Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease (NCT04552795), a na phase 1, phase 2 study. The primary outcome is Change in Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants.

2. Clinical Question

The study’s stated objective was to examine whether 3TC could engage its intended target and reach the central nervous system, while also assessing Alzheimer disease-relevant outcomes and safety and tolerability. The registry describes the primary endpoint as change in reverse transcriptase activity in plasma from baseline to 24 weeks. It also lists change in dementia severity based on the PACC-5 Z-score and incidences of treatment-emergent adverse events and abnormal vital signs as secondary outcomes.

These questions are framed as an early investigation, not as a comparison of 3TC with another treatment or with a control condition. With a single group, the posted design can describe changes over time among participants, but it cannot isolate treatment-associated change from other explanations such as natural fluctuation, changes in measurement, or concurrent influences. The record’s stated focus on safety and feasibility, target engagement, and initial outcome data is consistent with a pilot study. The registry does not report a numerical primary endpoint result, so the posted record does not establish the direction or size of change in reverse transcriptase activity.

3. Trial Design

This completed study is listed as Phase 1 and Phase 2 and enrolled 12 participants with early-onset Alzheimer disease. The intervention was 3TC, identified in the registry as a drug. The arm description specifies open-label administration of 300-mg daily for 24 weeks. The study is classified as a single-group model, with allocation listed as NA and masking listed as none. No separate comparison arm is described.

In a single-group open-label design, participants receive the study intervention and outcomes can be observed over time. Because there is no concurrent control group, a change between baseline and follow-up is not a controlled estimate of how outcomes would differ without the intervention. Open-label status also means that the registry does not describe masking of participants or study personnel. These design features are important when interpreting changes in clinical measures and reported adverse events.

The record lists the study status as completed, with a start date of 2021-02-15 and a primary completion date of 2023-05-04. These dates describe the registry timeline; they do not supply missing outcome results. The study’s brief summary describes goals that include target engagement, central nervous system penetration, suppression of neurodegeneration, and safety and tolerability. The listed primary endpoint specifically concerns plasma reverse transcriptase activity, while listed secondary outcomes include dementia severity based on the PACC-5 Z-score and adverse events and vital signs.

The registry record does not report a sample-size justification, a detailed statistical analysis plan, or an explanation of how the study phase labels relate to its objectives. It also does not describe an allocation procedure beyond listing allocation as NA. The design should therefore be read from the features actually recorded: a completed, open-label, single-group study of 3TC in 12 participants, followed for 24 weeks as described in the arm information. The registry’s outcome listing alone is not evidence that each listed measure has a posted numerical result.

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

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 Reverse Transcriptase Activity From Baseline to 24 Weeks in Plasma of Study Participants, measured over Baseline to 24 weeks.

The primary endpoint is change in reverse transcriptase activity in plasma from baseline to 24 weeks, expressed in enzyme units. The registry describes measurement using a modified version of the EnzCheck Reverse Transcriptase assay. The stated purpose is to assess target engagement: whether the intervention is associated with a measurable change in the activity of the intended target.

Target engagement is a mechanistic question. It asks whether a biological measure relevant to the proposed target changes after exposure to the intervention. Such a measure can help characterize biological activity, but it is not, by itself, a measure of clinical benefit. The registry’s brief summary also mentions central nervous system penetration and suppression of neurodegeneration as objectives, but the primary endpoint named in the record is plasma reverse transcriptase activity. A plasma measure should not be treated as a direct demonstration of what occurred in the central nervous system unless the record reports evidence supporting that interpretation.

The endpoint is continuous, and the registry identifies the summary parameter as a mean with standard error as the dispersion measure. A mean summarizes the group’s average observed change; a standard error describes the statistical precision of that estimated mean, rather than the spread of individual measurements. The posted registry record does not include the primary endpoint’s numerical result, standard error, confidence interval, or analysis count. Consequently, the endpoint’s direction, magnitude, and precision cannot be assessed from the registry information. Its planned role can be explained, but the record does not permit a quantitative conclusion about target engagement.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information available in the registry is limited. It identifies a continuous primary outcome summarized by a mean and standard error, gives a baseline-to-24-weeks timeframe, and describes a modified assay. It also identifies the study as open-label and single-group. The record does not report a detailed statistical analysis plan, so the explanations below distinguish general statistical concepts from methods specifically documented for this study.

What does a mean represent?

General statistical explanation: A mean is an average across the observations included in an analysis. For a continuous outcome such as enzyme activity, it can summarize the group’s central value or average change. An average can make a group-level pattern easier to describe, but it does not show how much individual participants vary. Different participants may have changes that are quite different from the mean. The registry’s designation of the primary parameter as MEAN indicates the intended summary type, but the numerical mean is not reported in the registry record.

What does a standard error describe?

General statistical explanation: A standard error describes the precision of an estimated quantity, such as a mean. It is not the same as the standard deviation, which describes variability among individual observations. A smaller standard error generally indicates a more precise estimate under the analysis assumptions, while a larger one indicates greater uncertainty. A standard error alone does not show the range of individual responses. Here, standard error is listed as the dispersion measure for the primary endpoint, but neither its value nor a confidence interval is reported in the registry record.

How is a confidence interval useful?

General statistical explanation: A confidence interval presents a range of values compatible with an estimate under a specified statistical procedure. It helps readers assess precision and the range of effects consistent with the data, rather than relying on a single point estimate. Its interpretation depends on the analysis and assumptions used. No confidence interval for the primary endpoint is reported in the registry record. Without the estimate and interval, the numerical size and uncertainty of the primary result cannot be evaluated.

What does the single-group structure imply?

General statistical explanation: A baseline-to-follow-up analysis in one group can summarize how the measured outcome changes over time among observed participants. It cannot by itself distinguish intervention-associated change from temporal change, measurement variability, or other influences. A concurrent comparison group can help address some of those issues, but this record describes no such group. The registry lists allocation as NA and the model as SINGLE GROUP. Thus, a change over time, if reported elsewhere, would not automatically be a randomized treatment effect.

Why does open-label status matter?

General statistical explanation: When participants and study personnel know the intervention being given, expectations and knowledge of treatment can affect some aspects of measurement, reporting, or clinical assessment. The possible relevance depends on the outcome. A laboratory assay may have different sources of measurement variability from a subjective assessment, but assay handling and analysis procedures still matter. The record lists masking as none. It does not describe procedures that would permit a more detailed assessment of these potential influences.

What is over-dispersion?

General statistical explanation: Over-dispersion occurs when the observed variability in data is greater than a statistical model assumes. If ignored, uncertainty estimates can be too small and statistical conclusions can appear more precise than warranted. This issue is especially relevant to certain count or event models; it is not a fact established about this study. The registry entries do not report an over-dispersion assessment or a model used for the primary outcome. The primary measure is described as continuous and summarized by a mean, so readers should not assume a particular model or adjustment.

What are planning sample-size illustrations?

General statistical explanation: A sample-size illustration asks how many participants might be needed under stated assumptions to detect a specified effect with a specified testing procedure. It is a planning exercise, not a statement of what the enrolled study could reliably detect after the fact. The planning assumptions recorded specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The described illustrations use a fraction of an observed effect. They are not the documented design for this single-group study, and they must not be described as observed power.

The registry record does not report the study’s own sample-size justification, the analysis population, the handling of missing observations, or whether any interim analyses were planned. Those omissions prevent a full appraisal of how the analysis was intended to address precision, incomplete follow-up, or multiple outcomes. The posted endpoint description and design classification support a limited account of the planned measurement, not a reconstruction of unreported methods.

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("Open-Label 3TC")
n   <- c(12)
m   <- c(-0.0074)
sp  <- c(0.03)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Open-Label 3TC  12  -0.007  0.104  -0.073  0.059

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, but the record does not report a detailed statistical analysis plan for controlling or otherwise addressing multiplicity. When several outcomes are examined, the chance of finding at least one apparently notable result can depend on how many analyses are conducted and how they are interpreted. General statistical explanation: A prespecified primary outcome can help focus interpretation, while secondary outcomes often provide supporting or exploratory information. The registry’s outcome listing alone does not tell readers what testing hierarchy, adjustment, or interpretation rules were planned.

The record identifies five outcome measures and zero analyses. This does not establish that all outcomes were analyzed, nor that no analyses were conducted outside the posted registry entry. The numerical primary outcome and corresponding uncertainty are not reported in the registry record. Numerical results for the listed secondary outcomes are also not included in the registry record.

Missing-data methods and analysis populations are not reported in the registry record. The record does not say how participants with incomplete follow-up were handled, whether all enrolled participants were included in each outcome analysis, or what rules defined an evaluable observation. This matters because the observed set can differ from the enrolled group, and the way incomplete measurements are handled can affect estimates and uncertainty. No particular method should be assumed.

For these reasons, the available information does not allow assessment of the multiplicity strategy, the impact of missing measurements, or the exact population contributing to any outcome analysis. Those details would be needed to evaluate the analysis beyond the design and outcome descriptions posted in the registry.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal bleeding (8.3%).

The registry’s safety figures are listed for the Open-Label 3TC group. It reports 12 participants at risk for serious adverse events, with one affected; 12 at risk for other adverse events, with two affected; and zero deaths. Gastrointestinal bleeding is listed as the top serious adverse event term, at 8.3%.

These are descriptive counts from a single-group study. They do not compare event rates with a control group, because the registry describes no separate comparator. The figures alone do not establish whether an event was caused by 3TC, whether it was expected, or how its timing related to treatment. The term “serious adverse event” is a classification and should not be treated as synonymous with an event caused by the intervention.

The serious-event count and the named gastrointestinal bleeding term convey different kinds of information: one is a count of participants affected by serious events, while the other is a listed event term with a percentage. The registry information does not provide event-level details, severity descriptions beyond the serious classification, or a causal assessment. Nor does the record establish from these figures alone how the safety profile compares with another treatment or with no intervention. The counts should therefore be read as a limited description of reported safety in this study, not as a comparative or causal estimate.

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

The study addresses an early research question: whether 3TC can engage its intended target, alongside investigation of safety, tolerability, and Alzheimer disease-relevant measures. Its primary endpoint is a biological measure of plasma reverse transcriptase activity from baseline to 24 weeks. That choice is relevant to the stated target-engagement objective, but the registry record does not report the numerical endpoint result. Consequently, this record does not show the size, direction, or precision of any observed change in that measure.

Even if a baseline-to-follow-up change were available, a single-group open-label design would not establish that the intervention caused the change. Without a control group, other explanations for change cannot be separated using a randomized comparison. The study’s enrollment of 12 and its pilot framing also mean that the record should be read as an initial investigation rather than a definitive comparative evaluation. This description concerns the design and evidence available in the registry, not a judgment about clinical use.

The safety information is similarly bounded. The record lists one participant affected by a serious adverse event, two affected by other adverse events, zero deaths, and gastrointestinal bleeding as the top serious adverse event term at 8.3%. These are reported observations, not evidence on their own about causation or comparative risk. The registry does not provide the detailed context needed to interpret each event.

The record does not establish clinical effectiveness, demonstrate suppression of neurodegeneration, or confirm central nervous system penetration. Although those aims appear in the study summary, they are not numerical findings in the registry record. The PACC-5 Z-score is listed as a secondary outcome, but no result is reported. The most defensible reading is that this completed pilot was designed to collect initial biological, clinical, and safety information, while the posted record does not contain the primary numerical result needed to quantify target engagement.

14. Why This Trial Matters Statistically

This study illustrates a distinction that matters in biostatistics: a clearly stated biological objective is not the same as a reported quantitative finding. The registry identifies target engagement as a central purpose and names a measurable primary endpoint, but the numerical result is not reported in the registry record. Naming a measure helps clarify what investigators intended to assess; it does not allow readers to infer whether the measure changed or by how much.

The design also makes the role of comparison explicit. A single-group study can describe outcomes among participants receiving the intervention, but it does not provide a concurrent control for interpreting change over time. Open-label administration is another feature readers should consider when assessing outcome measurement and reporting. Neither feature makes descriptive observations unusable, but both limit the kind of causal comparison that can be drawn from them.

The registry’s safety counts show why denominators and outcome definitions matter. Counts are easier to interpret when readers know how many participants were at risk and which event classification is being summarized. Yet even with those details, a single-group count does not provide a comparative risk estimate or establish causation. The gastrointestinal bleeding entry adds a named term, but it does not replace the broader context of event timing, assessment, and attribution.

Finally, planning calculations and observed findings answer different questions. Sample-size illustrations can show how assumptions about an effect and analysis relate to hypothetical design requirements. They cannot fill in an unreported outcome or be interpreted as observed power. Keeping these distinctions clear helps readers avoid overstating what a small pilot registry entry can establish while still recognizing its role in describing an early research program.

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 principal limitation for interpreting this record is that the primary endpoint’s numerical result is not reported in the registry record. Without the estimate and its uncertainty, readers cannot assess the observed direction, size, or precision of change in plasma reverse transcriptase activity. The registry lists outcome measures and analyses counts, but those entries do not supply the missing result.

The study is described as open-label and single-group, with no separate comparator. As a result, the design does not support a randomized comparison of outcomes with and without 3TC. Any change between baseline and follow-up, if available elsewhere, could reflect influences beyond the intervention. The enrollment of 12 also means that estimates from this pilot would be based on a limited group of participants; the record does not report a sample-size justification that would explain the intended precision.

The registry record does not report details needed to evaluate how the endpoint was analyzed, which participants contributed to each analysis, how missing measurements were handled, or what multiplicity approach was planned. It does not provide a detailed analysis plan or interim-analysis information. These omissions make it difficult to assess whether the analysis followed prespecified procedures or how uncertainty and incomplete data were addressed.

The safety figures are limited to the posted group-level counts and a top serious adverse event term. The information does not include event-level context, timing, or a causal assessment. The listed objectives include central nervous system penetration and suppression of neurodegeneration, but the record details do not provide results establishing those outcomes. The PACC-5 outcome is listed without a numerical finding. These limitations concern what can be concluded from the registry information, not necessarily what may exist in other records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Study to Investigate the Safety and Feasibility of AntiRetroviral Therapy for Alzheimer's Disease — NCT04552795.
• Registry record last updated 2024-08-09; status last verified 2024-07.
• Results first posted 2024-08-09.
• 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 NCT04552795, a completed Phase 1 and Phase 2, open-label, single-group pilot study of 3TC in early-onset Alzheimer disease. Enrollment was 12, and the arm description specifies 300-mg daily for 24 weeks. The primary endpoint is change in plasma reverse transcriptase activity from baseline to 24 weeks, summarized as a mean with standard error. The numerical primary outcome is not reported in the registry record.

Listed secondary outcomes include change in dementia severity based on the PACC-5 Z-score, treatment-emergent adverse events, and abnormal vital signs. The record reports one participant affected by a serious adverse event, two affected by other adverse events, zero deaths, and gastrointestinal bleeding as the top serious adverse event term at 8.3%. Because there is no comparator group, these are descriptive rather than comparative safety findings. The record does not report a detailed statistical analysis plan, sample-size justification, missing-data approach, or analysis populations.