KET-RO Plus RO DBT for Treatment Resistant Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for KET-RO Plus RO DBT for Treatment Resistant Depression (NCT06138691), a non-randomized phase 1 study. The primary outcome is Decrease in Depressive Symptoms.

2. Clinical Question

The study was framed as a pilot assessing safety and feasibility, as well as developing methodological approaches related to precision medicine. Its single-group design can describe observations among participants receiving the combined intervention, but it cannot provide a randomized comparison with an untreated group or another therapy. The listed secondary measures cover depressive and anxiety symptoms, reward positivity, error-related negativity, social connectedness, and loneliness. Numerical results for these measures are not reported in the registry record.

3. Trial Design

This was a Phase 1, completed, non-randomized study with a single-group model and no masking. The registry lists enrollment of 16 and identifies Washington University School of Medicine as the sponsor. The study start date was 2023-10-04, and primary completion was 2025-01-11. These record details describe the study’s registration and status; they do not establish how participants were recruited or how treatment was delivered.

All participants were assigned to the combined ketamine infusion and RO DBT intervention in the study’s single-group structure. There was no randomized allocation, masked assessment, or separate control arm reported. Consequently, an observed change over time, if available, would describe the participants’ experience during the study, not a treatment contrast against a concurrent control group. Other influences on change cannot be separated from the intervention using this design alone.

The record states that 16 participants consented, while 3 were ineligible at baseline and did not complete any ketamine or RO DBT treatment. The adverse-event results list 13 participants at risk. The record does not describe the analysis population used for the primary endpoint, whether all eligible participants completed follow-up, or how missing observations were handled. It also does not report a detailed schedule of intervention sessions or assessment visits beyond the primary outcome timeframe of approximately 5 months.

The stated aims included evaluating safety and feasibility in young adults with treatment-resistant depression and exploring methodological approaches for precision medicine. Specific feasibility criteria and results are not reported in the registry record. The study is marked completed, but completion status alone does not supply numerical outcome findings or indicate whether every planned assessment was completed.

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: 16 participants were consented and enrolled. However, 3 participants were deemed ineligible at the baseline assessment and did not start treatment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 16 participants consented to the study. However, 3 were ineligible at baseline and so did not complete any ketamine or RO DBT treatment.

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 Decrease in Depressive Symptoms, measured over Approximately 5 months.

The primary endpoint was a decrease in depressive symptoms assessed using the Montgomery and Asberg Depression Rating Scale (MADRS), a clinician-interviewed assessment. The registry describes a score range from 0-60 and states that higher scores indicate greater depression severity. The outcome is identified as a continuous measure summarized by a mean and standard deviation, with an assessment timeframe of approximately 5 months.

A clinician-interviewed scale provides a structured way to assess symptom severity. In general, repeated scores can be used to describe whether the measured symptom level changes over time. The direction of interpretation for this scale is specified in the registry: higher scores represent greater severity. The endpoint title refers to a decrease, but the registry record does not give the numerical change, baseline or follow-up means, standard deviations, or an uncertainty interval. It therefore does not show the size or precision of any change in MADRS scores.

The record also does not describe how the decrease was calculated, the exact assessment visits included, or the primary analysis population. Those details matter for interpreting a change score, especially when participants do not all contribute observations at each assessment. They are not reported in the registry record. The endpoint identifies what the study intended to measure, but it is not itself evidence of an observed decrease.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is identified as a continuous measure summarized using a mean and standard deviation. In general, a mean describes the central level of a set of observations. A standard deviation describes how spread out individual observations are around that mean. The two quantities answer different questions: the mean concerns the average score, while the standard deviation concerns variation among scores. Neither is reported numerically for the primary outcome in the registry record, so the average level and variability cannot be assessed.

The registry describes MADRS scores as ranging from 0-60, with higher scores indicating greater depression severity. In general, a decrease in the mean score over time would describe a lower average score at the later measurement, while the amount of decrease would be needed to judge its magnitude. The record does not report the numerical scores or specify the exact calculation used for the decrease. No change estimate can therefore be reconstructed from the registry record.

How should uncertainty be understood?

In general, a confidence interval gives a range of values that are compatible with the data and the assumptions of the statistical method. It communicates precision as well as the estimate’s direction and size. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. No confidence interval for the primary outcome is reported in the registry record. Without an estimate and its uncertainty, the numerical size and precision of any change cannot be evaluated.

A p-value, when reported, describes how unusual the observed data would be under a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, nor does it express the size or clinical importance of an effect. The registry record does not report a primary-outcome p-value or a specified hypothesis test. Statistical significance therefore cannot be assessed from the recorded information.

What does the single-group design allow?

The trial is listed as non-randomized and single-group, with no masking. In general, a single-group study can describe outcomes among participants observed during a study, but without a concurrent comparison group it cannot estimate a randomized treatment contrast. A before-and-after change may coincide with the intervention, but this design cannot distinguish the intervention’s contribution from other influences on change. Lack of masking can also matter in general when outcome assessment involves judgment or participant report, although the record does not describe how assessments were conducted beyond identifying MADRS as clinician-interviewed.

Randomization, when used, helps make groups comparable on measured and unmeasured characteristics on average. This study did not use randomized allocation, and there was no separate control group. No adjustment strategy for confounding is reported in the registry record. The study’s design should therefore be interpreted as a pilot, not as a controlled estimate of comparative effectiveness.

What can be learned from the safety counts?

The registry lists 13 participants at risk for serious adverse events and 0 serious adverse events; it also lists 13 at risk and 0 other adverse events, and 0 deaths. These are descriptive counts. In general, a zero count in a study does not prove that an event is impossible or that risk is absent. The amount of information from a safety count depends on the number observed, the duration and completeness of observation, and how events were defined and collected. Details on those points are not reported in the registry record.

How should planning illustrations be read?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, planning quantities are expressed as participants per arm for 80% or 90% power; time-to-event quantities are described as total events. The primary outcome is continuous, not time-to-event.

These assumptions describe hypothetical planning calculations, not the trial’s original design or observed statistical power. The registry record does not report the numerical observed effect or the numerical planning estimates, and it does not report the trial’s own sample-size justification. A planning illustration based on an observed effect is conditional on that effect estimate; it does not establish that the trial had a particular probability of detecting a true effect.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model understates variability, uncertainty estimates may be too narrow and statistical tests may appear more decisive than warranted. This concept is relevant to statistical interpretation broadly, but the registry record does not report a model for the primary outcome or indicate that over-dispersion was assessed. It should not be inferred that over-dispersion was present or that a particular correction was used.

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("Ketamine and RO DBT")
n   <- c(13)
m   <- c(12.13)
sp  <- c(8.69)
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  Ketamine and RO DBT  13  12.130  8.690  6.879  17.381

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome of depressive symptoms and secondary outcomes covering depressive and anxiety symptoms, reward positivity, error-related negativity, social connectedness, and loneliness. It reports 8 outcome measures and 9 analyses. The record does not describe how those outcomes and analyses were organized into a prespecified testing hierarchy, whether any tests were designated exploratory, or whether adjustments for multiple comparisons were planned or applied. Those multiplicity procedures are not reported in the registry record.

In general, when many statistical hypotheses are tested, the chance of at least one apparently notable finding can increase unless the analysis plan accounts for the number and relationship of tests. Adjustment methods can change the interpretation of p-values and confidence intervals. The registry does not provide sufficient information to determine whether such methods were used. Numerical results for the listed secondary measures are also not reported in the registry record, so their estimates and uncertainty cannot be assessed.

Missing-data handling is not reported in the registry record. It does not state how many participants completed each assessment, whether the primary outcome was analyzed only among participants with observed measurements, or whether an imputation or other method was used. The record notes that 3 of the 16 people who consented were ineligible at baseline and did not receive treatment, and lists 13 participants at risk for adverse events. It does not establish the endpoint analysis population or follow-up completeness.

In general, missing data can affect an estimate when the likelihood of missingness is related to participants’ outcomes or characteristics. The assumptions and methods used to address missing observations therefore matter. With no reported analysis population, missing-data procedure, or endpoint results, the primary outcome cannot be independently evaluated for these issues.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry lists one group, “Ketamine + RO DBT.” For serious adverse events, 13 participants were at risk and 0 were affected. For other adverse events, 13 were at risk and 0 were affected. The death count was 0. No serious adverse-event terms are listed.

These figures are counts recorded for the study, not proof that the combined intervention carries no risk. In general, a zero count means that no events of the specified type were recorded in the stated risk set; it does not rule out events that are uncommon, occur later, or were not captured under the study’s recording procedures. The registry record does not report detailed definitions, observation duration for safety, collection procedures, or event-level descriptions. It also does not provide a separate comparison group, so the safety counts cannot be contrasted with a control group within this trial.

The record’s safety denominator should be kept distinct from the consent count. It states that 16 participants consented, 3 were ineligible at baseline and did not complete treatment, and 13 were at risk in the adverse-event listing. The record does not specify the primary outcome analysis population. These safety figures should therefore be read narrowly as the recorded adverse-event counts and denominators, rather than as a full account of all possible safety outcomes.

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

The registry record documents a completed Phase 1 pilot with a single-group design and a stated primary outcome: decrease in depressive symptoms measured with MADRS at approximately 5 months. It also gives a study enrollment of 16, describes baseline ineligibility for 3 participants, and reports safety counts for a risk set of 13. These details establish the study’s registered structure and some descriptive safety information.

The record does not report the numerical primary outcome results. It therefore does not indicate the average MADRS change, its variability, or the precision of an estimate. It also does not report numerical results for the secondary outcomes. The outcome title alone cannot be treated as evidence that a particular decrease occurred, and no quantitative conclusion about symptom change can be drawn from the information recorded.

Even if numerical before-and-after results were available, the absence of a randomized comparison group would limit causal interpretation. In general, a single-group change cannot distinguish an intervention effect from other influences that may occur over time. The non-randomized and unmasked design should be considered when interpreting any outcome estimates if they are reported elsewhere.

The safety listing records 0 serious adverse events, 0 other adverse events, and 0 deaths among the stated risk set. These observations do not demonstrate that adverse events are impossible or that safety has been established for other people or settings. The record does not give detailed event definitions or duration of safety observation.

Accordingly, the registry record supports a description of the trial’s aims, design, outcome measures, participant flow details, and listed adverse-event counts. It does not provide enough numerical outcome information to quantify changes in depressive symptoms, assess their precision, or make a controlled comparison.

14. Why This Trial Matters Statistically

This trial is statistically notable as a pilot with an explicitly limited structure: non-randomized allocation, no masking, and a single group. Those features make clear why design and interpretation must be considered together. The study can be described in terms of its registered aims and measures, but its structure does not create a randomized comparison of the combined intervention against another condition.

The registry names a clinician-interviewed continuous primary outcome and several secondary measures spanning symptoms, neural measures, and social experience. That breadth makes transparent reporting of analysis populations, missing data, and multiplicity especially important. The record lists 8 outcome measures and 9 analyses, but does not report how analyses were prespecified or whether multiplicity procedures were used. Numerical results for the outcome measures are not reported in the registry record.

The record also distinguishes the total number who consented from the number in the adverse-event risk set. It says 16 participants consented, 3 were ineligible at baseline and did not complete treatment, and 13 were at risk in the safety listing. Clear accounting of participant flow is important for understanding who contributed to each estimate. The primary endpoint analysis population and follow-up completeness are not reported.

Finally, the record includes planning assumptions for illustrative sample-size calculations but does not report numerical planning estimates or the trial’s own sample-size justification. General planning calculations should not be confused with observed power or treated as evidence about the results. The study’s statistical importance lies in the questions it sets up and the design constraints that shape interpretation; the record does not supply the numerical outcome findings needed for an estimate of change.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this study are apparent from the registry record. The trial used a single-group, non-randomized design with no masking and no separate control group. As a result, the record cannot support a randomized comparison between the combined intervention and another treatment or control condition. Any change over time, if reported, would need to be interpreted in light of that design.

The enrollment was 16, while the record states that 3 participants were ineligible at baseline and did not complete treatment. The adverse-event listing uses a risk set of 13, but the record does not report the analysis population for the primary endpoint or explain whether any additional participants lacked follow-up data. Methods for handling missing outcome observations are not reported in the registry record.

The numerical results for the MADRS primary outcome and the listed secondary measures are not reported in the registry record. Consequently, estimates, variability, confidence intervals, and test results cannot be evaluated. The record lists 8 outcome measures and 9 analyses but does not describe multiplicity handling or the status of analyses as confirmatory or exploratory.

The registry identifies the intervention as intravenous ketamine combined with RO DBT, but detailed delivery information is not reported in the registry record. The record also does not report specific feasibility criteria, the primary endpoint analysis method, or the trial’s sample-size justification. Safety counts are available, but detailed event definitions, collection procedures, and observation duration are not reported. These omissions limit the detail with which the study’s methods and findings can be assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: KET-RO Plus RO DBT for Treatment Resistant Depression — NCT06138691.
• Registry record last updated 2026-03-30; status last verified 2026-03.
• Results first posted 2026-03-30.
• 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

NCT06138691 is a completed Phase 1, non-randomized, unmasked, single-group pilot sponsored by Washington University School of Medicine. The registered intervention combined ketamine infusion with Radically Open Dialectical Behavior Therapy. The study concerned treatment-resistant depression, and its summary described young adults; the official title specified adults with moderate to severe depression.

The registry reports enrollment of 16. It states that 3 participants were ineligible at baseline and did not complete treatment. The primary outcome was a decrease in MADRS depressive symptom scores at approximately 5 months. Listed secondary measures included symptom ratings, reward positivity, error-related negativity, social connectedness, and loneliness.

The record does not report numerical primary or secondary outcome results, the endpoint analysis population, or missing-data and multiplicity procedures. The adverse-event listing reports 0 serious adverse events and 0 other adverse events among 13 at risk, and 0 deaths. These descriptive figures do not establish absence of risk or provide a controlled safety comparison.