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 I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers (NCT02323217), a na early/phase 1 study. The primary outcome is Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02323217 |
| Phase | EARLY/Phase 1 |
| Condition | Healthy Volunteers, Alzheimer Disease, Molecular Imaging |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers. The record lists an enrollment of 20, but does not report detailed eligibility criteria or participant characteristics.
Intervention
The study lists [11C]BU99008, Idazoxan, and Isocarboxazid. Their specific roles, timing, and use in relation to the imaging assessments are not reported in the registry record.
Comparator
No separate comparator group is described. The study is listed as a single-group study with allocation recorded as NA and no masking.
Primary question
How are imidazoline2 binding sites distributed regionally in the brains of healthy volunteers, as measured using PET-derived parameters such as total volume of distribution or binding potential?
The registry frames the main objective as quantifying and locating imidazoline2 binding sites (I2BS) in the healthy human brain. These sites are described in the background as residing inside astrocytes, and the record gives a scientific rationale for studying their distribution with an imaging method. The stated primary outcome is regional density and distribution, with an outcome expressed as a mean and standard deviation in mL/cm^3 over a timeframe of 1 week.
This is a measurement study, not a randomized comparison of treatments. The registry does not describe a healthy control arm separate from the participants who underwent the imaging assessments, nor does it provide a treatment-effect question. The listed drug interventions do not establish what comparisons, if any, were planned or performed. Their roles are not reported in the registry record.
The primary question is therefore descriptive: what regional PET-derived values characterize I2BS in the studied healthy volunteers? The registry record does not report the resulting regional values, so it does not establish the magnitude or precision of those measurements. It also does not report a comparison with people who have Alzheimer disease or another condition. Although Alzheimer disease appears among the listed conditions and is discussed in the background, the described primary population is healthy volunteers.
3. Trial Design
NCT02323217 is listed as an early-phase 1, single-group study with an enrollment of 20. Its status is completed. The registry gives a start date of 2015-01 and a primary completion date of 2016-02. Imperial College London is listed as the sponsor. No randomized allocation is described: allocation is recorded as NA. Masking is recorded as none.
The study is titled I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers. Its official title describes quantification and localisation of I2BS in healthy volunteers using [11C]BU99008 in a positron emission tomography study. The primary outcome description identifies regional density and distribution in the healthy human brain as the aim. It names total volume of distribution (VT) or binding potential (BP) as possible output parameters, depending on the PET pharmacokinetic model considered most appropriate for the ligand.
The record lists [11C]BU99008 as a radiation intervention, and Idazoxan and Isocarboxazid as drug interventions. It does not report the administration schedule, dose, order of procedures, or the role of each intervention in the study. The single-group designation does not establish whether the same participants received every listed intervention or which measurements were associated with each one.
There is no like-for-like control comparison described. The study should therefore be read as a non-randomized imaging investigation rather than as a trial estimating a between-group treatment effect. The arm description names Healthy Volunteers but gives no further detail. Participant demographics, recruitment procedures, eligibility criteria, and the number who completed each imaging or drug procedure are not reported in the registry record.
The registry lists five outcome measures and zero analyses. Those entries do not provide outcome values or analysis results. The design description also does not report a protocol-level sample-size justification, a planned analysis population, or details of any interim analyses. Such information cannot be inferred from the enrollment target or from the fact that the study is marked completed.
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 | Healthy Volunteers |
|---|---|
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 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 | Healthy Volunteers |
|---|---|---|
| Participants analysed | 18 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 18 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model), measured over 1 week.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mL/cm^3 |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled “Determination of the Regional Density and Distribution of I2BS in Healthy Human Brain (1TCM Model).” It is a continuous measure reported as a mean with standard deviation, with units of mL/cm^3 and a timeframe of 1 week. The description says that the output would be derived from the PET pharmacokinetic model considered most appropriate for the ligand. VT, the regional distribution volume, and BP, binding potential, are named as possible parameters.
These quantities are used in PET kinetic analysis to characterize radiotracer distribution in tissue. In general, a regional measure allows researchers to describe how a tracer-derived signal varies across brain regions, while a pharmacokinetic model relates the measured time course to tracer movement and retention. A model-based measure can be useful when the raw signal alone does not answer the study’s biological question. The record does not identify a final selected parameter or provide regional endpoint values.
The methods description states that regional time-activity data were generated from arterial plasma input functions corrected for metabolites. It says that kinetic analyses were performed in MIAKAT, and that Akaike model selection criteria were used to determine which of three stated approaches best described the data: a one-tissue compartmental model (1TCM), a two-tissue compartmental model (2TCM), or a multilinear analysis model (MA). The endpoint title names 1TCM, but the record does not report the model-selection results or the resulting regional estimates.
Consequently, the endpoint definition explains what the study intended to measure, not what values it found. Neither the primary outcome means nor their standard deviations are reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a PET study intended to quantify regional I2BS in healthy volunteers. Its primary outcome is continuous and is to be expressed as a mean with standard deviation in mL/cm^3. However, the record does not report any primary outcome values, regional estimates, or statistical analyses. It is therefore not possible to describe the size, variability, or precision of the measured regional values from this record.
The enrollment is listed as 20, while the adverse-event record lists 18 participants at risk for each of its event categories. These are distinct registry entries and should not be treated as interchangeable counts. The record does not explain the difference or state how many participants contributed data to the primary endpoint. It does not report the number analyzed for each region, the handling of incomplete scans, or whether any enrolled participants were excluded from kinetic analyses.
The stated method involves arterial plasma input functions corrected for metabolites and comparison of three kinetic approaches using Akaike model selection criteria. These descriptions indicate how the investigators intended to derive a model-based PET outcome. They do not reveal which model was selected, how well it fit, or how much uncertainty surrounded the estimates. Those results are not reported in the registry record.
Because the study is single-group and has no separate comparator arm, it cannot be read as a randomized estimate of a difference between treatments or populations. Its stated question concerns measurement in healthy volunteers. The record offers no outcome comparison with people with Alzheimer disease, despite mentioning Alzheimer disease in the background and listing it among the conditions.
The entry lists five outcome measures and zero analyses, but it does not provide outcome-level results. This means the registry information supports interpretation of the study’s aims and planned measurement framework, not a conclusion about the numerical findings. A completed status indicates the registry’s recorded status; it does not substitute for reporting results.
In general, a mean describes the central value of a continuous measure, while a standard deviation describes the spread of individual observations around that mean. Neither statistic alone fully characterizes uncertainty in an estimated mean; a confidence interval would also depend on the analysis and available data. No confidence intervals, standard errors, or other precision estimates are reported for the primary endpoint. No recalculated results are available to compare with a sponsor analysis.
The background presents a rationale for studying I2BS, including prior interest in neurological and psychiatric conditions. That rationale is not evidence of an effect in this study. The record’s stated population is healthy volunteers, and it provides no disease-group data. The posted information therefore leaves unanswered both the actual regional values and how reproducible or precise those values were in this sample.
9. Statistical Methods Explained
What does the PET outcome represent?
The primary measure is a regional PET-derived quantity intended to describe I2BS density and distribution. The record names VT and BP as possible output parameters and gives mL/cm^3 as the unit for the primary measure. In general, PET records a tracer-related signal over time. A kinetic model uses the time course, together with information about tracer availability in plasma, to estimate quantities that describe distribution or binding. Those estimates are model-dependent rather than direct counts of binding sites.
The registry describes arterial plasma input functions corrected for metabolites. In general, an input function represents tracer availability in blood over time; metabolite correction is intended to distinguish the parent tracer from radiolabeled metabolites that may also be present. The record does not report the actual input-function data, correction procedures in detail, or quality checks.
Why compare kinetic models?
The described candidate approaches are 1TCM, 2TCM, and MA. A compartmental model represents tracer behavior using compartments and transfers between them. A one-tissue model uses a simpler representation than a two-tissue model; a multilinear approach uses a different mathematical form to relate observed time-course data to estimated parameters. In general, a model should be sufficiently flexible to describe the data without adding complexity that is not supported by them.
The registry says Akaike model selection criteria were used to determine the most appropriate model. In general, this criterion compares model fit while accounting for model complexity. It can help select among candidate descriptions of the same data, but the criterion does not itself establish that a model is biologically correct. The record does not report the criterion values, the selected model for each region, or whether the same model was selected consistently. Although the primary outcome title includes “1TCM Model,” the description also specifies three candidate models; the selection results are not reported in the registry record.
What do mean and standard deviation convey?
The primary endpoint is specified as a mean with standard deviation. In general, the mean summarizes the average value in the analyzed observations, and the standard deviation describes their dispersion. A standard deviation is not the same as a confidence interval: it describes variation among measurements, whereas a confidence interval describes uncertainty about an estimated quantity under an analysis model. The registry does not report endpoint values, confidence intervals, or other uncertainty measures.
The record also lists secondary outcomes concerning intra- and inter-subject variability in brain expression, measured using coefficient of variability (%COV) determined from VT or BP, and peripheral distribution using VT or BP. In general, within-subject variability describes repeatability across measurements in the same participant, while between-subject variability describes variation across participants. A coefficient of variability expresses variability relative to a measure’s scale. The actual estimates and the procedures for obtaining repeat measurements are not reported in the registry record.
Why does over-dispersion matter in general?
Over-dispersion is a general concern for outcomes whose observed variability is greater than the statistical model assumes. If a model understates variability, its uncertainty estimates can be too small and inferential results can appear more precise than warranted. The primary endpoint in this record is continuous, and no over-dispersion assessment is reported. This concept is therefore a general statistical consideration, not a reported finding about this study.
What can be inferred from the analysis record?
The registry lists zero analyses. It does not provide a statistical analysis plan, a description of the final analysis set, model diagnostics, missing-data procedures, or inferential tests. The methods description gives the intended kinetic-model framework, but not the results of applying it. No effect estimates or p-values are reported, so there is no basis in the registry record for interpreting statistical significance or comparing sponsor-reported and recalculated estimates.
In general, confidence intervals are useful because they show a range of estimates compatible with the data and the assumptions of an analysis. Their width depends on factors such as the amount of information and the variability in the measurements. A narrow interval indicates greater precision than a wide interval, but neither guarantees that the model or measurement is valid. No confidence intervals are reported for this study’s primary endpoint.
For any planning illustration based on an observed effect, the illustration would depend on assumptions about the target effect, variability, significance level, and allocation. Such calculations are not the same as observed power and do not replace the study’s own design justification. The registry record does not report a protocol sample-size justification, and no result-based planning values are reported in the entries.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, including the primary regional-density and distribution endpoint and secondary outcomes concerning variability and peripheral distribution. It does not report a multiplicity strategy, such as whether analyses across brain regions or across outcome measures were treated as confirmatory, adjusted for multiple testing, or considered exploratory. Without reported test results or an analysis plan, the implications of multiple comparisons cannot be assessed.
The record lists zero analyses and does not report primary or secondary outcome values. It also does not describe a hierarchy of endpoints, prespecified contrasts, or rules for selecting among VT and BP. The methods description names alternative kinetic models and says Akaike model selection criteria were used, but the selected models and their results are not reported. No adjustment for model selection or regional comparisons is described.
Missing-data handling is not reported in the registry record. There is no account of incomplete scans, unusable imaging data, missing arterial samples, or how such observations may have been handled. The number enrolled is 20, while 18 are listed at risk in the adverse-event record; the registry does not explain whether this reflects endpoint availability, participation in a particular procedure, or another reason. It would be inappropriate to infer the primary analysis denominator from either count.
The analysis population is also not described. The record does not state whether analyses were based on all enrolled participants, participants who completed imaging, or another defined group. No sensitivity analyses or missing-data assumptions are reported. These omissions limit assessment of whether the reported endpoint, if available elsewhere, would represent all enrolled volunteers or only a subset.
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 |
|---|---|---|---|
| Healthy Volunteers | 0 | 18 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Healthy Volunteers | 0 of 18 |
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 |
|---|---|
| Healthy Volunteers | 0 of 18 |
The adverse-event entry lists Healthy Volunteers as the group. For serious adverse events, 18 participants are listed as at risk and 0 as affected. For other adverse events, 18 are listed as at risk and 0 as affected. Deaths are listed as 0, and no serious adverse-event terms are listed.
These figures describe the counts recorded in this registry entry; they do not establish that every participant enrolled was assessed for every event category. The enrollment is 20, whereas the at-risk counts are 18. The record does not explain this difference, define the event-collection period, or say how the at-risk population was determined. It also does not provide a narrative safety assessment or details about event ascertainment.
A recorded count of 0 affected participants means that no affected participants are listed in the registry fields for those categories. It should not be read as proof that no event of any kind occurred, nor does it establish the safety of an intervention. In particular, the registry lists both a radiotracer and drug interventions, but does not connect the adverse-event counts to specific procedures or interventions. The serious-event figures should therefore be interpreted narrowly as the posted counts, with the reporting and population details not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry describes an early-phase imaging study intended to quantify and localize I2BS in healthy volunteers. It identifies a PET-based approach using [11C]BU99008 and a kinetic-analysis framework involving arterial plasma input functions, metabolite correction, and consideration of alternative models. These details clarify the scientific question and the intended measurement strategy.
The record does not report the primary outcome values, standard deviations, regional estimates, or analyses. It therefore does not show the numerical distribution of I2BS in the participants, how much measurements varied, or how precisely any mean was estimated. The completed status does not fill that results gap. The listed five outcome measures and zero analyses likewise do not supply estimates or statistical tests.
The study does not provide a randomized or like-for-like comparison between groups. As a result, the registry entry cannot support a treatment-effect interpretation or a comparison between healthy volunteers and people with Alzheimer disease. Alzheimer disease is mentioned in the background and listed among the conditions, but the described study population is healthy volunteers and no disease-group outcome is reported.
In general, a measurement study can contribute information about how an imaging quantity is defined and estimated. Its conclusions depend on the quality of the measurements, model fit, analysis population, and uncertainty estimates. Those result-level details are unavailable in the registry record. The listed model-selection approach describes a method, not evidence that one model was selected or that its estimates were reliable.
The study’s scientific rationale discusses I2BS in relation to astrocytes and prior interest in neurodegenerative and other conditions. That background should be distinguished from evidence generated by this study. The record does not report whether the intended measurements were associated with any clinical characteristic, nor does it establish diagnostic, prognostic, or therapeutic significance. The most defensible reading is limited to the study’s stated aim and methods, alongside the absence of posted primary results.
13. Why This Trial Matters Statistically
This study raises a statistical issue common to molecular imaging: a biological target is not measured as a direct count, but through a tracer signal interpreted using a kinetic model. The registry’s description makes that distinction visible. It identifies regional time-activity data, arterial plasma input functions corrected for metabolites, and alternative modeling approaches used to derive a PET parameter.
Model choice matters because estimates can depend on how tracer behavior is represented. Comparing 1TCM, 2TCM, and MA using Akaike model selection criteria is a stated part of the analysis approach. In general, model selection balances fit and complexity; a selected model is still an approximation, and its assumptions should be considered when interpreting the resulting measure. Here, the selection criteria and resulting estimates are not reported, so readers cannot assess the consequences of model choice.
The study also lists outcomes related to intra- and inter-subject variability. In general, repeatability and variation across participants are important when considering whether an imaging measure can be interpreted consistently. However, the registry record does not report the variability estimates or enough detail about repeat measurements to evaluate them.
The single-group design is suited to a descriptive measurement objective, but it does not provide a separate control group for a between-group treatment or disease comparison. Clear separation between a measurement aim and a causal comparison is important: a study can characterize an imaging approach without establishing clinical utility or a treatment effect. In this record, even the descriptive primary estimates are absent, which makes the methods and reporting gaps especially consequential.
Finally, the difference between enrollment and adverse-event at-risk counts, and the lack of a stated analysis population, illustrate why denominators matter. Without knowing which participants contributed to each endpoint, the precision and representativeness of outcome estimates cannot be judged. These are statistical interpretation issues, not evidence of a particular result.
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 principal limitation of interpreting this specific registry record is that it contains no primary outcome values or analysis results. The intended endpoint is defined, but regional estimates, standard deviations, confidence intervals, and model-selection results are not reported in the registry record. Thus, the record does not permit assessment of measurement magnitude or precision.
The primary outcome title names a 1TCM model, while the description says that the most appropriate model would be selected among 1TCM, 2TCM, and MA using Akaike model selection criteria. Because the selection outcomes are absent, it is not possible to determine which model was used for the reported endpoint or whether selection differed by region. The methods description also does not provide model diagnostics or input-function quality information.
The record lists enrollment of 20, but the safety entry lists 18 at risk. It does not explain the difference or report endpoint-specific denominators. Participant characteristics, eligibility criteria, completion counts, and reasons for missing data are also not reported in the registry record. The analysis population and missing-data procedures are unspecified.
The study is single-group, with allocation NA and no masking. It does not describe a separate comparator arm, so the record cannot support a between-group effect estimate. The listed interventions include [11C]BU99008, Idazoxan, and Isocarboxazid, but their roles, administration, and relationship to the outcomes are not reported.
Finally, the record does not report a statistical analysis plan, multiplicity handling, or sample-size justification. It lists five outcome measures and zero analyses. These reporting gaps constrain interpretation; they should not be filled by assumptions about the protocol or by treating completion status as evidence that results were favorable or conclusive.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers — NCT02323217.
- Registry record last updated 2021-11-15; status last verified 2021-10.
- Results first posted 2021-11-15.
- 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
NCT02323217, I2PETHV - Imidazoline2 Binding Site in Healthy Volunteers, is listed as a completed early-phase 1, single-group PET study sponsored by Imperial College London. Enrollment is 20; the recorded start date is 2015-01 and primary completion date is 2016-02. Allocation is NA and masking is none.
The primary objective is to determine regional I2BS density and distribution in healthy volunteers. The outcome is a continuous mean with standard deviation, measured in mL/cm^3 over 1 week. The methods description names VT or BP as possible PET parameters and describes arterial input functions corrected for metabolites, with consideration of 1TCM, 2TCM, and MA using Akaike model selection criteria.
The registry lists five outcome measures and zero analyses. Primary outcome estimates and analysis results are not reported in the registry record. The safety entry lists 18 at risk and 0 affected for both serious and other adverse events, with 0 deaths. The record does not explain why the at-risk count differs from enrollment.