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 Uridine Adolescent Bipolar Depression Randomized Controlled Trial (NCT01805440), a randomized na study. The primary outcome is Change in GLX (Glutamate + Glutamine) to Creatine (Cr) Ratio in the Anterior Cingulate Cortex of the Brain, as Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01805440 |
| Phase | NA |
| Condition | Bipolar Disorder, Bipolar Depression, Manic Depression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 62 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns adolescents with bipolar depression associated with bipolar disorder. The registry record describes depressed adolescents with bipolar disorder as the intended participants, but detailed eligibility criteria and the characteristics of those enrolled are not reported in the registry record. The record lists an enrollment of 62. It also identifies a Healthy Comparison group whose participants were not randomized and received no treatment intervention; that group is distinct from the randomized treatment comparison.
Intervention
Participants assigned to uridine were to take 500 mg by mouth twice daily for 6 weeks. Uridine is described as an investigational drug in the study summary. After completing the 6-week protocol, participants were to be offered 6 months of open-label uridine treatment and follow-up, whether their initial assignment was uridine or placebo. The registry record does not report how many participants accepted or completed that later offer.
Comparator
The randomized comparator was placebo, given at 500 mg by mouth twice daily for 6 weeks. This allows the initial study period to compare the uridine assignment with a placebo assignment. The healthy comparison participants were not randomized and did not receive an intervention, so they should not be treated as a third randomized treatment arm.
Primary question
The primary endpoint concerns change from baseline to 6 weeks in the GLX (glutamate plus glutamine) to creatine ratio in the anterior cingulate cortex, measured with proton-1 magnetic resonance spectroscopy (1H-MRS). The clinical question is whether the posted measurements describe a difference in this brain-chemistry measure between the randomized uridine and placebo groups. The registry record does not report a result for that comparison, so it does not establish the direction, size, or precision of any treatment-group difference.
3. Trial Design
This is a randomized, parallel-group study comparing uridine with placebo over a 6-week protocol. The registry lists allocation as randomized and masking as quadruple. Its brief summary describes the study as double-blind. The record does not explain the difference between those masking descriptions or specify which study roles were masked.
The planned treatment was uridine 500 mg twice daily by mouth or matching placebo at the same stated dose and frequency. The total enrollment is listed as 62. The number assigned to each randomized group, the allocation ratio, and the method used to generate or conceal the assignment are not reported in the registry record. A Healthy Comparison group is also described, but its participants were not randomized and received no treatment intervention.
After the initial protocol, participants completing the 6-week period were to be offered 6 months of open-label uridine treatment and follow-up. The registry summary says this offer applied to participants initially assigned to either randomized group. This later phase is open-label and should be distinguished from the initial placebo-controlled comparison. Whether participants entered, completed, or contributed data to that phase is not reported in the registry record.
The study is listed as completed. Its start is recorded as 2013-08 and its primary completion as 2015-12. The record identifies University of Utah as the sponsor and lists the phase as NA. These design details describe the study structure; they do not provide evidence about the primary endpoint’s result.
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 | Uridine | Placebo | Healthy Comparison |
|---|---|---|---|
| STARTED | 19 | 17 | 26 |
| COMPLETED | 18 | 17 | 26 |
| NOT COMPLETED | 1 | 0 | 0 |
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 | Uridine | Placebo | Healthy Comparison | Total |
|---|---|---|---|---|---|
| Participants analysed | 19 | 17 | 26 | 62 | |
| Age, Categorical: <=18 years | Participants | 10 | 6 | 6 | 22 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 11 | 20 | 40 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 16.74 (SD 2.28) | 18.29 (SD 2.62) | 18.54 (SD 2.37) | 17.47 (SD 2.54) |
| Sex: Female, Male: Female | Participants | 14 | 10 | 16 | 40 |
| Sex: Female, Male: Male | Participants | 5 | 7 | 10 | 22 |
| Region of Enrollment: United States | participants | 19 | 17 | 26 | 62 |
6. Primary Endpoint
The registry lists the primary outcome as Change in GLX (Glutamate + Glutamine) to Creatine (Cr) Ratio in the Anterior Cingulate Cortex of the Brain, as Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS)., measured over Baseline and 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Brain GLX/Cr |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change in the GLX to creatine ratio in the anterior cingulate cortex between baseline and 6 weeks. GLX combines glutamate and glutamine, and the measure is expressed as a brain GLX/Cr ratio. The registry specifies a mean continuous measure with standard deviation as the dispersion description. The measurement method is proton-1 magnetic resonance spectroscopy (1H-MRS).
As a general explanation, magnetic resonance spectroscopy estimates concentrations of selected brain chemicals without an invasive sampling procedure. A ratio to creatine expresses the target measurement relative to another brain metabolite, rather than as an isolated concentration. The registry rationale says GLX is of interest because prior research indicates elevated Glx concentrations among adolescents with bipolar depression compared with controls. It presents the measure as a potential biomarker related to disease mechanisms and treatment response, not as a direct measure of symptoms or daily functioning.
Interpreting a change endpoint requires information about the group-level measurements and the comparison between groups. The registry record gives the measurement, timing, and rationale, but does not report the primary outcome result or an analysis estimate. Therefore, the size and precision of any difference in change cannot be described from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of uridine and placebo and identifies change in the anterior cingulate cortex GLX/Cr ratio from baseline to 6 weeks as the primary endpoint. However, it lists 0 analyses and gives no numerical result for that endpoint. The record therefore does not support a statement about the estimated difference between treatment groups, its direction, or its precision. It also does not report a confidence interval or a statistical test for the primary comparison.
The record lists 3 outcome measures and names the Columbia-Suicide Severity Rating Scale (C-SSRS) as a secondary outcome. It does not give results for that secondary measure. Without outcome estimates, it is not possible to describe whether measurements changed within either group, whether changes differed between groups, or whether any observed difference was compatible with a broad range of effects.
The enrollment of 62 describes the study’s overall enrollment, not the number included in a particular outcome analysis. Group-specific primary-outcome sample sizes, missing measurements, exclusions, and analysis populations are not reported in the registry record. Those details matter because the amount and pattern of available outcome data affect both the estimate and its uncertainty. The record also does not state whether the analysis adjusted for baseline values or used another approach to model repeated measurements.
The adverse-event figures are descriptive safety counts, not evidence about the primary brain spectroscopy endpoint. The record lists serious adverse events for the uridine and placebo groups and also reports participants affected by other adverse events. These counts should be read with their listed group denominators and without assuming that they establish causation. The record does not provide enough detail to connect an individual event to treatment exposure, timing, or clinical course.
Any sample-size calculations associated with the posted material are planning illustrations based on the observed effect and stated assumptions, not observed power. They do not replace a reported treatment-effect estimate or its uncertainty. The registry’s missing primary analysis is the central interpretive limitation: the design and endpoint can be described, but the comparative efficacy result cannot be reconstructed from the record.
9. Statistical Methods Explained
What does a continuous endpoint mean?
The primary measure is continuous: each participant’s GLX/Cr ratio can take a range of values rather than being assigned to a yes-or-no category. A mean describes the central value across observations, while a standard deviation describes how dispersed those observations are around the mean. These summaries alone would not show the uncertainty in a treatment-group comparison. A confidence interval, when reported, would describe the range of values reasonably compatible with the analysis under its assumptions. No primary estimate or confidence interval is reported in the registry record.
Why compare change between randomized groups?
For a baseline-to-follow-up endpoint, the scientific comparison is generally about how measurements change in the treatment groups relative to one another, rather than whether one group changed on its own. A change within a group can reflect many influences, including time, measurement variation, and treatment. Random assignment is intended to make groups comparable on average, but the registry record does not report the actual group-level baseline values or the analysis used to compare change. Thus, the planned randomized design can be described, while the result of that comparison cannot.
What does masking contribute?
Masking is intended to limit influences on participant experience, study conduct, and outcome assessment. The registry lists quadruple masking, while the study summary uses the description double-blind. The record does not reconcile these terms or specify the roles kept unaware of assignment. It also does not report whether masking was assessed or maintained throughout the initial treatment period. The presence of a masking designation describes an intended design feature, not proof that masking was successful.
Why does uncertainty matter?
An estimate describes the observed contrast under a chosen analysis; its uncertainty describes how much the estimate might vary because only a sample of participants was observed. A confidence interval is one common way to communicate that uncertainty. A narrow interval would generally indicate greater precision than a wide interval, but interpretation also depends on the endpoint, design, and analysis. Since the primary outcome estimate and interval are not reported in the registry record, neither the size nor the precision of the treatment contrast can be assessed.
How should planning calculations be read?
As a general statistical concept, power calculations describe the chance that a planned analysis will detect a specified effect under stated assumptions. They are design tools, not evidence that an effect occurred. The sample-size illustrations associated with the posted material are based on the observed effect, use a two-sided significance level of 0.05, assume equal allocation between the two arms, and use a normal approximation. They are planning illustrations, not observed power. The record does not report the trial’s own sample-size justification or enough detail to identify its original planning assumptions.
The effect used in a planning illustration is an assumption for the calculation. If it is derived from an observed estimate, its uncertainty and possible instability matter; the illustration should not be taken as confirmation that the same effect is present in a broader population. The registry record does not provide the primary estimate needed to independently assess that basis.
What can the listed analysis count tell readers?
The record lists 0 analyses. This means there is no posted inferential analysis in the registry record to interpret for the primary endpoint. It does not, by itself, explain whether analyses were conducted elsewhere, whether results were unavailable, or why no analysis is listed. The statistical model, handling of baseline measurements, assumptions about missing data, and any adjustments are not reported in the registry record. Without these details and the outcome estimates, a reader cannot judge model fit or reproduce the primary comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures, identifies the GLX/Cr change as primary, and names the C-SSRS as a secondary outcome. It does not report how many hypotheses were tested, whether outcomes were tested in a prespecified order, or whether any adjustment for multiple comparisons was planned. Multiplicity matters in general because considering several outcomes or analyses can increase the chance that at least one appears noteworthy by chance. The record does not provide enough information to evaluate that issue for this study.
Missing-data methods and outcome-analysis populations are not reported in the registry record. The total enrollment of 62 does not establish how many participants had baseline and 6-week spectroscopy measurements, how many were included in the primary analysis, or how missing values were handled. The record does not state whether the analysis followed randomized assignment regardless of treatment received, used only participants with complete measurements, or applied another population definition. Those choices can affect the estimate and its uncertainty.
The study summary describes a later open-label offer of uridine and follow-up after the initial 6-week protocol. It does not report how the later period was analyzed or whether those data were included in any outcome analysis. Because the primary comparison is not reported and the analysis count is 0, the registry record does not permit an assessment of multiplicity handling, missing-data assumptions, or consistency between planned and reported analyses.
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 |
|---|---|---|---|
| Uridine | 1 | 19 | 5.3% |
| Placebo | 0 | 17 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Uridine | 0 of 19 |
| Placebo | 0 of 17 |
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 |
|---|---|
| Uridine | 12 of 19 |
| Placebo | 5 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | Uridine | Placebo |
|---|---|---|---|
| Other Serious (Important Medical Event) | Psychiatric disorders | 1 of 19 | 0 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Uridine | Placebo |
|---|---|---|---|
| Stomach Discomfort | Gastrointestinal disorders | 8 of 19 | 3 of 17 |
| Nausea | Gastrointestinal disorders | 5 of 19 | 3 of 17 |
Serious events with the highest arm-level rate: other serious (important medical event) (5.3%).
The registry lists serious adverse events among participants at risk in the uridine and placebo groups. In the uridine group, 1 of 19 participants at risk was affected by a serious adverse event; in the placebo group, 0 of 17 were affected. It reports 0 deaths in each group. The most frequently listed serious-event term is “Other Serious (Important Medical Event),” reported as 5.3%.
The record also lists other adverse events affecting 12 of 19 participants at risk in the uridine group and 5 of 17 in the placebo group. These are descriptive counts. They do not establish that an event was caused by the assigned intervention, and they do not describe its severity, duration, recurrence, or clinical course. The registry record does not report the event-level detail needed to interpret those features.
The group denominators listed for safety are not necessarily the same as the total enrollment or the participants with primary endpoint measurements. Small counts can be imprecise, and the registry does not provide a comparative safety analysis or uncertainty estimates. The figures therefore describe what the record reports, rather than establishing a causal difference between groups.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, parallel-group study compared a 6-week course of uridine with placebo in adolescents with bipolar depression. It specifies a primary brain spectroscopy measure, a baseline and 6-week timeframe, and a rationale for examining GLX relative to creatine in the anterior cingulate cortex. These features identify the question the trial was designed to address.
It does not establish what the randomized comparison found. No primary endpoint estimate, confidence interval, or analysis is reported in the registry record, and the record lists 0 analyses. Consequently, the available information cannot show whether the GLX/Cr ratio changed, how much it changed, or whether change differed between the randomized groups. The C-SSRS is listed as a secondary outcome, but its results are not reported either.
The safety counts are separate from the efficacy question. They provide event counts for the listed groups but do not, on their own, establish that treatment caused or prevented events. They also do not supply a full account of adverse-event timing, clinical seriousness, or follow-up.
The proposed open-label period is distinct from the initial placebo-controlled phase. An offer of later treatment and follow-up is not itself evidence about participation or outcomes during that period. The registry record does not report whether participants entered that phase or what its findings were.
Overall, the record supports a description of the trial’s design, endpoint, and selected safety counts, but not a conclusion about the size, direction, or clinical meaning of the primary treatment effect. A biomarker measurement is not interchangeable with a direct assessment of symptoms or functioning; the registry’s stated primary endpoint is the spectroscopy ratio.
13. Why This Trial Matters Statistically
This study is statistically notable for using a continuous imaging-based biomarker as its primary endpoint in a randomized placebo-controlled design. That design places the focus on a between-group comparison over the initial treatment period, while the endpoint description identifies a specific brain region, metabolite ratio, measurement method, and follow-up time. Making those elements explicit helps readers distinguish the biological measurement from clinical outcomes.
The record also illustrates why a registered design and a reported analysis serve different purposes. Randomization and masking describe how a study was intended to reduce bias. They do not reveal the observed treatment contrast, its precision, or the robustness of the analysis. Here, the record lists no analyses and gives no primary estimate, so the design cannot be used as a substitute for outcome reporting.
The distinction between the randomized groups and the untreated Healthy Comparison group is important. The healthy group may provide a descriptive reference, but it was not randomized and did not receive an intervention. It therefore does not replace the placebo group as the comparator for the randomized treatment question.
Finally, the record includes a planned open-label extension and selected safety counts. Separating these from the controlled period helps prevent different designs and kinds of evidence from being conflated. For statistical interpretation, transparent outcome estimates, uncertainty, analysis populations, and missing-data methods are necessary to judge what the trial can support. Those details are not reported in the registry record.
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 primary limitation is the absence of a reported primary-outcome analysis. The registry lists 0 analyses, so no treatment-group estimate, uncertainty interval, or test is available for the GLX/Cr endpoint. The record also does not report group-specific baseline or follow-up values, preventing readers from examining the measurements underlying the intended comparison.
Several design and analysis details are not reported in the registry record: eligibility criteria, randomized group sizes, allocation ratio, assignment procedures, primary analysis population, model specification, handling of missing measurements, and multiplicity procedures. The listed total enrollment of 62 cannot answer how many participants contributed to the endpoint analysis. The registry’s quadruple-masking designation and the summary’s double-blind wording are not reconciled.
The endpoint is a brain spectroscopy ratio, not a direct symptom or functioning measure. The record gives a biological rationale but no primary result or evidence linking any measured change to a clinical outcome in this trial. The C-SSRS is listed as a secondary outcome without results. Details of the planned open-label period, including uptake and follow-up findings, are also absent.
Safety information is limited to group counts and a serious-event term. Event descriptions, timing, attribution, and uncertainty are not reported. These limitations mean the record supports a study-design description and a narrow account of listed safety counts, but not a complete evaluation of outcome effects or harms.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Uridine Adolescent Bipolar Depression Randomized Controlled Trial — NCT01805440.
- Registry record last updated 2018-03-12; status last verified 2018-03.
- Results first posted 2018-03-12.
- 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
The record describes a completed randomized, parallel-group, placebo-controlled study sponsored by University of Utah. Enrollment is listed as 62, with a start in 2013-08 and primary completion in 2015-12. The initial treatment period was 6 weeks, with uridine or placebo taken 500 mg twice daily by mouth. Participants were to be offered 6 months of open-label uridine treatment and follow-up after completing the initial protocol.
The primary endpoint was change from baseline to 6 weeks in the anterior cingulate cortex GLX/Cr ratio measured by 1H-MRS. The record lists the C-SSRS as a secondary outcome, 3 outcome measures, and 0 analyses. It therefore does not report a primary efficacy estimate or secondary outcome results. Safety listings include serious and other adverse-event counts for the uridine and placebo groups, plus 0 deaths in each group.