An Open-Label Study of Naltrexone in Adults With Attention Deficit Hyperactivity Disorder.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Study of Naltrexone in Adults With Attention Deficit Hyperactivity Disorder. (NCT01873729), a na phase 4 study. The primary outcome is Change in Adult Investigator Symptom Rating Scale (AISRS) Scores From Baseline.

2. Clinical Question

The registry description states that the primary aim was to assess naltrexone monotherapy for ADHD in adults. Its stated rationale is that medications increasing dopamine are often effective in treating adult ADHD and that naltrexone, described as a kappa opioid receptor antagonist, increases dopamine in the brain. These are the registry’s rationale and prediction, not findings established by the outcome data reported in the record.

The central statistical question is therefore about within-group change over time. It is not a comparison of naltrexone with placebo, usual care, or another treatment. Without a concurrent comparison group, any observed change could not by itself distinguish a treatment effect from other explanations, such as natural variation or changes over time. The record does not report numerical AISRS changes with which to characterize even that within-group pattern.

3. Trial Design

This is a Phase 4, open-label, single-group study of naltrexone in adults with ADHD. The registry lists Massachusetts General Hospital as sponsor and records the study as completed. The study start is recorded as 2013-11 and primary completion as 2016-06. Enrollment was 3.

Allocation is listed as not applicable, masking as none, and the model as single group. Those design features mean the record does not describe random assignment or a blinded comparison. The intervention is naltrexone, and the arm description names naltrexone alone. The primary endpoint is change in AISRS score from baseline to six weeks.

For interpretation, the distinction between a single-group study and a controlled comparison is important. Each participant’s baseline measurement can provide a reference for later measurement, but baseline is not an untreated group observed over the same period. A change over time can be described as a within-group change; it cannot, on its own, isolate the effect of the intervention from other influences.

The registry lists Clinical Global Impression (CGI) as a secondary outcome and reports 2 outcome measures. It reports 0 analyses. Numerical outcome estimates, participant-level results, and details of the statistical analysis are not reported in the registry record. The record also does not report the basis for the enrollment, the intended analysis population, or further details about how the study was conducted. Those omissions limit assessment of how the planned study and its analyses relate to the posted results.

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 Change in Adult Investigator Symptom Rating Scale (AISRS) Scores From Baseline, measured over Baseline and Six weeks.

The primary endpoint is change in Adult Investigator Symptom Rating Scale (AISRS) score from baseline to six weeks. The registry describes AISRS as an 18-item clinician rating scale covering individual ADHD symptoms. Each item is rated from 0 (none) to 3 (severe), and the total score ranges from 0 (no ADHD symptoms) to 54 (extremely severe ADHD symptoms).

A change score compares a participant’s measurement at follow-up with that participant’s baseline measurement. A group mean change summarizes the average change among the participants included in the analysis. The registry identifies the endpoint as a mean of a continuous measure and identifies standard deviation as its dispersion measure. The standard deviation describes variation among participant measurements; it is not a measure of the precision of the mean.

Using a clinician-rated symptom scale provides a structured way to quantify symptom severity and track it over time. Interpreting a change requires the actual estimate, its variability, and information about who was included in the analysis. Those numerical results are not reported in the registry record, so the direction, size, and precision of the mean change cannot be described. The record also does not report a threshold for a clinically important change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is AISRS?

The primary endpoint is a continuous score, and the registry specifies that the group summary is a mean with standard deviation. A mean describes the arithmetic average of the measurements being analyzed. Standard deviation describes how spread out those measurements are around their mean. These statistics answer different questions: the mean locates the group average, while the standard deviation describes variability among observations.

The endpoint is change from baseline to six weeks, rather than a score at only one time. In general, a change score is calculated for each participant by comparing the follow-up measurement with baseline, after which a group summary can be made. The registry record does not report the individual measurements, the mean change, or its standard deviation. It therefore does not permit an independent assessment of the observed change or the distribution of changes.

What would an interval estimate convey?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. It gives a range of values compatible with the observed data and method; it is not a guarantee that the true value lies within that particular interval. For a mean change, an interval would help readers assess precision in addition to the estimated direction and size. No confidence interval for the primary endpoint is reported in the registry record.

A small amount of data generally gives less information about a population mean than a larger amount, all else being equal. Here, enrollment is 3, but the number included in the primary endpoint analysis is not reported in the registry record. The precision of a mean depends not only on enrollment but also on the observations’ variability and which participants contributed. Without the endpoint estimate, dispersion, and analysis count, precision cannot be evaluated.

Why does the design matter for inference?

General statistical explanation: a single-group pre-post analysis describes change within the same group over time. A concurrent control group can help distinguish changes associated with the intervention from background changes, but this study is recorded as single-group with no allocation. Baseline is a measurement taken before follow-up, not a separate group that represents the counterfactual course over the same period. Thus, within-group change and a controlled treatment comparison are different estimands, or quantities being estimated.

Open-label status means masking was none. General statistical explanation: when participants and assessors know the treatment, expectations or assessment processes may influence subjective or clinician-rated measurements. This is a consideration in interpreting a clinician-rated symptom scale, not evidence that any particular score was biased. The registry record does not describe additional procedures to reduce or assess such influences.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe an illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These assumptions describe a hypothetical planning framework; they do not describe the actual single-group study, which had no two-arm allocation. Such planning illustrations are not observed power and do not show how many participants were enrolled under the study’s own design. The registry record does not report a sample-size justification for the trial.

General statistical explanation: a significance level is a decision threshold used in a specified testing procedure, while power is the probability of detecting an effect of a specified size under stated assumptions. Planning calculations depend on those assumptions, including the effect size and design. They do not change the amount of information actually collected, and an illustration based on an observed effect should not be interpreted as evidence that the study had adequate or inadequate power. No trial-specific power calculation is reported in the registry record.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, standard errors may be too small and confidence intervals too narrow. This concept is especially relevant to analyses whose probability model imposes a particular variance structure. The primary endpoint is described as a continuous measure summarized by a mean and standard deviation; the registry record does not report a model or an over-dispersion assessment. It would therefore be inappropriate to claim that over-dispersion was present or handled.

In this study, the practical statistical limitation is more basic: the registry record does not provide numerical primary endpoint results or analysis details. Without those, readers cannot inspect the estimate, variability, uncertainty, or assumptions of an inferential procedure. General statistical concepts explain what such information would mean, but cannot substitute for the unreported results.

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("Naltrexone")
n   <- c(2)
m   <- c(-5)
sp  <- c(5.7)
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  Naltrexone  2  -5.000  5.700  -56.212  46.212

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies Clinical Global Impression (CGI) as a secondary outcome. It reports 0 analyses. Numerical results for the primary endpoint and secondary outcome are not reported in the registry record, and the record does not describe a statistical analysis plan for interpreting multiple outcomes.

General statistical explanation: when several outcomes or hypotheses are tested, the chance of obtaining at least one apparently notable result can increase if each is assessed separately without adjustment. A prespecified hierarchy or multiplicity adjustment can address some of this issue, but the appropriate approach depends on the study questions and analysis plan. The registry record does not report whether multiplicity was considered, whether a hierarchy was specified, or whether any adjustment was used. No particular approach should be assumed.

Missing-data methods are also not reported in the registry record. It does not state whether any measurements were missing, how missing observations were handled, or whether sensitivity analyses were conducted. Enrollment was 3, but the number contributing data to each outcome is not reported. Without these details, it is not possible to determine whether the analyzed participants differed from those enrolled or how missingness may affect interpretation.

The analysis population is not reported in the registry record. The record does not specify whether analyses included all enrolled participants, participants who completed follow-up, or another defined group. It also does not report an interim analysis or a statistical testing procedure. These are reporting gaps, not evidence that a particular method was or was not used.

12. 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.

The registry reports 0 serious adverse events among 3 participants at risk in the naltrexone group. It also reports 0 other adverse events among 3 participants at risk. The serious adverse event terms list is empty. The death count is not reported in the registry record.

These figures describe events recorded for this group; they do not establish that the intervention is free of risk. With only 3 participants at risk, the safety observations are limited, and the registry does not provide event-level details or additional context for interpreting surveillance. A count of 0 means no events were recorded in the reported category for the participants at risk; it does not show that an event could not occur or that a larger group would have the same experience.

The registry’s adverse-event figures should also be kept distinct from the efficacy endpoint. They do not provide information about AISRS change, and the lack of reported serious events does not resolve the absence of numerical symptom results. Safety and symptom outcomes answer different questions and require their own data and interpretation.

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

The record describes a completed Phase 4 study of naltrexone in adults with ADHD. It was open-label and single-group, enrolled 3 participants, and identified change in AISRS score from baseline to six weeks as the primary endpoint. The registry also identifies CGI as a secondary outcome and records 2 outcome measures.

The central numerical result needed to interpret the primary endpoint is not reported in the registry record. There is no mean change, standard deviation, confidence interval, or test result. The posted information therefore does not show the direction, size, or precision of AISRS change. Numerical secondary outcome results are also not reported.

Even a numerical change in this design would describe change over time within the treated group, not a controlled comparison with an untreated or differently treated group. Without a concurrent control group, other explanations for a change cannot be separated from an intervention effect. Open-label assessment is another design feature to consider when interpreting a clinician-rated outcome, although the record does not establish that it affected any result.

The study does not establish whether naltrexone is effective or ineffective for adult ADHD. That conclusion would require results and a design capable of supporting the relevant comparison. The reported safety counts are also limited: 0 serious adverse events and 0 other adverse events among 3 participants at risk, with the death count not reported in the registry record. These observations do not establish the absence of risk.

In short, the record supplies information about the study question, design, endpoint, enrollment, and reported adverse-event counts, but not the numerical efficacy results or analysis details needed to evaluate the primary outcome. Its value for interpretation is therefore primarily descriptive rather than confirmatory.

14. Why This Trial Matters Statistically

This study is statistically notable because it makes the distinction between measuring change and estimating a treatment effect especially clear. The primary endpoint compares AISRS scores over time within a single group. That can describe a pattern of change, but without a concurrent control it cannot by itself establish what portion of that pattern is attributable to treatment rather than other influences.

The small enrollment also matters for how any estimate would be read. With 3 participants enrolled, individual observations could have substantial influence on a group average, and precision would depend on the variability and the number actually analyzed. The registry record does not report those endpoint details, so the magnitude and uncertainty of the primary result cannot be assessed.

The record also illustrates why complete outcome reporting is necessary for statistical interpretation. Naming an endpoint and its measurement scale clarifies what the study intended to assess, but readers also need the observed estimate, variability, and analysis population to understand the evidence. Those numerical results and analysis details are not reported in the registry record.

Finally, planning assumptions should not be confused with trial results or design features. The registry’s stated illustration assumes equal allocation between two arms, while the study itself is recorded as a single-group design. Keeping those descriptions separate helps prevent hypothetical planning calculations from being treated as evidence about the actual study’s precision or power.

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.

The most direct limitation for interpretation is that numerical results for the primary endpoint are not reported in the registry record. Without the mean change, standard deviation, and analysis count, the observed change and its precision cannot be described. The registry also does not report numerical results for CGI or other analysis details.

The study’s single-group, open-label design limits the kind of inference it can support. There is no concurrent control comparison, and treatment masking was none. The endpoint is clinician-rated, so knowledge of treatment is relevant context when considering measurement, although no specific effect of that knowledge is reported.

Enrollment was 3. The record does not report participant characteristics beyond the adult ADHD population, the number completing follow-up, or the number included in each outcome analysis. It also does not report eligibility details, missing-data methods, the analysis population, or reasons for any missing observations. The record does not state the sample-size justification or provide a trial-specific statistical plan.

The registry identifies 2 outcome measures and 0 analyses, but does not report how outcomes were prioritized statistically or whether multiplicity was addressed. It also does not report an interim analysis. These absent details prevent assessment of the analysis strategy, but do not establish what procedures were or were not performed outside the registry record.

Safety interpretation is limited by the small number at risk and the absence of reported event details. The registry records 0 serious adverse events and 0 other adverse events among 3 participants at risk; the death count is not reported in the registry record. These counts should not be generalized beyond the reported participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Study of Naltrexone in Adults With Attention Deficit Hyperactivity Disorder. — NCT01873729.
• Registry record last updated 2017-01-13; status last verified 2016-11.
• Results first posted 2016-09-20.
• 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 Phase 4, open-label, single-group study of naltrexone in adults with ADHD. Massachusetts General Hospital is listed as sponsor. Enrollment was 3. The study start is recorded as 2013-11 and primary completion as 2016-06.

The primary endpoint was change in AISRS score from baseline to six weeks, summarized as a mean with standard deviation. CGI was listed as a secondary outcome, and the record reports 2 outcome measures and 0 analyses. Numerical primary and secondary outcome results are not reported in the registry record.

The study had no randomized comparison and no masking. The registry reports 0 serious adverse events and 0 other adverse events among 3 participants at risk; the death count is not reported in the registry record. The design and missing numerical results limit assessment of efficacy, precision, and broader safety.