Neuropharmacological Basis of Social Connection: The Role of Opioids: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neuropharmacological Basis of Social Connection: The Role of Opioids (NCT01672723), a randomized na study. The primary outcome is Changes in Self-reported Feelings of Connection During Naltrexone (vs. Placebo).

2. Clinical Question

The study addressed a proposed link between opioid processing and feelings of social connection. Its primary endpoint was a self-reported rating collected during laboratory visits, rather than a clinical health outcome. The registry also lists a daily self-reported connection measure, allowing the posted results to include both a laboratory task and a diary outcome. These measures capture participants’ reports in the settings and timeframes described in the registry; they do not, by themselves, establish how social connection affects health or identify the biological mechanism underlying any difference.

The primary comparison is between conditions within a crossover study, but the posted summary statistics do not include participant-level paired data. The unadjusted comparison therefore needs to be interpreted with that limitation in mind. The record does not report a more detailed analysis plan, or explain the difference between the enrollment figure and the outcome-summary counts.

3. Trial Design

The registry describes a randomized, double-blind crossover study sponsored by the University of California, Los Angeles. Its recorded status is completed. The study began in 2012-10, and primary completion was recorded in 2014-02. The phase is listed as NA. Enrollment was 34.

In a crossover design, participants take more than one assigned condition at different times, so each participant may contribute information under both conditions. The study description says participants would take naltrexone and placebo in separate conditions and complete two laboratory sessions, one for each drug condition. The registry describes the study as randomized and double-blind. It does not report the order assigned to participants, how the interval between conditions was handled, or whether any washout period was used. Those details are not reported in the registry record.

The naltrexone regimen is described as four doses over four days: 25mg/day for days 1 and 2, then 50mg/day for days 3 and 4. The description says matched placebo pills were also taken, with the two treatments together spanning eight days. The primary laboratory rating was collected on day 4 of each drug assignment. The listed daily diary endpoint covers the end of each day for eight days.

The posted primary and secondary outcome summaries each report 31 observations for naltrexone and 31 for placebo. These condition-specific counts are not an explanation of participant flow in a crossover design. The registry does not report why the counts differ from the enrollment figure, whether every participant completed both conditions, or how missing observations were handled. The original sample-size justification and the trial’s prespecified statistical analysis plan are not reported in the registry record.

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: 50 screened, 19 excluded (1 asked to be removed, 15 did not respond to additional scheduling requests or additional requests for information for the lab task, 3 reported stomach discomfort at a severe level and were removed).

First Intervention

Reasons for not completing this period:

Washout Period of 10 Days

Second Intervention

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 Changes in Self-reported Feelings of Connection During Naltrexone (vs. Placebo), measured over participants will report on their feelings of connection during two separate lab visits, on day 4 of each drug assignment.

The primary endpoint is the mean self-reported feeling of connection after participants read positive, loving messages from friends and family. Participants rated how connected, touched, and warm they felt. The ratings were averaged to make a social-connection measure, with reported internal consistency of alpha = .93. Responses used a scale from 1 to 7, anchored by not at all and very; higher ratings indicate greater reported connection in response to the messages.

This endpoint is relevant to the study question because it directly records participants’ reported emotional response to a social stimulus. It is a subjective measure, not an objective measure of social behavior or a biological assay. Its interpretation is specific to the laboratory task: it describes ratings made after reading the messages, during visits on day 4 of each drug assignment. It should not be treated as a general measure of relationships or connection outside that task.

The posted condition means are 5.92 for naltrexone and 6.47 for placebo. The unit is units on a scale. The registry reports the spread as standard error. These summaries describe the average ratings and their reported uncertainty, but do not show the distribution of individual responses or the within-participant change across conditions.

7. Results Posted in the Registry

• Naltrexone: mean 5.92 versus 6.47 on control; difference -0.55 (95% CI -1.07 to -0.03), standardized effect d = -0.53; z-test p = 0.037.

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.

Daily Self-reported Feelings of Social Connection

• 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 errors.
• Result:
  • Naltrexone: mean 5.68 versus 6.26 on control; difference -0.58 (95% CI -1.29 to 0.13), standardized effect d = -0.40; z-test p = 0.111.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Naltrexone and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcome is daily self-reported feelings of social connection. Its condition means are in the same direction as the primary laboratory comparison: the naltrexone mean is lower than the placebo mean. However, the uncertainty around the unadjusted diary comparison includes zero. Taken together, the available outcomes show a directionally similar pattern, but the diary result does not provide clear statistical confirmation of the primary contrast.

The outcomes differ in context and timing. The primary endpoint reflects ratings after reading loving messages during a laboratory visit. The secondary endpoint reflects end-of-day diary ratings over the timeframe stated in the registry. Agreement in direction across different contexts can be informative, but it does not make the measures interchangeable or establish that they capture the same underlying experience. Nor does a similar direction by itself show that the laboratory finding extends to everyday social connection.

The registry lists three outcome measures, while one secondary outcome is posted. It does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. In general, when researchers examine multiple outcomes, unadjusted results carry less weight because the chance of observing a seemingly notable result across several tests can increase. This is a general statistical concern; the record does not explain which outcomes were included in the original analysis plan or how the investigators intended to address multiplicity.

The secondary result is best treated as supporting context rather than as a separate, definitive test of the study’s broader hypothesis. Its estimate and uncertainty should be considered alongside the primary result, the crossover design, and the absence of reported paired analysis details. No additional secondary analysis results are reported in the registry record.

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

• Daily Self-reported Feelings of Social Connection

9. Statistical Interpretation

10. Statistical Methods Explained

The outcomes are continuous ratings, and the registry summarizes each condition with a mean and standard error. A mean describes the average reported score in a condition. A standard error describes the uncertainty in an estimated mean; it is not the spread of individual responses. Individual scores may be more or less variable than the standard error suggests. The registry does not provide the standard deviation for the primary outcome as a directly reported result.

What does the mean difference represent?

The reported mean difference compares the naltrexone condition with placebo, using naltrexone minus placebo. A negative estimate indicates that the posted naltrexone mean is lower than the posted placebo mean. For the primary endpoint, that unadjusted difference is -0.55. This is a difference in scale units, not a percentage change or a standardized clinical effect. It summarizes the contrast between condition means and does not reveal how individual participants changed between conditions.

The study is a crossover trial, so the same participant may contribute ratings under both conditions. In a paired analysis, the estimate and its uncertainty depend on how each participant’s ratings move together across conditions. The registry record does not provide the participant-level paired values or the correlation between measurements. The posted recalculated comparison uses unadjusted summary statistics and cannot recover that within-person information. As a result, its uncertainty may not match an analysis that appropriately uses the crossover pairing. The registry does not report an adjusted or paired analysis for comparison.

How should the confidence interval be read?

A confidence interval describes a range of values compatible with the estimate under the calculation and assumptions used. For the primary mean difference, the posted 95% interval ranges from -1.066 to -0.034. It conveys uncertainty about the size of the condition contrast: the point estimate alone should not be treated as exact. The upper limit is close to zero. The interval does not include zero in this unadjusted calculation, but the interval does not account for unreported analysis choices, missing observations, or multiplicity.

In general, confidence intervals are affected by sample size, variability, and the analysis method. For a crossover study, the pairing can also matter: if within-participant responses are related, accounting for that relationship can affect the estimated uncertainty. These are general statistical considerations, not details about the study’s actual analysis plan. That plan is not reported in the registry record.

What does an unadjusted p-value say?

The primary unadjusted p-value is 0.037. In general, a p-value measures how unusual data at least as different from a null value would be if the null model and its assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the practical importance of an estimate. The registry’s comparison is unadjusted, and the record does not report whether this was the prespecified primary test or whether other statistical tests were considered in a multiplicity plan.

The record lists three outcome measures, including the primary measure, and one secondary outcome is posted. When several outcomes or analyses are considered, the chance of at least one apparently noteworthy result can increase. In general, multiplicity procedures address that issue. No such procedure is reported, so the unadjusted p-value should be interpreted cautiously rather than as a result adjusted for all possible comparisons.

What can the reported effect size add?

The posted standardized effect size for the primary comparison is d = -0.531. A standardized effect expresses a mean difference relative to a measure of variability, making it less dependent on the original scale units. It does not make the result clinically important by itself, and its precision is not captured by the point estimate alone. Because the calculation uses posted summaries and is not a participant-level paired analysis, it should be understood as a descriptive, unadjusted recalculation rather than a reported crossover-model estimate.

The registry reports the primary measure as a mean of a continuous outcome and lists standard error as the measure of dispersion. No adjusted model, covariance structure, imputation approach, or method for handling missing outcome observations is reported in the registry record. The posted comparisons should therefore be read as limited summaries, not as a complete account of the trial’s statistical methods.

11. Confidence Intervals and Precision

The primary mean difference is -0.55, with a 95% confidence interval from -1.066 to -0.034. The interval lies below zero in the unadjusted recalculation, but its upper limit is close to zero. This means the estimate is compatible with a range of negative contrasts, including values close to no difference, under the calculation used. The interval does not establish that the effect is large, important, or generalizable beyond the measured task.

Precision concerns the range of plausible estimates, not whether a result is important. The interval is shaped by the available outcome information and the calculation’s assumptions. In this crossover study, a paired analysis would use the relationship between each participant’s ratings in the two conditions. The registry record does not include the participant-level data needed to reconstruct that relationship. Consequently, the displayed unadjusted interval should not be mistaken for a confidence interval from a reported paired analysis.

The daily diary comparison is less precise in the posted calculation: its 95% confidence interval runs from -1.293 to 0.133 and includes zero. The two outcomes are distinct measures collected in different contexts, so the diary interval does not replace the primary laboratory result. Neither interval accounts for a multiplicity adjustment, and the registry does not report the trial’s missing-data approach or analysis populations.

In general, wider intervals indicate greater uncertainty about the size of an estimate, while narrower intervals indicate more precision under the analysis assumptions. Here, the registry’s summary data support describing the primary contrast as negative in the unadjusted recalculation, while also recognizing that the interval approaches zero and that key crossover-analysis details are unavailable.

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 estimates describe participants per arm for 80% power and participants per arm for 90% power. They are planning illustrations based on the observed effect, not counts of participants actually analyzed. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses a stated fraction of the observed effect as the effect to detect. These are planning calculations, not the original trial design assumptions, which are not reported in the registry record.

In plain terms, 80% power means that, under the planning assumptions and for the effect used in that scenario, the study would have an 80% chance of detecting an effect at the specified significance level if that effect were real. The 90% power column describes a higher chance of detecting the specified effect under those same assumptions. Neither figure is a guarantee for an individual study, and neither indicates the probability that a result is true.

The rows illustrate planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants to detect with the same power under the stated assumptions. These figures are not observed power; they are prospective planning illustrations derived from the observed estimate. The registry does not report whether the original trial was designed using these assumptions or estimates.

The calculations are expressed per arm, not as total participants or total events. They use a two-arm planning framework. Because the trial itself is described as a crossover study, this illustration should not be confused with a design-specific sample-size calculation for a paired crossover analysis. The registry record does not report an original sample-size justification or the assumptions used to plan enrollment.

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 = -0.550; pooled standard deviation σ = 1.036.
2. n = 2 × (1.96 + 0.842)² × 1.036² / -0.550² = 55.7, rounded up to 56 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 <- -0.55                      # observed difference in means
sigma <- 1.03573886670338                     # 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(1672723)
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 = 56 (80% power), 75 (90% power)
 75% of observed effect: n per arm = 99 (80% power), 133 (90% power)
 50% of observed effect: n per arm = 223 (80% power), 299 (90% power)
power.t.test: 56.6 
Simulated power at n = 56 per arm: 0.794 (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

The registry lists three outcome measures and posts one secondary outcome in addition to the primary outcome. It does not report a multiplicity strategy, such as an adjustment to account for testing more than one outcome, nor does it describe a hierarchy of primary and secondary hypotheses. Without that information, the posted unadjusted p-values should not be interpreted as controlling the chance of a false-positive finding across all outcomes or analyses considered.

Missing-data methods and analysis populations are also not reported in the registry record. Enrollment was 34, while the condition summaries for the primary and secondary outcomes each report 31 observations for naltrexone and 31 for placebo. The record does not explain those counts, whether observations are paired for the same participants, or whether all enrolled participants contributed to both conditions. No imputation method, exclusion rules, or intention-to-treat population definition is reported.

These omissions are important in a crossover study. Participants may contribute repeated measurements across conditions, and missing a measurement in either period can affect which paired comparisons are available. A complete-case analysis, an analysis using all available observations, and an imputed analysis can rely on different assumptions. These are general possibilities, not descriptions of what the investigators did; the analysis approach is not reported in the registry record.

The posted summary statistics and unadjusted recalculations remain useful as descriptive evidence, but they do not answer questions about robustness to missing data, adherence, period effects, or multiplicity. The registry record does not report interim analyses, a statistical analysis plan, or procedures for addressing these issues. Those aspects cannot be inferred from the reported means and standard errors.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: stomach discomfort (8.8%).

The registry reports serious adverse events for 3 participants at risk in the naltrexone condition and 0 in the placebo condition. For other adverse events, the reported affected counts are 0 in both conditions. The record lists 34 at risk in each condition for these safety summaries. These figures describe the posted registry counts; the record does not provide further detail about event timing, severity beyond the serious classification, or whether events were considered related to treatment.

Stomach discomfort is listed as the top serious adverse-event term, at 8.8%. The record does not give additional context for that percentage in the posted summary. Death counts are not reported in the registry record. A missing death count should not be interpreted as a reported count of zero.

These safety figures are descriptive. They do not establish comparative risk, and the registry record does not report a statistical safety analysis or detailed adverse-event definitions. The condition-specific counts should be read as recorded, without combining denominators or treating the counts as a full account of the study’s safety monitoring.

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

The posted primary summaries show lower average ratings of connection after reading loving messages during the naltrexone condition than during placebo. The unadjusted mean difference is -0.55, and its confidence interval is below zero but approaches zero at its upper end. The daily diary means follow the same direction, while the interval for that secondary comparison includes zero. These findings describe the posted ratings in the specific settings and timeframes recorded.

They do not establish that naltrexone changes social relationships generally, that a particular biological mechanism caused the ratings, or that the results apply to people outside this study. The endpoint is self-reported and tied to a laboratory task; the diary outcome is also self-reported. Neither is a direct measure of health or of the quality of a person’s relationships. The registry’s summary results do not support medical advice.

The numerical comparisons are unadjusted recalculations from posted summary statistics. The crossover design makes within-participant information relevant, but the registry does not report paired data or a paired model. It also does not report the missing-data approach, multiplicity handling, or original sample-size assumptions. These gaps limit how confidently the estimates can be treated as the trial’s definitive inferential results.

The most defensible reading is therefore bounded: the posted primary means and unadjusted estimate favor lower reported laboratory connection ratings in the naltrexone condition, with uncertainty that extends close to no difference. The secondary diary estimate points in the same direction but is less conclusive. The record does not establish the size, durability, or broader significance of any condition difference.

17. Why This Trial Matters Statistically

This trial is statistically interesting because its crossover structure creates a comparison in which each participant may experience both treatment conditions. Such designs can make within-person contrasts important: participant-level pairing can distinguish treatment-related changes from stable differences between people. But the registry posts condition means and standard errors rather than paired observations, so the key information needed to reconstruct that contrast is unavailable in the record.

The example illustrates why the design label alone is not enough to interpret an estimate. The posted unadjusted mean difference and confidence interval are based on summary statistics; they do not show how the crossover structure was handled in the original analysis. The missing paired analysis details matter especially because the primary interval approaches zero at its upper end. Readers need to distinguish a descriptive contrast from a fully documented model-based result.

The trial also illustrates the value of reading endpoint context alongside the numerical result. A laboratory response to loving messages and a daily diary rating are related to the study’s question, but they are not identical outcomes. Similar direction across them is informative as a pattern, while differences in precision and context constrain what can be inferred.

Finally, the record shows how enrollment, outcome counts, adverse-event summaries, and planning illustrations answer different questions. The registry does not explain the outcome-count difference or report the original sample-size rationale, multiplicity plan, or missing-data procedures. These are not reasons to discard the posted results; they are reasons to interpret them as limited evidence and to distinguish what is reported from what remains unknown.

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 outcome summaries do not explain why enrollment was 34 while each condition-specific outcome summary reports 31 observations. The record does not clarify whether those observations come from the same participants in both conditions, whether any participants were excluded, or how missing values were handled. This limits interpretation of both the precision and representativeness of the posted comparisons.

Although the design is crossover, participant-level paired results and the within-person association between conditions are not reported. The unadjusted recalculations therefore cannot show the result of a paired analysis. The registry also does not report order effects, period effects, carryover assessment, or a washout interval. These are relevant design and analysis details, but their absence from the record does not establish how the study handled them.

The primary and secondary measures are self-reports. The laboratory outcome is tied to reading positive messages, and the diary outcome reflects end-of-day ratings. The record does not report broader behavioral or clinical outcomes that would show whether the ratings correspond to other aspects of social connection. The secondary comparison is unadjusted, and multiplicity procedures are not reported.

The original sample-size rationale, prespecified analysis plan, analysis populations, and missing-data methods are not reported in the registry record. The safety summaries are also limited: deaths are not reported, and details about the adverse events and their relationship to treatment are not provided. These limitations call for cautious interpretation of the posted estimates rather than assumptions about unreported procedures.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Neuropharmacological Basis of Social Connection: The Role of Opioids — NCT01672723.
• Registry record last updated 2016-01-14; status last verified 2015-12.
• Results first posted 2016-01-14.
• 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

The registry record describes a completed randomized, double-blind crossover study of naltrexone and placebo, sponsored by the University of California, Los Angeles. Enrollment was 34. The primary outcome was self-reported connection after reading loving messages in a laboratory task; a daily diary connection measure was also posted.

The primary condition means were 5.92 for naltrexone and 6.47 for placebo. The unadjusted mean difference was -0.55, with a 95% confidence interval from -1.066 to -0.034 and an unadjusted p-value of 0.037. The diary outcome had a similar direction, but its unadjusted confidence interval included zero. The record does not report a paired crossover analysis, missing-data methods, multiplicity procedures, or the original sample-size justification.