dose levels are associated with different responses. A dose-response pattern may also be assessed using an appropriate model, but the registry does not report whether such a model was planned or used.
When several doses, outcomes, or time points are examined, the interpretation depends on which comparisons were planned and how multiplicity was handled. The registry describes multiple categories or time points for the primary outcome and does not reduce them to one comparison. It does not report the specific contrast definitions or a statistical analysis plan. It is therefore not possible to identify a single primary estimate or determine how the different comparisons were treated statistically.
What can be inferred from planning illustrations?
The registry describes sample-size illustrations based on the observed effect. Their assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning illustrations, not evidence about the effect observed in the trial and not observed power. The registry does not report the trial's own sample-size justification or the numerical illustration results in the registry record for interpretation.
General statistical context: a sample-size calculation is conditional on assumptions about the outcome variability, target effect, significance level, and allocation. Changing those assumptions can change the estimated number of participants needed. An illustration based on an observed effect describes a hypothetical planning scenario; it does not show the probability that the completed trial detected an effect. Because the primary outcome estimate is not reported, these illustrations cannot be used to infer the trial's result.
Why do missing analysis details matter?
The registry lists no analysis entries. It does not report whether the primary comparison used an intention-to-treat, per-protocol, or other analysis population; how missing outcome measurements were handled; whether covariates or baseline values were included; or what model was used for repeated measurements. These choices can affect estimates and their uncertainty. General statistical context: repeated measurements on the same participant are usually correlated, so an analysis may need to account for that within-participant dependence. The record does not say whether or how this was done.
These omissions do not prove that no analysis occurred; they mean that the registry record does not describe one. Without the analysis population, missing-data procedures, and outcome estimates, readers cannot reproduce the primary comparison or evaluate how sensitive it may be to analysis choices. Any interpretation of the outcome must remain limited to what the registry actually reports.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is described as having several categories or time points and is not reduced to a single comparison. The registry does not identify a hierarchy of comparisons, specify which time point would serve as the main inferential test, or report a multiplicity adjustment. It also does not report whether other outcomes—such as urinary nitrogen or lower extremity performance—were included in a broader testing strategy. With several possible comparisons, the risk of chance findings can increase if analyses are interpreted without accounting for how many were examined. The registry record does not describe how this issue was handled.
Missing-data methods are not reported in the registry record. There is no account of the amount or pattern of missing NTX measurements, withdrawals by group, imputation, or sensitivity analyses. The record also does not describe whether participants with incomplete measurements were included in any particular analysis. These omissions make it difficult to assess whether the available outcome data represent all randomized participants or whether missingness could influence the estimates.
The analysis populations are not reported in the registry record. In particular, there is no description of an intention-to-treat population, a per-protocol population, or other inclusion rules for outcome analyses. No statistical analysis entries are listed, and the record does not specify covariate adjustment, repeated-measures methods, or handling of protocol deviations. These details matter because different analysis choices can lead to different estimates and uncertainty. The absence of this information is a reporting limitation, not evidence that a particular method was or was not used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Potassium Bicarbonate Low Dose | 3 | 84 | 3.6% |
| Potassium Bicarbonate Higher Dose | 3 | 79 | 3.8% |
| Inactive Capsule | 1 | 81 | 1.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Potassium Bicarbonate Low Dose | 19 of 84 |
| Potassium Bicarbonate Higher Dose | 29 of 79 |
| Inactive Capsule | 23 of 81 |
Most frequent serious adverse event terms
| Event term | Organ system | Potassium Bicarbonate Low Dose | Potassium Bicarbonate Higher Dose | Inactive Capsule |
|---|---|---|---|---|
| Contusions/abrasions | Musculoskeletal and connective tissue disorders | 1 of 84 | 1 of 79 | 0 of 81 |
| High serum potassium | Renal and urinary disorders | 0 of 84 | 1 of 79 | 0 of 81 |
| GI upset | Gastrointestinal disorders | 1 of 84 | 0 of 79 | 0 of 81 |
| Abdominal aortic repair | Cardiac disorders | 0 of 84 | 0 of 79 | 1 of 81 |
| Fracture | Musculoskeletal and connective tissue disorders | 0 of 84 | 1 of 79 | 0 of 81 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 84 | 0 of 79 | 0 of 81 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Potassium Bicarbonate Low Dose | Potassium Bicarbonate Higher Dose | Inactive Capsule |
|---|---|---|---|---|
| GI upset | Gastrointestinal disorders | 5 of 84 | 9 of 79 | 6 of 81 |
| High serum potassium | Renal and urinary disorders | 5 of 84 | 8 of 79 | 5 of 81 |
| low GFR | Renal and urinary disorders | 4 of 84 | 3 of 79 | 3 of 81 |
| Headache | General disorders | 1 of 84 | 1 of 79 | 2 of 81 |
| dizziness | General disorders | 1 of 84 | 2 of 79 | 0 of 81 |
| Knee/hip injury | Musculoskeletal and connective tissue disorders | 1 of 84 | 2 of 79 | 0 of 81 |
| Sprain | Musculoskeletal and connective tissue disorders | 0 of 84 | 0 of 79 | 3 of 81 |
| Constipation/diarrhea | Gastrointestinal disorders | 1 of 84 | 1 of 79 | 1 of 81 |
| Heart palpitations | Cardiac disorders | 0 of 84 | 1 of 79 | 1 of 81 |
| Fever, fatigue | General disorders | 0 of 84 | 0 of 79 | 1 of 81 |
Serious events with the highest arm-level rate: high serum potassium (1.3%), contusions/abrasions (1.3%), fracture (1.3%), abdominal aortic repair (1.2%), gi upset (1.2%).
The registry lists serious adverse-event counts by group: 3 affected among 84 at risk in the low-dose group, 3 among 79 in the higher-dose group, and 1 among 81 in the inactive-capsule group. It also lists other adverse events: 19 among 84 at risk in the low-dose group, 29 among 79 in the higher-dose group, and 23 among 81 in the inactive-capsule group. These are group-level counts as recorded; the registry does not provide a statistical comparison or an assessment of whether events were caused by the intervention.
The listed serious-event terms include high serum potassium, contusions/abrasions, fracture, abdominal aortic repair, GI upset, and pneumonia, with percentages reported as 1.3%, 1.3%, 1.3%, 1.2%, 1.2%, and 1.2%, respectively. The record does not assign these terms to specific treatment groups in the information, so they should not be interpreted as group-specific rates. Death counts are not reported in the registry record; a missing death value should not be read as zero.
General statistical context: adverse-event counts describe what was recorded during the study, but small group counts can be imprecise and do not by themselves establish a difference in risk. Interpretation also depends on event definitions, follow-up, severity, timing, and attribution procedures. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record identifies a completed randomized dose-finding trial in older adults and specifies a primary biological outcome: change in 24-hour urinary NTX across placebo and two potassium bicarbonate doses. It also provides the intervention schedules, overall enrollment, and some adverse-event counts. These registry entries describe the trial's question and design, but they do not supply the numerical primary outcome results.
Accordingly, the registry record does not establish which dose, if any, was associated with greater NTX suppression, how large any differences were, or how precisely they were estimated. It also does not establish whether the outcome differences were statistically distinguishable from chance under a particular analysis. The primary outcome is described across several categories or time points rather than as a single comparison, and no analysis entries are listed.
General statistical context: NTX is a marker of bone resorption, not a direct measure of fractures, falls, physical function, or overall health. A change in a biological marker may be useful for studying a mechanism, but it cannot by itself establish a change in a clinical outcome. The registry also does not report the numerical results for the other measures described in the study summary, including urinary nitrogen and lower extremity performance.
The adverse-event counts can be described as recorded events in the three groups, but they do not establish that an event was caused by potassium bicarbonate or that groups differ in safety. The record does not report an inferential safety comparison, and death values are not reported. Conclusions about efficacy, clinical benefit, or comparative safety would require results and analysis details beyond those in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for addressing a dose-finding question rather than only a two-group comparison. It includes two potassium bicarbonate doses and a placebo, with urinary NTX identified as the primary measure. That structure can support questions about whether responses differ across doses, but a clear interpretation depends on the selected comparisons, outcome time points, and analysis model. Those details and the numerical results are not reported in the registry record.
The registry distinguishes a biological marker from clinical outcomes by specifying urinary NTX as the primary endpoint while also describing urinary nitrogen and lower extremity performance as additional measures. This distinction is important in statistical interpretation: an estimate for a marker answers a narrower question than an estimate for fractures, falls, or functional outcomes. The record does not provide numerical findings for those additional measures either.
The sample-size assumptions are described as planning illustrations based on the observed effect, not as the trial's own design justification. That distinction matters because a planning scenario is not a post hoc measure of whether the trial had sufficient power, and it does not substitute for the estimated effect and its uncertainty. The registry does not report the trial's sample-size justification or analysis entries.
Finally, the record demonstrates why trial design information and outcome reporting should be read separately. Randomization, masking, dose schedules, and enrollment identify how a study was structured; they do not reveal what the primary analysis found. Without the primary estimates, uncertainty measures, analysis population, and missing-data procedures, statistical conclusions remain limited even when the research question and design are clearly stated.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most important trial-specific limitation for interpreting the registry is the absence of numerical primary-outcome results. The record states that the endpoint concerns change in urinary NTX across three groups at 84 days, but does not report group means, standard errors, changes, or between-group estimates. It identifies several categories or time points and does not reduce them to one comparison. Consequently, neither the magnitude nor precision of the primary response can be assessed.
The registry does not report the detailed statistical analysis plan, analysis populations, handling of missing data, participant flow by group, or whether baseline adjustment was used. It does not explain how multiple comparisons across doses, categories, or time points were handled. These omissions limit assessment of the analysis and make it impossible to reproduce a primary comparison from the registry record.
The summary describes an intended population of 138 men and 138 women, while the enrollment field records 244. The registry does not explain the relation between these figures or give enrollment by group or sex. Eligibility details beyond healthy men and women aged 60 years and older are not reported in the registry record. Generalizability beyond this described population therefore cannot be judged from the available details.
The study's primary endpoint is a urinary marker rather than a clinical event, and the registry does not report numerical results for the additional measures described in the summary. Adverse-event counts are listed, but group-specific serious-event terms, attribution, timing, and comparative analyses are not reported. These limitations constrain interpretation of both benefit-related outcomes and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Musculoskeletal Effects of Bicarbonate — NCT01475214.
- Registry record last updated 2015-10-19; status last verified 2015-09.
- Results first posted 2015-10-19.
- 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.
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18. Record Summary
NCT01475214 is a completed Phase 2 randomized, double-blind, parallel-group dose-finding trial sponsored by Tufts University. It recorded enrollment of 244 and compared potassium bicarbonate at 1.0 mmol/kg per day and 1.5 mmol/kg per day with an inactive placebo capsule. The target population was healthy men and women age 60 years and older.
The primary endpoint was 24-hour urinary NTX, measured in nmol/day, with the mean and standard error specified and a timeframe of 84 days. The registry does not report numerical results for this endpoint or analysis entries. It lists serious and other adverse-event counts by group but does not report deaths or an inferential safety comparison.