Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD) (NCT03757585), a randomized phase 4 study. The primary outcome is Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score.

2. Clinical Question

3. Trial Design

The registry identifies NCT03757585 as a completed, randomized, open-label, parallel-group clinical trial. It lists the phase as Phase 4 and Massachusetts General Hospital as the sponsor. The study was conducted via telepsychiatry, according to its official title. The registry lists enrollment as 54. The recorded study start was 2019-05-20, and primary completion was 2024-05-06.

The planned study duration is described as 6 weeks. Eligible participants were described as youth ages 5-17 years with NVLD or ASD and current emotional dysregulation symptoms. The registry does not report detailed baseline characteristics in the posted outcome record, so the results cannot be placed in context of the groups’ symptom distributions, demographic composition, or other clinical features from these data alone.

The parallel groups were omega-3 fatty acids plus inositol and N-acetylcysteine. Treatment was open-label, meaning the registry does not describe masking of participants or treatment providers. Random allocation can help make treatment groups comparable on average, but the registry record does not report the sequence-generation method, concealment procedure, or allocation ratio. Those details are not reported in the registry record.

The combination arm used dosing instructions based on weight, while the NAC arm used instructions based on age and formulation. Consequently, the comparison concerns the two treatment strategies as described, rather than a single ingredient against a placebo. The registry does not report adherence, changes in treatment during follow-up, or treatment exposure for individual participants.

The primary outcome was mean change in parent-completed P-YMRS score from baseline to 6 weeks. Two secondary outcomes were also posted: change in the Parent-completed Children's Depression Inventory (CDI) and change in the NIMH Clinical Global Improvement Scale (CGI). The registry lists no reported analysis records. It does not report the original statistical analysis plan or the assumptions used to set the trial’s enrollment target; those details 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: Participants may also be recruited from the referral pool of existing and new patients in the Pediatric Psychopharmacology Program and the MGH Child Psychiatry Outpatient Clinic or from the pool of children screened for participation in Protocol #2019-P-000846 ("An Open-Label Clinical Trial Conducted via Telepsychiatry of Complementary and Alternative Treatments (Omega-3 Fatty Acids and Inositol vs. N-acetylcysteine) for the Management of Emotional Dysregulation in Youth").

Overall Study

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.

Population: Equal numbers of baseline participants in each group.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score, measured over Baseline to 6 Weeks.

The primary endpoint is mean change in the parent-completed Young Mania Rating Scale score (P-YMRS) from baseline to 6 weeks. The registry describes the YMRS as an assessment of manic symptoms, with questions about the last week. It consists of 11 items rated from 0, for symptoms not present, to 4, for symptoms extremely severe; the overall score ranges from 0-60. Higher scores indicate more severe manic symptoms.

A mean change describes the average difference between a group’s score at baseline and its score at follow-up. Negative change indicates a decrease in the score, while positive change indicates an increase. Because higher scores represent more severe manic symptoms, the direction of change helps describe whether average symptom ratings moved upward or downward. It does not, by itself, establish why scores changed or whether the change is meaningful for an individual.

The registry notes that the YMRS is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to core symptoms of mania. In this trial it was used to assess manic symptoms among youth with NVLD and/or ASD who had emotional dysregulation symptoms. The endpoint therefore measures one symptom domain; it does not capture every aspect of emotional dysregulation or the full experience of participants and families.

The comparison focuses on whether average change differed between the randomized groups. It is not a comparison with no treatment, because both groups received an active intervention. The registry does not report a threshold for a clinically important change on this measure.

7. Results Posted in the Registry

• N-Acetylcysteine: mean -2.60 versus 0.00 on control; difference -2.60 (95% CI -7.76 to 2.56), standardized effect d = -0.32; 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.

Mean Change in the Parent-completed Children's Depression Inventory (CDI)

• 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:
  • N-acetylcysteine: mean -1.30 versus -3.40 on control; difference 2.10 (95% CI -2.50 to 6.70), standardized effect d = 0.30; z-test p = 0.371.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between N-acetylcysteine and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change in the NIMH Clinical Global Improvement Scale (CGI)

• 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:
  • N-acetylcysteine: mean -0.70 versus -1.10 on control; difference 0.40 (95% CI -0.38 to 1.18), standardized effect d = 0.33; z-test p = 0.314.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between N-acetylcysteine and the control. The interval gives the range of effects that remain compatible with the data.

The two posted secondary outcomes cover different aspects of reported symptoms and clinical change: parent-completed depression ratings and a clinical global improvement scale. Across both outcomes, the average changes were negative in each group, while the NAC-versus-combination mean differences were positive. Their confidence intervals include zero, so neither secondary comparison clearly distinguishes a between-group difference from no difference on the posted estimates.

The broad pattern is not a clear independent signal that overturns or resolves the primary result. Rather, the secondary outcomes are consistent with substantial uncertainty about comparative changes over the study period. They should be read alongside the primary P-YMRS result, not as substitutes for it. The measures are distinct, and a pattern in one scale need not match another because each captures a different domain or perspective.

Secondary outcomes usually carry less confirmatory weight when the registry does not report whether they were prespecified in a hierarchy, whether multiplicity was controlled, or which analyses were planned. Examining multiple outcomes can create more opportunities for chance findings. Here, the record lists the outcome measures but no reported analysis records. It also does not report an adjustment strategy for multiple comparisons.

For that reason, the secondary results are most useful as descriptive context and as a way to identify questions for further study. They should not be treated as conclusive evidence of a separate effect, nor should the direction of a group mean change be mistaken for a definitive treatment comparison. The registry does not provide a stated threshold for clinically important change on either secondary measure, further limiting judgments about the practical meaning of their estimated differences.

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

• Mean Change in the Parent-completed Children's Depression Inventory (CDI)
• Mean Change in the NIMH Clinical Global Improvement Scale (CGI)

9. Statistical Interpretation

10. Statistical Methods Explained

The posted results use group means and standard deviations for continuous outcomes. A mean is an average score or average change in a group. A standard deviation describes how dispersed individual observations are around that mean; it is not the uncertainty in the mean itself. In these results, the endpoint is a change score, so the group mean summarizes average movement from baseline to 6 weeks.

What does the mean difference represent?

The primary comparison is expressed as a mean difference, with the N-acetylcysteine group compared with the omega-3 fatty acid plus inositol group. The estimate is -2.6 P-YMRS units. A negative value means the average change in the NAC group was lower than the average change in the combination group. That direction is a mathematical description of the contrast, not a judgment about clinical importance. The scale’s interpretation matters: higher P-YMRS scores indicate more severe manic symptoms, and negative change indicates a decrease in score.

For a continuous outcome, a mean difference retains the outcome’s original units. This makes the estimate directly interpretable on the P-YMRS scale. It does not communicate the full distribution of individual changes, and it can be influenced by variability within groups. The standard deviations of 7.9 and 8.1 describe that variability in the posted primary results.

How should the confidence interval be read?

A confidence interval expresses the uncertainty around an estimated difference under the statistical procedure used to construct it. The primary interval runs from -7.756 to 2.556 units. Values within that range are compatible with the estimate at the stated confidence level, subject to the method’s assumptions. Since the interval includes zero, the results are compatible with no average difference as well as with differences favoring either direction. A confidence interval is not a guarantee that the true value falls in the range, nor does it assign probabilities to particular values without additional assumptions.

Interval width is informative about precision. A wider interval leaves more uncertainty about the magnitude of a contrast. It is possible for the point estimate to look substantial while uncertainty remains wide; the interval, rather than the point estimate alone, shows how firmly the data locate the difference. The registry does not report the model or exact interval construction method, so the interval should be interpreted as posted rather than attributed to a specific procedure.

What does the p-value add?

The primary p-value is unadjusted and equals 0.323. In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null and the analysis assumptions held. It does not measure the size or importance of an effect. It is not the probability that the null is true, and it does not establish the probability that a result will replicate. Because the registry does not report a full analysis specification, the exact test and assumptions underlying this p-value are not reported in the registry record.

The interval and p-value address related aspects of uncertainty, but they are not interchangeable with a decision about clinical meaning. The confidence interval gives a range of estimates compatible with the data under its construction; the p-value summarizes evidence against a particular null. Neither establishes equivalence. Demonstrating equivalence would require an explicitly stated equivalence margin and an analysis designed for that purpose, neither of which is reported in the registry record.

Why can spread matter?

General statistical explanation: when outcome values vary substantially within groups, the group means are less precise for a fixed amount of information. If a continuous outcome has more variability than a simple model assumes, a model that ignores that extra variability can understate uncertainty. This issue is often described as over-dispersion. The registry gives standard deviations for the posted outcomes, but it does not report an over-dispersion assessment or a model adjustment for it. It would therefore be inappropriate to assert that over-dispersion was present or that a particular correction was used.

The standard deviations are relatively large in relation to the mean changes for the primary endpoint, indicating that individual changes varied around the average. That observation does not reveal the shape of the outcome distribution or whether there were outliers. Individual-level data and distributional summaries are not reported in the registry record.

What can randomization and open-label conduct tell us?

In general, random allocation is intended to reduce systematic differences between groups at the point of assignment. It does not guarantee balance in a small trial, and it does not address every source of bias after allocation. Open-label conduct means treatment assignment was not masked according to the registry. For a parent-completed rating outcome, expectations or knowledge of treatment could potentially influence reporting; the registry does not quantify whether that occurred. These are design considerations, not proof that the observed results were biased.

The primary comparison is between active treatment strategies, with the combination of omega-3 fatty acids and inositol in one group and NAC in the other. It cannot separate the effect of omega-3 fatty acids from the effect of inositol, and it does not estimate either intervention against placebo. The registry does not report adherence, co-interventions, or analysis methods for missing outcome data. Such details would help assess how the randomized comparison was implemented and analyzed.

What analysis details remain unclear?

The record does not describe whether the analysis followed an intention-to-treat, per-protocol, or other population definition. It also does not specify how missing baseline or follow-up ratings were handled, whether covariates were included, or whether an analysis adjusted for baseline score. Those details are not reported in the registry record. The posted group summaries and comparisons can be interpreted descriptively, but the absence of these methodological details limits independent appraisal of the analysis.

The posted comparisons include unadjusted p-values. The registry does not report whether any multiplicity procedure was planned or applied. This matters particularly for secondary outcomes, because testing several outcomes can increase the chance of observing an apparently notable result by chance. The outcome-specific results should therefore be read in the context of the primary endpoint and the lack of a reported multiplicity plan.

11. Confidence Intervals and Precision

The primary mean difference is -2.6 P-YMRS units, with a 95% confidence interval from -7.756 to 2.556. The interval includes zero and spans negative and positive values. Thus, the posted estimate does not precisely identify whether the average change was lower or higher in the NAC group relative to the combination group, or how large a difference might be compatible with the data.

Precision is distinct from the point estimate. The estimate is the single best value reported by the comparison, while the interval communicates uncertainty around it. A broad interval can reflect limited information, outcome variability, or both; the registry record does not allow those contributions to be separated. The group standard deviations, 7.9 and 8.1, indicate spread in the primary outcome, while the group sizes reported for the outcome are 18 and 19. These features should be considered alongside the interval rather than treated as independent proof of a particular cause of imprecision.

The confidence interval does not establish equivalence. An interval that crosses zero can occur when the data are compatible with both no difference and potentially meaningful differences in either direction. The registry does not report a minimum clinically important difference or an equivalence margin for the P-YMRS, so it is not possible to judge the interval against a registry-stated threshold for clinical importance.

The secondary outcome comparisons also have intervals that include zero. Their precision does not resolve the uncertainty in the primary endpoint, and multiple outcome comparisons make isolated secondary findings less persuasive without a reported adjustment plan. Overall, the posted estimates are better viewed as uncertain comparative estimates than as precise measurements of a treatment difference.

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 sample-size planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. For these continuous outcome comparisons, the listed counts are participants per arm, not a combined total. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario sets the effect to detect as a stated fraction of the observed effect. The registry does not report the original protocol’s sample-size justification, target assumptions, or planning calculations; those details are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding planning number for a higher chance of detection under the same stated framework. These are prospective planning concepts, not descriptions of what happened in the completed trial.

The rows that use 100%, 75%, and 50% of the observed effect ask how planning requirements change if the effect to detect is smaller than the observed estimate. Smaller effects are harder to distinguish from random variation, so the calculation calls for more participants per arm. The progression is an illustration of that relationship, not evidence that any of those effects will occur in a future study.

The planning calculations are not observed power. Observed power is not a useful substitute for reading the estimate and its confidence interval after a trial. The interval and the uncertainty in the posted comparison are the more direct evidence about how precisely the trial estimated the difference.

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 = -2.600; pooled standard deviation σ = 8.003.
2. n = 2 × (1.96 + 0.842)² × 8.003² / -2.600² = 148.7, rounded up to 149 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 <- -2.6                      # observed difference in means
sigma <- 8.00348138535439                     # 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(3757585)
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 = 149 (80% power), 200 (90% power)
 75% of observed effect: n per arm = 265 (80% power), 355 (90% power)
 50% of observed effect: n per arm = 595 (80% power), 797 (90% power)
power.t.test: 149.7 
Simulated power at n = 149 per arm: 0.797 (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 a primary endpoint and two secondary endpoints, each assessed from baseline to 6 weeks. It does not report a plan for controlling multiplicity across these outcomes, such as a hierarchy of tests or an adjustment to account for multiple comparisons. That plan is not reported in the registry record.

Multiplicity matters because examining several outcomes can increase the chance of finding at least one result that appears unusual even when there is no underlying difference. This is a general statistical concern, not evidence that any particular posted result is a false positive. The secondary p-values are unadjusted, and their interpretation should remain exploratory unless a prespecified analysis plan indicates otherwise. The registry does not report such a plan.

There is also limited information about missing data. Although the outcome summaries list group sizes, the registry does not explain how participants with missing baseline or follow-up scores were handled, whether all randomized participants were included in each analysis, or whether any values were imputed. The analysis populations are not reported in the registry record. It is therefore not possible to determine from the posted results whether the estimates represent all randomized participants or a subset with available observations.

The record does not describe an intention-to-treat analysis, a per-protocol analysis, or another defined analysis population. It does not report the handling of withdrawals, adherence, treatment discontinuation, or changes in assigned treatment. These omissions do not show that a particular method was or was not used; they limit what can be established from the registry record.

The exact statistical model, covariate adjustment, assumptions, and sensitivity analyses are also not reported in the registry record. In the absence of those details, the posted means, standard deviations, confidence intervals, and unadjusted p-values can be described, but the analysis cannot be fully reconstructed or independently assessed from the record alone.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: depression (3.7%).

The registry reports serious adverse event figures for the two treatment groups. For omega-3 fatty acids plus inositol, 27 participants were listed as at risk, 0 as affected by a serious adverse event, and 11 as affected by other adverse events. For NAC, 27 were listed as at risk, 1 as affected by a serious adverse event, and 13 as affected by other adverse events. Deaths were recorded as 0 in both groups. The top serious-event term listed was depression, at 3.7%.

These are descriptive safety counts from the registry record. They do not by themselves establish whether an event was caused by treatment, and the record does not provide details about event timing, severity beyond the serious-event classification, or the relationship assessment for individual events. The listed at-risk counts are the registry’s denominators for these safety summaries; they should not be assumed to be the same as the group sizes reported for the primary outcome.

With only a small number of serious events recorded, the comparison is not precise evidence about relative safety. The absence of recorded deaths or serious events in a group does not establish that such events cannot occur. These figures describe what the registry reports for this trial and should not be generalized beyond its participants and follow-up.

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

The primary result describes average change in parent-rated manic-symptom scores over 6 weeks and the estimated difference between two active treatment strategies. It does not establish that either treatment caused the observed within-group changes, because the trial did not include a placebo group in the posted comparison. It also does not tell whether the two interventions differ from usual care.

The primary estimate is uncertain. Its confidence interval includes zero and values on either side, so the registry result is compatible with no average difference as well as with differences in either direction. This is not proof that the interventions are equivalent. Equivalence requires a defined margin and a design and analysis suited to that question; neither is reported in the registry record.

The endpoint captures one symptom domain using a parent-completed scale. It does not measure every feature of emotional dysregulation, and group averages cannot represent each participant’s experience. The record does not report a threshold for clinically important change, so a numerical change cannot be translated into a claim about meaningful improvement or deterioration from these data alone.

The study compared a combination of omega-3 fatty acids and inositol with NAC, using weight-based or age-based instructions described in the registry. The comparison cannot identify the separate contribution of omega-3 fatty acids or inositol. Open-label conduct also means participants and treatment providers were not masked according to the registry; the results do not quantify any influence that knowledge of assignment may have had on reporting or care.

These findings should be understood as estimates from this completed trial, in the population and follow-up period described in the registry. They do not establish effects for other populations, other durations, or other treatment regimens. The registry record does not report the detailed analysis plan, missing-data methods, or participant-level results needed for a fuller assessment of how robust the estimates are.

17. Why This Trial Matters Statistically

This trial raises several useful statistical questions for clinical researchers. The randomized, parallel design compares two active strategies, while the open-label conduct and parent-reported primary endpoint make it important to consider how outcome measurement and treatment awareness may affect interpretation. Those are design features to evaluate, not reasons to dismiss the estimates.

The central statistical feature is the gap between a point estimate and its precision. The posted primary mean difference is -2.6 P-YMRS units, but its confidence interval extends from -7.756 to 2.556 and includes zero. A reader who focuses only on the point estimate could overstate certainty; a reader who relies only on whether the interval crosses zero could overlook the range of differences still compatible with the data. Both the estimated magnitude and the uncertainty matter.

The trial also illustrates why outcome hierarchy and multiplicity plans are important. The registry identifies a primary endpoint and secondary outcomes, but it does not report an analysis plan for multiple comparisons. When several outcomes are assessed, prespecification helps distinguish confirmatory questions from exploratory ones and reduces the risk of giving undue weight to a chance finding.

Planning calculations based on observed effects can help illustrate how much information future studies might need under explicit assumptions. They do not recover the trial’s original planning rationale, which is not reported in the registry record, and they are not a substitute for a confidence interval. A future design would need assumptions about the effect worth detecting, outcome variability, analysis, and follow-up that are justified independently of the observed estimate.

Finally, the record demonstrates the value of reporting analysis populations, missing-data handling, model details, and safety methods alongside results. Without those details, readers can describe the posted estimates but cannot fully reconstruct how they were obtained or assess all relevant sources of uncertainty.

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.

Several limitations are specific to the information reported for this trial. The enrollment entry is 54, while the primary outcome summaries list group sizes of 18 and 19. The registry record does not explain the relationship between the enrollment figure and the outcome analysis sizes, including whether the difference reflects missing outcome data, exclusions, or another reason. It would be inappropriate to infer a cause from the posted record.

The trial was open-label, and its primary measure was completed by a parent. Awareness of treatment assignment could influence ratings or reporting in principle, but the registry does not measure such influence. The study also compared a combination intervention with NAC, so it cannot identify the separate effect of omega-3 fatty acids or inositol.

The follow-up period for the stated outcomes was 6 weeks. These results therefore do not address longer-term outcomes. Eligibility included youth with NVLD or ASD and current emotional dysregulation symptoms, but the registry does not provide detailed participant characteristics or separate results by condition, age, or other subgroups. The extent to which the posted averages represent particular subgroups cannot be assessed.

The registry does not report adherence, missing-data methods, analysis populations, the statistical model, or a multiplicity plan. It also does not report a threshold for clinically important change on the primary measure. These gaps limit assessment of the analysis and the clinical interpretation of the estimated differences. They are reporting limitations; the record does not establish that any particular method was omitted from the study itself.

The safety summaries are limited to the posted counts and do not provide event narratives or detailed attribution information. The small number of serious events also limits what can be concluded about comparative safety from this trial.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD) — NCT03757585.
• Registry record last updated 2025-06-05; status last verified 2025-06.
• Results first posted 2025-06-05.
• 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

NCT03757585 is a completed, randomized, open-label, parallel-group Phase 4 trial sponsored by Massachusetts General Hospital. It compared omega-3 fatty acids plus inositol with N-acetylcysteine in youth ages 5-17 years with NVLD or ASD and current emotional dysregulation symptoms. The registry lists enrollment as 54 and describes a 6-week study conducted via telepsychiatry.

The primary outcome was mean change in parent-completed P-YMRS score from baseline to 6 weeks. The posted mean difference for NAC relative to the combination group was -2.6 units, with a 95% confidence interval from -7.756 to 2.556 and an unadjusted p-value of 0.323. The interval includes zero, leaving uncertainty about the direction and size of the average difference.

Two secondary outcomes and safety summaries are also posted. The registry does not report the original sample-size rationale, detailed analysis plan, missing-data methods, analysis populations, or multiplicity handling. Those details are not reported in the registry record.