Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors (NCT01778686), a randomized na study. The primary outcome is Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm.

2. Clinical Question

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group study in healthy participants. The study is marked completed and lists an enrollment of 24. The outcome entries report 8 participants for citalopram and pindolol, 8 for placebo, and 7 for acute tryptophan depletion. The registry record does not explain the difference between its enrollment figure and the arm sizes listed for this outcome.

The interventions were designed around PET scanning with [11C]Cimbi-36. For the citalopram and pindolol arm, citalopram infusion began 30 min before scanning and ran at 40 mg/h for 1 hour. Pindolol administration began 3 days before scanning, with the listed dose schedule increasing across days and continued dosing on scan day. The placebo description includes sugar tablets resembling pindolol and a NaCl infusion as placebo for Seropram. The acute tryptophan-depletion arm received an amino acid drink without tryptophan 4-5 hours before PET scanning; the placebo drink was a balanced formula containing tryptophan.

The primary outcome was measured over a 2 hours PET scan timeframe at baseline and after intervention. The record describes three arms but does not report detailed allocation methods, masking roles, or a protocol for handling departures from assigned treatment. It lists no formal analysis entries. The phase is recorded as NA. The registry record does not report the trial’s sample-size justification, planned interim analyses, or a prespecified statistical analysis plan. Those omissions mean the study’s design rationale and intended inferential procedures cannot be reconstructed from the registry description.

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

Reasons for not completing this period:

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 Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm, measured over 2 hours.

The primary endpoint is mean percent change in neocortical [11C]Cimbi-36 BPND from baseline to intervention in each arm. BPND is a unitless measure derived from PET data using time-activity curves for brain tissue and blood together with kinetic modelling. Scanning was performed at baseline and after intervention, and the reported endpoint summarizes the change within each arm as a mean.

As a general statistical interpretation, a positive percent change indicates that the measured value after intervention is higher than the baseline value under the endpoint’s percent-change definition. The registry does not give individual participant measurements or the calculation formula, so the precise implementation cannot be checked from the record. The listed timeframe is 2 hours, referring to the PET measurement period.

The endpoint is relevant to the study’s imaging question because [11C]Cimbi-36 is described as an agonist PET radioligand intended to quantify 5-HT2A receptor binding. The study summary says agonist binding may provide a more functional picture of these receptors and is thought to correlate with brain serotonin levels. Those statements explain the scientific motivation; the endpoint itself measures PET-derived BPND change, not serotonin concentration directly. The record reports arm means and standard deviations, but no confidence intervals or formal between-arm estimates.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a continuous outcome summarized by a mean and standard deviation in each arm. It does not list a formal analysis, a confidence interval, or a statistical test for comparing arms. The following explanations are general statistical guidance; they do not describe an analysis that the registry record says was performed.

What does the mean describe?

A mean is a measure of the central value of observations. Here, each arm’s mean summarizes participant-level percent changes in neocortical BPND from baseline to intervention. The three reported means are 7.4, 0.6, and 3.8 for citalopram and pindolol, placebo, and acute tryptophan depletion, respectively. A mean can be influenced by unusually high or low observations, which is one reason that the spread of the data and the sample size matter when interpreting it.

What does the standard deviation describe?

As a general concept, a standard deviation describes how dispersed observations are around their mean. It is a measure of participant-level variability, not the uncertainty of the mean and not a measure of the probability that an intervention effect is real. The posted standard deviations are 16.0, 7.2, and 0.2, respectively. Their different magnitudes indicate that the observed spreads are not alike across arms. The registry does not provide individual observations, distribution plots, or information about outliers, so the reasons for the differences in spread cannot be assessed.

How would an arm comparison differ from these summaries?

A between-arm analysis would estimate a contrast between an intervention and a comparator, with uncertainty around that contrast. It would address a different question from reporting each arm’s mean separately. The registry lists a placebo group, but does not post a comparison estimate, confidence interval, or p-value. No unadjusted recalculation is reported, and the record does not provide the individual-level data needed to reconstruct one. The arm means alone do not show whether the observed differences are statistically compatible with chance variation or how precisely any contrast is estimated.

Why does uncertainty matter?

As a general explanation, a confidence interval gives a range of values compatible with a statistical model and the observed data at a stated confidence level. It conveys uncertainty about an estimate more directly than a point estimate alone. No confidence intervals are reported for these means or for between-arm contrasts. Consequently, the precision of the reported means and the uncertainty in comparisons cannot be quantified from this registry record. A p-value, if reported, would address a testing procedure under its assumptions; it would not by itself describe the size or practical importance of an effect. No p-value is posted for this endpoint.

What does randomization contribute?

In general, random allocation can reduce systematic differences between groups at the start of a study, on average, when it is implemented as planned. The registry identifies the allocation as randomized and the model as parallel. It does not describe the sequence-generation method, concealment, balance checks, or analysis population. Triple masking is recorded, but the record does not identify which people were masked or explain how masking was maintained. These details are not reported in the registry record, so the potential protections from randomization and masking cannot be evaluated in detail.

What can be inferred from the planning assumptions?

The registry gives assumptions for a planning illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the original trial used those methods. The record does not report the trial’s sample-size justification or its planned analysis. Any planning illustration should be understood as a hypothetical design exercise, not as observed power or as a result of this trial. The posted record does not contain a formal analysis that supports a conclusion about the intervention contrasts.

As a general matter, over-dispersion means that data vary more than a statistical model expects. If a model assumes less variability than the data contain, estimated uncertainty may be too small and inference may be overconfident. The registry reports markedly different standard deviations across arms, but does not identify an analysis model or report a dispersion assessment. It is therefore not possible to say whether over-dispersion was assessed or how it might have affected any analysis. No model details should be inferred from the endpoint description’s mention of kinetic modelling, which concerns deriving BPND from PET and blood time-activity curves rather than necessarily describing the statistical comparison of arms.

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("Citalopram and Pindolol", "Placebo", "Acute Tryptophan Depletion")
n   <- c(8, 8, 7)
m   <- c(7.4, 0.6, 3.8)
sp  <- c(16, 7.2, 0.2)
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  Citalopram and Pindolol  8  7.400  16.000  -5.976  20.776
CARM  Placebo  8  0.600  7.200  -5.419  6.619
CARM  Acute Tryptophan Depletion  7  3.800  0.200  3.615  3.985

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no secondary outcomes. It lists no formal analysis entries for the posted outcome. No multiplicity adjustment or strategy for handling multiple comparisons is reported in the registry record. Because the record does not post formal between-arm tests, it also does not establish which comparisons, if any, were planned as confirmatory. The stated sample-size planning assumptions describe a two-arm planning illustration, not a reported statistical analysis plan.

Missing-data handling is not reported in the registry record. The outcome entries give arm sizes of 8 for citalopram and pindolol, 8 for placebo, and 7 for acute tryptophan depletion. The record does not say whether these counts represent everyone randomized, everyone scanned, or everyone included in the endpoint summary. It does not describe withdrawals, incomplete scans, unusable measurements, exclusions, or imputation. No missingness pattern can therefore be characterized from the posted information.

The registry record does not report an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. It also does not say whether participants were analyzed according to randomized assignment or according to the intervention received. The safety information lists 8 participants at risk in each arm, including acute tryptophan depletion, unlike that arm’s outcome entry of 7. The record does not explain this difference. These gaps limit interpretation of which participants contributed to each result and how representative the analyzed measurements may be.

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.

Most frequent non-serious adverse event terms

The serious adverse event record lists zero serious adverse events in each of the three arms and zero deaths in each arm. The recorded at-risk counts are 8 for citalopram and pindolol, 8 for placebo, and 8 for acute tryptophan depletion. No serious adverse event terms are listed. These entries describe what was recorded in the registry; they do not establish that serious events are impossible or that an intervention is free of risk.

The record separately reports other adverse events: zero in citalopram and pindolol, zero in placebo, and one in acute tryptophan depletion. It does not provide a term for that other event in the information available for this summary, nor does it establish that the event was caused by the intervention. The safety counts use an at-risk count of 8 in the acute tryptophan-depletion arm, while the outcome entry lists 7 participants for that arm. The registry record does not explain the difference, so the safety and outcome denominators should be read as separate entries.

As a general statistical point, observing no serious events in a small study does not precisely determine the frequency of uncommon harms. These safety observations are descriptive and should not be interpreted as a comprehensive safety assessment.

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

The result is a set of arm-specific summaries of mean percent change in neocortical [11C]Cimbi-36 BPND after intervention. The reported means are 7.4 for citalopram and pindolol, 0.6 for placebo, and 3.8 for acute tryptophan depletion. They describe the recorded PET outcome in the study’s healthy participants. The reported standard deviations describe variability within each arm, and differ across the arms.

The result does not provide a formal estimate of how much an intervention changed BPND relative to placebo. The registry record contains no reported between-arm estimate, confidence interval, or p-value. The observed arm means therefore cannot establish whether the interventions differ statistically, nor can they quantify the precision of a contrast. The record also does not report participant-level data or sufficient analysis details to reproduce an inferential comparison.

The result does not directly measure brain serotonin levels. The registry summary says [11C]Cimbi-36 binding is thought to correlate with brain serotonin levels and that agonist binding may provide a more functional picture of 5-HT2A receptors. Those statements express the study’s rationale; they do not establish that the posted BPND changes correspond to a specific serotonin change or clinical outcome. The record does not report a clinical endpoint or evidence about treatment benefit for depression, schizophrenia, or another disease.

The study’s setting and size also matter to interpretation. It enrolled healthy participants, and the listed outcome arm sizes are 8, 8, and 7. These results should not be assumed to apply to people with a disease or to other settings. The registry does not report the sample-size justification, planned analysis, missing-data approach, or detailed masking procedures. Taken together, the posted data support a descriptive account of imaging measurements, but not a strong conclusion about intervention effects or clinical relevance.

14. Why This Trial Matters Statistically

This study is statistically notable because it uses a continuous PET-derived measure to examine an imaging tracer’s behavior under several intervention conditions. The primary outcome is not a conventional clinical event; it is a mean percent change in neocortical BPND, estimated from brain and blood time-activity curves using kinetic modelling. Understanding what the measurement represents is important when interpreting the numerical summaries.

The record also illustrates why arm means should not be read as treatment comparisons. Each arm has a reported mean and standard deviation, but no formal contrast or uncertainty interval is posted. Point estimates can be described, yet their differences alone do not show how precisely the study estimates an intervention effect. The distinct spreads across arms reinforce the need to consider variability alongside the means.

More broadly, the registry record separates the scientific rationale from what the endpoint directly measures. The study summary describes interest in 5-HT2A receptor function and a possible relationship between tracer binding and serotonin levels. The posted outcome is BPND change, not a direct measurement of serotonin or a clinical outcome. This distinction helps prevent a mechanistic imaging result from being interpreted as proof of clinical benefit.

The study also highlights the value of reporting analysis populations, missing-data methods, comparison estimates, confidence intervals, and masking details. Those details are not reported in the registry record. Their absence limits readers’ ability to assess precision, reproducibility, and the implications of different arm denominators. The findings are therefore useful as descriptive evidence about the recorded imaging endpoint, while inferential and clinical conclusions remain limited.

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. The population is listed as healthy, so the results do not directly describe people with depression, schizophrenia, or other conditions mentioned in the study rationale. The endpoint is an imaging measure, and the registry does not report a clinical outcome or direct measurement of brain serotonin. The proposed relationship between agonist binding and serotonin is described as a rationale, not as a validated result of the posted endpoint.

The posted results provide arm means and standard deviations but no confidence intervals, p-values, or formal between-arm estimates. As a result, the precision of the means and the uncertainty around intervention contrasts cannot be assessed from the record. The arm sizes listed for the outcome are 8, 8, and 7, while the safety record lists an at-risk count of 8 in each arm. The record does not explain the difference for acute tryptophan depletion.

Important design and analysis details are not reported in the registry record, including the allocation procedure, the identities of people masked, the analysis population, missing-data handling, sample-size justification, and statistical analysis plan. The record also does not provide participant-level measurements, information about exclusions or incomplete scans, or a distributional assessment. Although the study is marked randomized and triple-masked, the available description does not allow a detailed assessment of how those features were implemented. These limitations do not erase the descriptive results, but they restrict the strength and scope of conclusions that can be drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors — NCT01778686.
• Registry record last updated 2025-02-20; status last verified 2025-01.
• Results first posted 2024-10-09.
• 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

The registry record describes a completed randomized, triple-masked, parallel-group study in healthy participants, with an enrollment of 24. It evaluated [11C]Cimbi-36 PET binding in relation to citalopram and pindolol, placebo, and acute tryptophan depletion. The primary outcome was mean percent change in neocortical BPND from baseline to intervention during a 2 hours PET measurement period.

The posted outcome means are 7.4, 0.6, and 3.8, with standard deviations of 16.0, 7.2, and 0.2, respectively. Outcome arm sizes are 8, 8, and 7. No formal endpoint analyses or between-arm estimates are reported. The safety record lists zero serious adverse events and zero deaths in each arm, with one other adverse event in acute tryptophan depletion. The record does not report the statistical analysis plan, missing-data methods, or a sample-size justification.