Genetic Effects on Dopamine Response to an Opiate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetic Effects on Dopamine Response to an Opiate (NCT01878006), a randomized phase 2 study. The primary outcome is 11C Raclopride Binding Potential in Caudate.

2. Clinical Question

The study addressed a genetic-response question: whether variation in the mu opioid receptor gene might be related to morphine’s effects on brain reward and subjective experience. The official title identifies the OPRM1 A118G SNP as the focus. However, the posted primary results do not report genotype-specific estimates or a comparison between genetic groups. The numerical result therefore speaks to the recorded morphine-placebo comparison among the participants included in both PET sessions, rather than establishing a genetic subgroup effect.

The registry lists pain, addiction, and genetic polymorphism among the conditions. It describes eligibility as including previous use of prescription pain pills for a medical or dental procedure. It does not report the genotype distribution, the number of participants in each genotype group, or whether genotype modified the treatment contrast. Those omissions limit how directly the title’s genetic question can be evaluated from the posted numerical results.

3. Trial Design

This was a phase 2 study recorded as completed, with randomized allocation, double masking, and a crossover model. The registry reports enrollment of 15 participants. In a crossover design, participants receive more than one study condition, allowing comparisons to be made within the same participants when the analysis accounts for the repeated observations. The record identifies morphine and placebo but does not report the order in which participants received them, the method of randomizing sequence, or the interval between study conditions.

The intervention was a morphine injection at 10 mg/70kg, and the comparator was saline injection. The primary outcome was measured 90 minutes following injection. The secondary subjective measures were recorded 60 minutes following injection. The study description also lists screening and study visits, including PET-related procedures, questionnaires, and genetic testing, but the available description is truncated. Details beyond those explicitly recorded cannot be established from the registry record.

Although enrollment was 15, the population for the primary analysis is described as only participants who completed both PET sessions, active and placebo. The outcome summaries report 10 participants for each condition. These are repeated observations in a crossover study, not evidence of separate groups of participants for each condition. The record does not explain the difference between total enrollment and the completer population or give a participant flow accounting for the analysis population.

The registry record does not report the study’s original sample-size justification, the assumptions used to design the trial, or the planned statistical model. It also does not report whether the analysis accounted for within-participant pairing, treatment sequence, period effects, or possible carryover. Those details matter because a crossover comparison depends on the relationship between measurements from the same participant. The randomized, masked design describes important features of the trial, but it does not by itself establish how the posted summaries were analyzed.

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.

Before assignment: 15 subjects were consented for the trial, but 10 subjects were found eligible to start the study.

Study Session 1

Study Session 2

Analysis population for the primary outcome, as defined in the registry: The analyses included only those subjects who completed both PET sessions (active and placebo)

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 11C Raclopride Binding Potential in Caudate, measured over 90 minutes following injection.

The primary endpoint was 11C raclopride binding potential in the caudate, reported as a mean in mCi/ml with standard deviations. Binding potential was measured through regions-of-interest analysis of PET data. The registry describes the use of parametric binding potential images obtained with the Simple Reference Tissue Model 2 and cerebellum as the reference region.

The endpoint is used as an imaging-based measure related to dopamine response. According to the registry record, reduced raclopride binding is attributed to competition with endogenous dopamine, and has been shown to be proportional to the magnitude of dopamine release. This makes binding potential an indirect brain measure for the study’s question; it is not a direct count of dopamine molecules or a direct measure of a participant’s subjective experience.

The primary outcome was assessed 90 minutes following injection. The record reports a mean of 3.25 for morphine and 3.45 for placebo, with standard deviations of 0.4 and 0.5, respectively. The posted mean difference is -0.2. The registry’s analysis population is restricted to participants who completed both PET sessions. While the record gives the measurement model and analysis population, it does not report a sponsor-conducted statistical analysis for the primary outcome or details of how repeated measurements were handled.

7. Results Posted in the Registry

• Morphine: mean 3.25 versus 3.45 on control; difference -0.20 (95% CI -0.60 to 0.20), standardized effect d = -0.44; z-test p = 0.323.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Subjective Perception of Morphine Effect - Feel Drug

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Morphine: mean 3,943 versus 176.00 on control; difference 3,767 (95% CI 3,135 to 4,399), standardized effect d = 5.23; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjective Perception of Morphine Effect - Feel High

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Morphine: mean 3,729 versus 175.00 on control; difference 3,554 (95% CI 2,773 to 4,335), standardized effect d = 3.99; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjective Perception of Morphine Effect - Like Drug

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Morphine: mean 3,079 versus 2,628 on control; difference 450.40 (95% CI -856.35 to 1,757), standardized effect d = 0.30; z-test p = 0.499.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Morphine and the control. The interval gives the range of effects that remain compatible with the data.

The secondary measures concern participants’ subjective perceptions of morphine. Across the detailed numerical results, the measures of feeling the drug and feeling high show positive contrasts favoring higher scores after morphine, while the contrast for liking the drug is less precise and is compatible with no difference. This pattern is not identical to the primary PET result, whose interval includes zero. Subjective reports and caudate binding potential capture different aspects of response, so different patterns do not by themselves establish a contradiction.

The registry lists four named secondary outcomes, including wanting more, but detailed numerical results are not reported in the registry record for every listed outcome. It also records eight outcome measures overall, while the available detailed secondary results cover fewer measures. The record does not explain the relationship between the named outcomes and all outcome measures, nor does it report why some numerical results are absent.

The secondary findings should carry less weight as confirmatory evidence because the registry lists multiple outcomes and reports no multiplicity adjustment, prespecified hierarchy, or analysis plan. When multiple hypotheses are examined, the chance of at least one apparently strong result can increase unless the analysis addresses that issue. This is a general statistical concern; the registry record does not say whether a correction was considered outside the posted results.

In addition, the detailed secondary comparisons are unadjusted summary-statistic estimates from a small completer population in a crossover design. The record does not show within-participant differences or a sponsor-reported repeated-measures analysis for these outcomes. The secondary results can describe the pattern in the posted summaries, but they do not establish that the treatment effects are reproducible, that the outcomes were equally important in the study plan, or that the subjective measures explain the primary imaging result.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Subjective Perception of Morphine Effect - Feel Drug
• Subjective Perception of Morphine Effect - Feel High
• Subjective Perception of Morphine Effect - Like Drug
• Subjective Perception of Morphine Effect - Want More

9. Statistical Interpretation

10. Statistical Methods Explained

The registry describes a continuous primary measure summarized by means and standard deviations. The posted comparison is a difference in means between morphine and placebo. A mean difference preserves the endpoint’s original units, mCi/ml, so its interpretation remains tied to the PET binding-potential scale. The negative estimate indicates that the posted morphine mean was lower than the placebo mean; it does not, on its own, establish that the difference is reliable or meaningful.

What does a confidence interval communicate?

A confidence interval represents uncertainty around an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision, while a wider interval indicates less precision. In this trial, the primary interval includes zero and extends in both directions around the estimated difference. That means the posted summaries do not pin down a single direction of the contrast with high precision. The interval is not a range containing a fixed proportion of individual participant measurements, and it does not express the probability that the true effect lies within its bounds.

The registry reports standard deviations for each condition. A standard deviation describes variability among measurements within a condition; it is not the uncertainty of the estimated mean difference. The standard errors shown with the comparisons relate to the uncertainty of the arm means in the posted summary-statistic calculations. They do not provide the within-participant covariance needed to reconstruct a paired crossover standard error. Because each participant completed both conditions, the dependence between measurements is relevant to an analysis that uses the crossover structure.

Why does the crossover structure matter?

In a crossover study, a participant can serve as their own comparator because measurements under different conditions come from the same person. A paired analysis uses the difference within each participant and can account for stable participant-level characteristics shared across periods. The size of the gain in precision depends in part on how strongly measurements under the different conditions are related. The registry record does not report that relationship, participant-level changes, treatment sequence, period effects, or the statistical model used by the sponsor.

The posted arm means and standard deviations alone cannot reveal the distribution of within-person differences. The displayed comparisons are unadjusted recalculations from the posted summary statistics, not reported analyses from the registry. They should therefore be read as summary-based comparisons rather than as a substitute for a prespecified crossover analysis. The record lists no reported analyses. It also does not state whether the study’s own analysis incorporated pairing, handled period or sequence effects, or used an alternative approach.

How should the p-value be read?

An unadjusted p-value measures the compatibility of the observed statistic with a specified null hypothesis under the calculation’s assumptions. A smaller p-value indicates less compatibility with that null model; it is not the probability that the null hypothesis is true, nor is it a measure of the magnitude or clinical importance of an effect. The primary p-value is 0.323. The secondary p-values reported as <0.001 apply to the corresponding unadjusted subjective-outcome comparisons. Because multiple secondary outcomes are recorded and no multiplicity procedure is reported, those values do not establish confirmatory evidence across the outcome family.

The word unadjusted has more than one use in clinical results. Here, it identifies comparisons not adjusted for multiplicity or other covariates in the posted calculation. The registry does not provide an adjusted treatment estimate, a model specification, or a correction for the repeated-measures design. No new model can be inferred from the means and standard deviations. In particular, the posted comparisons should not be described as adjusted for genotype, baseline values, treatment sequence, or other factors.

What can standardized effects add?

A standardized mean difference expresses an estimated contrast relative to a measure of variability, which can make measures on different scales easier to compare in general. The registry gives standardized effect estimates for the primary and secondary comparisons. Such values do not replace the original-unit mean differences, and their interpretation depends on how variability is defined. In a crossover trial, a standardized effect based on pooled arm standard deviations does not necessarily reflect the variability of within-participant differences. It should not be interpreted as a direct measure of biological importance.

For the primary outcome, the reported standardized estimate is -0.442. That estimate is a derived summary, not an additional observed endpoint. It does not resolve the uncertainty reflected in the confidence interval or provide missing information about the paired analysis. Similarly, the standardized values for subjective outcomes do not address multiplicity, participant selection, or the generalizability of the small completer population.

What does the sample-size calculation describe?

The sample-size figures are planning illustrations based on the observed effect, rather than a reconstruction of the trial’s original design. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The calculations give participants per arm for continuous outcomes. They do not describe the number enrolled in the crossover trial, and the equal-allocation illustration does not mirror the within-participant structure of this study.

These planning calculations use an observed effect as their starting point, so they are sensitive to the estimate from a small study. They do not establish that the original sample was adequate or inadequate, and the registry record does not report the assumptions used in its own design. The power labels refer to the probability, under the stated planning model and effect assumption, of detecting a difference at the stated significance level. These calculations are not observed power and do not measure the strength of evidence after the trial.

11. Confidence Intervals and Precision

Precision is most directly conveyed by the confidence interval around the estimated primary mean difference. The point estimate is -0.2, and the interval runs from -0.597 to 0.197. Because zero lies within that interval, the data do not precisely distinguish a negative difference from no difference or a positive difference under the posted calculation. The interval’s span shows that the estimate remains uncertain in relation to the scale of the measured endpoint.

The reported p-value of 0.323 is consistent with the interval including zero under the unadjusted calculation. Neither the interval nor the p-value establishes equivalence. An equivalence conclusion would require a prespecified margin and an analysis designed to evaluate whether plausible effects fall within that margin; the registry record does not report such a margin or analysis.

The two condition means are based on 10 participants each in the primary summaries, and the analysis population is limited to people who completed both PET sessions. The condition-level standard deviations describe variation in measurements, but they do not show how each participant’s active and placebo values were related. That missing within-person information prevents the reader from assessing how much the crossover pairing might change the precision of a paired estimate.

Confidence intervals for the secondary outcomes also differ in precision and location, but they are unadjusted and relate to subjective scales rather than the primary imaging outcome. Their apparent precision should be considered alongside the small analysis population, multiple outcomes, and the lack of reported analysis details. A narrow interval on one posted comparison cannot compensate for limitations in the analysis population or establish that the result will generalize to other populations.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are expressed as participants per arm for the continuous outcomes. They are not total event counts, because the outcomes are not time-to-event measures. The calculations use the assumptions stated for the planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The record does not report the sample-size assumptions used when the trial was originally designed.

The 80% power column indicates the number of participants per arm the planning model estimates would be needed to have an 80% chance of detecting the specified effect if the assumptions hold. The 90% power column uses a higher target probability of detection and therefore generally requires more participants for the same effect assumption. These are conditional planning calculations, not guarantees that a future study will produce a particular result.

The scenarios consider the full observed effect and smaller fractions of it. Smaller effects require more participants to detect at the same power target, all else held to the stated assumptions. That relationship is a general feature of statistical planning: subtle contrasts are harder to distinguish from random variation than larger contrasts.

These sample-size figures are not observed power. They are illustrations derived from the observed effect, not a report of the trial’s original design rationale. Because the study is a crossover trial but the illustration assumes equal allocation between two arms, the figures should not be read as a crossover-specific design calculation. The registry does not report a separate sample-size justification based on paired measurements or within-participant variability.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.200; pooled standard deviation σ = 0.453.
2. n = 2 × (1.96 + 0.842)² × 0.453² / -0.200² = 80.5, rounded up to 81 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.2                      # observed difference in means
sigma <- 0.452769256906871                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1878006)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 81 (80% power), 108 (90% power)
 75% of observed effect: n per arm = 144 (80% power), 192 (90% power)
 50% of observed effect: n per arm = 322 (80% power), 431 (90% power)
power.t.test: 81.4 
Simulated power at n = 81 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or hypotheses are evaluated. The registry lists the primary imaging endpoint and multiple secondary subjective outcomes, and it records eight outcome measures. The record does not report a multiplicity adjustment, a hierarchy among endpoints, or a statistical plan identifying which comparisons were confirmatory. The secondary p-values are therefore best understood as unadjusted results for individual comparisons, not as a family-wise assessment of all outcomes.

The registry’s reported analyses list is empty. As a result, there is no sponsor analysis in the record to compare with the unadjusted summary-statistic recalculations. The record does not describe model terms, analysis code, a rule for handling multiple comparisons, or a method for controlling false-positive findings. It also does not report interim analyses or stopping rules; those details are not reported in the registry record.

For missing data and analysis populations, the primary outcome description says that analyses included only participants who completed both PET sessions. The primary summaries report 10 participants per condition, while enrollment is 15. The record does not provide a participant flow accounting, reasons for noncompletion, or a missing-data method. It does not say whether the same completer restriction was applied to every secondary outcome, or whether any participants had incomplete subjective measures.

The crossover structure also makes the analysis population relevant: participants with a measurement from only one condition may not contribute to a complete-pair analysis, but the registry does not describe how incomplete pairs were treated. It does not report sensitivity analyses, imputation, or assumptions about missingness. Without those details, the extent to which missing outcomes could affect the posted estimates cannot be assessed from the record.

The record therefore allows a limited description of who contributed to the primary summaries, but not a full assessment of outcome availability or analytical choices. These reporting gaps do not demonstrate that a particular method was or was not used; they mean the method is not reported in the registry record.

15. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The posted safety figures report zero serious adverse events in both the morphine and placebo groups, and zero deaths in both groups. For other adverse events, the registry reports six affected participants among 10 at risk in the morphine group and none among 10 at risk in the placebo group. The record does not list serious adverse event terms.

These are descriptive counts from a small study population. A count of zero serious adverse events in the posted record does not establish that serious events cannot occur, and the difference in recorded other adverse events should not be treated as a precise estimate of risk. The record does not provide event-level descriptions for the other adverse events, their severity, timing, or relationship to study treatment. The figures should be read as the adverse-event information recorded for this trial, not as a complete characterization of safety in broader populations.

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

The posted primary result describes an uncertain difference in caudate raclopride binding potential between morphine and placebo among participants who completed both PET sessions. The mean difference is -0.2, and its confidence interval includes zero. This does not establish that the conditions are the same, nor does it establish a reliable difference. It indicates that the posted summary-based estimate is not precise enough to rule out a range of possible contrasts under its calculation assumptions.

The study’s stated motivation concerns genetic variation in the mu opioid receptor gene and dopamine response. However, the posted numerical results do not provide separate estimates by genotype or a test of interaction between genotype and treatment. The record therefore does not answer whether the OPRM1 A118G SNP alters the observed response. A title or study objective is not a substitute for genotype-specific results.

The secondary subjective measures show varying patterns, with some posted comparisons more clearly separated from zero than the primary comparison and another secondary estimate remaining uncertain. These outcomes are not interchangeable with the PET measure. They may offer context about subjective experience in the study, but unadjusted results across multiple outcomes do not establish a single coherent treatment effect or identify a biological pathway.

The results also do not determine whether morphine provides pain relief in clinical practice. The primary endpoint is an imaging measure related to dopamine release, and the listed subjective endpoints concern perceptions following injection. The registry does not report a clinical pain-efficacy comparison or a clinical outcome demonstrating benefit. No treatment recommendation follows from these statistical results.

Interpretation is further limited by the small completer population, absence of reported sponsor analyses, and lack of detail about paired crossover methods, missing outcomes, and multiplicity. The appropriate conclusion is descriptive: the record contains an uncertain primary summary-based contrast and a mixed pattern across the posted subjective measures, while key analysis and genetic subgroup results are not reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically notable because its design is a randomized, double-blind crossover, while the numerical summaries are presented by condition. Crossover studies can make efficient use of within-participant comparisons, but their analysis depends on the relationship between observations from the same person and on design details such as sequence and period. The registry record does not report those details or a sponsor analysis that would clarify how the repeated measures were handled.

The example also shows why an estimate and its precision should be read together. The primary mean difference is a concise description of the contrast, but the confidence interval includes zero and spans values on either side. The p-value alone cannot explain the magnitude, direction, or practical relevance of possible differences. Reporting the estimate with its interval makes the uncertainty more visible.

The trial also illustrates the distinction between a primary objective and multiple secondary measures. Subjective outcomes can provide useful context, but their unadjusted results have a different evidential status when several outcomes are examined and no multiplicity strategy is reported. A prominent secondary p-value should not be treated as if it were the prespecified primary result.

Finally, planning calculations based on observed effects are not a substitute for the original design rationale. They illustrate how sample requirements change as the effect to detect becomes smaller, but they do not tell whether the original enrollment target was appropriate. The registry record is useful for identifying what was measured and what summaries were posted, while its missing analysis details show why complete statistical reporting matters for interpreting small crossover studies.

18. 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 analysis is described as restricted to participants who completed both PET sessions, and the reported condition summaries each include 10 participants. The record does not account for the remaining enrolled participants or explain whether incomplete data affected any outcome. This limits assessment of selection related to study completion and the effect of missing observations.

The registry identifies a crossover design but does not report the treatment sequence, interval between conditions, participant-level paired values, or within-person correlation. It also does not report whether the statistical analysis accounted for treatment period or carryover. These details are specific to interpreting this study’s repeated-measure comparison and cannot be recovered from condition means and standard deviations alone.

The registry record lists no reported analyses. The comparisons available are unadjusted recalculations from summary statistics, so they do not establish what inferential analysis the sponsor conducted or intended. The record also does not report a multiplicity strategy, an original sample-size justification, or a prespecified statistical plan. The relationship between the eight recorded outcome measures and the available detailed results is not explained.

The genetic question is another trial-specific limitation of the posted results. Although the official title focuses on OPRM1 A118G, the numerical outcomes do not give genotype groups, genotype-specific treatment estimates, or an interaction analysis. The results therefore cannot establish the role of genotype in the primary or subjective responses.

Finally, the study population is described through eligibility criteria and a small completer sample. The registry record does not provide enough information to assess how representative the participants were of other populations or settings. These limitations concern what can be interpreted from the registry record; they do not determine what analyses may exist outside it.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Genetic Effects on Dopamine Response to an Opiate — NCT01878006.
• Registry record last updated 2021-04-01; status last verified 2021-03.
• Results first posted 2018-10-23.
• 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.

22. Record Summary

NCT01878006 is a completed phase 2 randomized, double-blind crossover study comparing morphine injection with saline placebo. Enrollment was 15. The primary outcome was caudate 11C raclopride binding potential measured 90 minutes following injection, with the primary analysis restricted to participants who completed both PET sessions.

The posted primary means were 3.25 for morphine and 3.45 for placebo. The unadjusted mean difference was -0.2, with a confidence interval that includes zero and an unadjusted p-value of 0.323. Subjective secondary outcomes show mixed levels of separation between conditions. The registry record lists no reported analyses and does not report genotype-specific results, a multiplicity strategy, or key details of the crossover analysis. The safety record reports no serious adverse events or deaths, with other adverse events recorded in the morphine group.