This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes (NCT04262479), a na phase 2 study. The primary outcome is Injection Site Skin Reactions.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04262479 |
| Phase | Phase 2 |
| Condition | Latent Autoimmune Diabetes in Adults |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 14 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Norwegian University of Science and Technology |
| Results posted | Yes |
2. Clinical Question
Population
Adults with latent autoimmune diabetes in adults (LADA) were eligible for the study. The registry record reports an enrollment of 14 participants. It does not provide further eligibility details in the record, such as diagnostic criteria, disease duration, or baseline characteristics.
Intervention
The study evaluated intra-inguinal lymph-node injections of GAD-alum together with oral vitamin D supplementation. The arm description specifies 3 injections of 4 µg GAD-alum, with injections one month apart, and vitamin D from one month before the first injection until one month after the third injection, for 120 days in total.
Comparator
There was no separate comparison arm in the registry design. The study is listed as single group, with allocation recorded as NA and masking as none. Consequently, the registry record does not offer a concurrent untreated or alternative-treatment group for comparing outcomes.
Primary question
The primary outcome concerns injection-site skin reactions one hour after an injection. The registry defines these as erythema, oedema, haematoa, tenderness, pain, itching, or another finding. The record does not report the numerical result for this endpoint, so the frequency of reactions cannot be characterized from the posted results.
3. Trial Design
This completed phase 2 study was registered as a pilot study of safety, feasibility, and insulin-promotion in people with LADA. It enrolled 14 participants. The recorded study dates are 2020-03-02 for the start and 2022-05-05 for primary completion. The sponsor was Norwegian University of Science and Technology.
The registry describes one study group receiving GAD vaccination with vitamin D supplementation. Each participant was to receive 3 injections of 4 µg GAD-alum, one month apart. Vitamin D was scheduled from one month before the first injection until one month after the third injection, for 120 days in total. The intervention listing names recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel, and Vitamin D.
The design is single group, allocation is listed as NA, and masking is listed as none. This is not a randomized comparison, and there is no like-for-like control arm. Outcomes in the treated group therefore describe what was recorded during this study, but do not by themselves distinguish treatment-related change from the natural course of the condition, background care, or other influences.
The primary outcome is injection-site skin reactions one hour after injection. Secondary outcomes include insulin secretion change from baseline at 5 months and 12 months, change in HbA1c, fasting glucose and fasting C-peptide, and change in maximum C-peptide during a mixed meal tolerance test. The registry lists 12 outcome measures and 10 analyses, but does not report a statistical analysis plan or explain how those outcomes and analyses relate to one another.
The registry record does not report the study's sample-size justification, interim analyses, detailed eligibility criteria, or a statistical plan. Those details should not be inferred from the pilot designation or the enrollment count.
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
| Stage | GAD-vaccination With Vitamin D Suppletion |
|---|---|
| STARTED | 14 |
| COMPLETED | 14 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All study participants received 3 injections of 4 µg GAD-alum.
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.
| Characteristic | Unit | GAD-vaccination With Vitamin D Suppletion |
|---|---|---|
| Participants analysed | 14 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 46 (30 to 62) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 7 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Sweden | participants | 8 |
| Region of Enrollment: Norway | participants | 6 |
| Time from diagnosis to inclusion, months | months | 4 (3 to 15) |
| BMI, kg/m^2 | kg/m^2 | 25.1 (19.2 to 36.7) |
| Fasting C-peptide, nmol/L | nmol/L | 0.55 (0.25 to 1.35) |
| Fasting glucose, mmol/L | mmol/L | 6.7 (4.8 to 12.5) |
| HbA1c, mmol/mol | mmol/mol | 42 (35 to 65) |
6. Primary Endpoint
The registry lists the primary outcome as Injection Site Skin Reactions, measured over 1 hour.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of injection-site skin-reaction events recorded one hour after injection. The listed findings include erythema, oedema, haematoa, tenderness, pain, itching, or another finding. The endpoint is therefore focused on reactions at the injection site within a defined short observation period, rather than on insulin secretion or longer-term metabolic change.
As a general endpoint rationale, recording local reactions can help characterize immediate tolerability and the practical feasibility of an injection procedure. A count of events, however, is not automatically the same as a count of affected participants: one participant may have more than one event, depending on the outcome definition and analysis. The registry record does not clarify whether events were counted per injection, per participant, or using another aggregation rule.
The posted registry record does not report the numerical result for this primary endpoint. It also does not give a distribution, uncertainty interval, or detailed analysis method for the reaction count. As a result, the endpoint's observed frequency and precision cannot be evaluated from the reported information. The listed timeframe is one hour, so the endpoint description alone should not be interpreted as a complete account of reactions occurring at other times.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a completed, single-group phase 2 pilot study with an enrollment of 14 participants. Its primary endpoint is injection-site skin reactions one hour after injection. However, the posted results described in the registry record do not include a numerical result for that endpoint. Thus, the record does not permit an estimate of how often the listed reactions occurred, nor does it show the uncertainty around such an estimate.
The study also lists outcomes related to insulin secretion, HbA1c, fasting glucose, and C-peptide. The registry record does not report numerical results for these outcomes in the information available for this analysis. The study's stated interest in preservation of endogenous insulin production is a study objective, not evidence that a particular change was observed. Without outcome estimates and their uncertainty, the direction, magnitude, and precision of any changes cannot be assessed.
The safety summary reports 2 participants at risk with serious adverse events among 14 at risk, and 12 participants at risk with other adverse events among 14 at risk. The registry lists “Angina unstable” and “Muscle rupture” among the top serious terms, each at 7.1%. It reports 0 deaths. These entries describe the safety information recorded for the study; they do not establish that an event was caused by the intervention. The registry information does not include the case-level details or an attribution assessment needed to interpret individual events fully.
Because the study has no separate control group and is unmasked, observed changes cannot be compared with outcomes under a concurrent alternative. This matters especially for outcomes that can vary over time or be influenced by other aspects of care. A within-group change, if reported, would describe change during follow-up, but would not isolate the effect of the study intervention.
The registry lists 12 outcome measures and 10 analyses. It does not describe how the analyses were selected, whether they were prespecified, or how uncertainty and multiple outcomes were handled. Those omissions limit interpretation of any result that might be reported elsewhere. The record also does not provide the analysis population or a detailed account of missing outcome data.
Overall, the registry information characterizes the study design, treatment schedule, primary endpoint, and a limited set of safety counts. It does not provide the primary endpoint result or numerical findings for the listed metabolic outcomes. The available information therefore supports a description of what the study set out to evaluate and what safety counts were recorded, but not a conclusion about the magnitude or precision of treatment-related changes.
9. Statistical Methods Explained
Several statistical ideas help frame the registry record, while remaining distinct from claims about methods the investigators actually used. The record describes a single-group study with no masking and no allocation to a comparator. It does not report a statistical analysis plan. Accordingly, the explanations below describe general principles, not a reconstruction of the study's unreported methods.
What does a single-group design allow?
In a single-group study, outcomes can be described for the participants who received the study intervention. If measurements are collected at baseline and follow-up, changes within the group can also be described. Those observations do not create a concurrent counterfactual: there is no separate group showing what would have happened over the same period without the intervention or with a different intervention.
This distinction is important because change over time can have several explanations. General influences may include the condition's natural course, changes in other care, measurement variation, or participant behavior. Randomization and a suitable comparison group can help address some of these issues, but this registry design does not include a separate randomized control group. A before-and-after pattern, if available, would therefore not by itself identify a causal effect.
What does an event count represent?
The primary endpoint is a count of injection-site skin-reaction events within the stated one-hour timeframe. Counts are different from continuous outcomes such as a laboratory measurement. They are nonnegative and may be sparse, and the distribution can be uneven when events are uncommon or concentrated in a small number of participants.
It is also important to distinguish an event count from the number of participants with at least one event. Repeated events in a participant can make these quantities differ. The registry endpoint description does not say how repeated reactions across injections were aggregated, or whether the analysis unit was an event or a participant. That information is not reported in the registry record.
In general, event counts may be analyzed with count models, or summarized descriptively, depending on the study question and data structure. A Poisson model is one common starting point when its assumptions are appropriate. Over-dispersion occurs when count variability exceeds what such a model expects; ignoring it can make uncertainty estimates too small. Other approaches may be more suitable when there are many zero counts, repeated observations, or clustering within participants. None of these methods should be attributed to this study, because its analysis method is not reported in the registry record.
How should uncertainty be understood?
A point estimate gives a single summary of an outcome, while a confidence interval expresses the range of values compatible with the data under the interval's statistical assumptions. Wider intervals indicate less precision. Small studies often leave substantial uncertainty, particularly for uncommon events, but the size and shape of an interval depend on the observed data and method. The registry information does not give a primary endpoint estimate or confidence interval, so the precision of the reaction count cannot be assessed.
A p-value, when reported, addresses how compatible data are with a specified null model under its assumptions. It does not measure the probability that a treatment works, nor does it describe the size or clinical importance of an effect. The registry record does not report a p-value for the primary endpoint in the information. A lack of a reported p-value is not evidence of no effect; it means that this particular inferential result is not available in the registry record.
How do baseline and follow-up outcomes differ?
The secondary outcomes include change from baseline at follow-up for insulin secretion, as well as changes in HbA1c, fasting glucose, and C-peptide measures. A change score compares a participant's follow-up value with that participant's baseline value. In general, analysis choices can include modeling follow-up values with baseline adjustment or analyzing change scores. These approaches can behave differently depending on measurement variability and the relationship between baseline and follow-up.
The registry lists insulin secretion change from baseline at 5 months and 12 months, but it does not describe the corresponding statistical models, summaries, or handling of repeated measurements. It also does not report whether the same participants contributed data at each follow-up. No particular analysis procedure should therefore be presumed.
What does the planning illustration mean?
Sample-size illustrations are planning calculations, not observed results and not a measure of the study's observed power. The registry description of the planning assumptions specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. For time-to-event calculations, the described quantity is a total event count; for other calculations, it is participants per arm for 80% power or another stated target.
Those assumptions describe hypothetical planning scenarios and do not change the actual design, which is single group. The registry record does not report the study's own sample-size justification. The observed effect needed to interpret an effect-based planning illustration is not reported in the information, and a planning calculation cannot substitute for the study's outcome estimates or uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures and 10 analyses, including a primary skin-reaction endpoint and secondary outcomes covering insulin secretion and metabolic measures. When a study examines multiple outcomes or conducts multiple analyses, the chance of at least one apparently unusual result can increase if each is considered separately. General approaches to multiplicity include identifying a primary outcome in advance, adjusting inferential thresholds, or treating secondary results as exploratory. The registry record does not report whether any such approach was used, how the analyses were prespecified, or how the listed outcomes map to the analyses.
Missing data can also affect interpretation. If follow-up values are unavailable for some participants, the results may depend on who contributed observations and why other observations are absent. General methods range from analyses of available observations to model-based approaches or sensitivity analyses. These methods rely on different assumptions, and no single approach can be inferred simply from the outcome list.
The registry record does not report the analysis population, the amount or pattern of missing outcome data, reasons for missingness, or a missing-data method. It also does not describe whether analyses followed an intention-to-treat principle or another population definition. The enrollment of 14 is not by itself enough to determine how many participants contributed to each endpoint or follow-up analysis.
Without these details, readers cannot assess whether outcome-specific denominators varied, whether missingness could have influenced estimates, or how multiplicity was addressed. These are reporting gaps, not proof that particular procedures were or were not followed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| GAD-vaccination With Vitamin D Suppletion | 2 | 14 | 14.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GAD-vaccination With Vitamin D Suppletion | 0 of 14 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GAD-vaccination With Vitamin D Suppletion | 12 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | GAD-vaccination With Vitamin D Suppletion |
|---|---|---|
| Angina unstable | Cardiac disorders | 1 of 14 |
| Muscle rupture | Injury, poisoning and procedural complications | 1 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GAD-vaccination With Vitamin D Suppletion |
|---|---|---|
| General disorders and administration site conditions | General disorders | 6 of 14 |
| COVID-19, nasopharyngitis, upper respiratory tract infection | Infections and infestations | 6 of 14 |
| Vertigo or vertigo positional | Ear and labyrinth disorders | 2 of 14 |
| diarrhoea | Gastrointestinal disorders | 2 of 14 |
| Nasal congestion and throat irritation | Respiratory, thoracic and mediastinal disorders | 2 of 14 |
| Lymphadenopathy | Blood and lymphatic system disorders | 1 of 14 |
| Tachycardia | Cardiac disorders | 1 of 14 |
| Pancreatic cystadenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 14 |
| Biliary colic | Hepatobiliary disorders | 1 of 14 |
| Procedural dizziness | Injury, poisoning and procedural complications | 1 of 14 |
Serious events with the highest arm-level rate: angina unstable (7.1%), muscle rupture (7.1%).
The registry safety summary reports serious adverse events for 2 participants among 14 at risk, and other adverse events for 12 participants among 14 at risk. It lists 0 deaths. The top serious terms are “Angina unstable” and “Muscle rupture,” each reported as 7.1%. These figures should be read as registry entries for this study group, not as a comparison with another treatment or with an untreated group.
A serious adverse event is a category distinct from an event's possible relationship to treatment. The counts alone do not establish that the intervention caused an event. The registry information does not give individual case descriptions, event timing, duration, severity details beyond the serious classification, or the investigators' causal assessments. It also does not explain whether participants with serious events were included among those with other adverse events, so the categories should not be added together.
The event terms and percentages provide a concise signal of what was recorded, but the record does not provide enough detail to evaluate each event's clinical context. The absence of a reported death count should be interpreted as the registry's reported 0 deaths, not as a broader guarantee about safety.
12. What the Result Does, and Does Not, Mean
This study asks a focused feasibility and safety question about intra-inguinal lymph-node GAD-alum injections accompanied by oral vitamin D in people with LADA. The registry describes the intervention schedule and names immediate injection-site skin reactions as the primary endpoint. It also lists insulin secretion and metabolic outcomes as secondary measures.
The information reported in the registry record does not include the numerical result for the primary endpoint or numerical findings for the listed insulin-related outcomes. It therefore does not establish how often skin reactions occurred, how insulin secretion changed, or how precisely any outcome was estimated. The study's stated aims should not be mistaken for findings.
The safety summary records serious and other adverse events in the study group, including the listed serious terms, and reports 0 deaths. These are descriptive safety data. Without a comparator and without detailed event attribution, the registry counts cannot show whether the events were caused by the intervention or whether their frequency differs from what would occur under another approach.
The design also matters for interpreting any change from baseline. In a single-group, unmasked study, any observed change could reflect influences besides the intervention. A comparison group would provide a basis for assessing how outcomes differ under alternative conditions; this registry design does not provide one.
Thus, the record supports a description of the pilot study's design, planned intervention, outcome topics, and reported safety counts. It does not support a quantified conclusion about the primary endpoint or treatment-related changes in insulin production. A result not reported in the registry record should not be read as either a favorable or unfavorable result.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the difference between a pilot study's objectives and the evidence that can be interpreted from its registry record. The study was designed around safety, feasibility, immune effects, and preservation of endogenous insulin production, but the posted information does not include numerical primary or metabolic outcome results. Clear separation of objectives from reported estimates is essential for avoiding conclusions that go beyond the data available.
The single-group design makes the interpretive role of comparison especially visible. Describing outcomes after an intervention can be useful for characterizing what happened among participants, but it does not reveal what would have happened under a different approach. This is a core issue in clinical inference, not a criticism unique to this condition or intervention.
The primary outcome is an event count. Understanding how such an endpoint is defined, how repeated events are handled, and what uncertainty accompanies the estimate is important when interpreting tolerability. The registry gives a short timeframe and examples of reaction types, but does not report the endpoint result or aggregation details. Those reporting elements would make the result easier to assess.
The record also lists multiple outcomes and analyses without describing multiplicity handling, missing-data procedures, or analysis populations. These are central to interpreting precision and potential selection effects. Finally, the safety counts demonstrate why event descriptions and attribution matter: a recorded serious event is not, on its own, proof of causation. Taken together, the record illustrates how design, endpoint definition, statistical reporting, and cautious interpretation work together in a clinical trial.
14. 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. It is a single-group study with no randomized comparator and no masking. Consequently, the design does not support a direct comparison with an alternative group, and any within-group change cannot by itself separate intervention effects from other influences over time.
The enrollment was 14, and the study is described as a pilot. The registry record does not report a sample-size justification or explain the precision targeted for the primary endpoint. The planning assumptions described for sample-size illustrations are not the trial's own design justification and do not replace observed outcome estimates.
The primary endpoint is defined as injection-site reactions one hour after injection, but the registry information does not report its numerical result or explain the unit of analysis for repeated reactions. The listed secondary outcomes likewise lack numerical findings in the available record. The absence of those results prevents assessment of effect size and precision.
Important analysis details are not reported in the registry record, including the statistical analysis plan, analysis population, missing-data handling, and approach to multiple outcomes and analyses. The safety summary provides counts and selected event terms, but not detailed case context or attribution. These omissions restrict the conclusions that can be drawn from the registry entries, without establishing what procedures or findings may exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes — NCT04262479.
- Registry record last updated 2025-06-08; status last verified 2025-06.
- Results first posted 2025-06-08.
- 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.
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18. Record Summary
The registry record describes a completed phase 2 pilot study of GAD-alum injections with vitamin D supplementation in people with LADA. The study was single group, unmasked, and had an enrollment of 14. Participants were scheduled for 3 injections of 4 µg GAD-alum one month apart, with vitamin D given for 120 days according to the recorded schedule.
The primary endpoint was injection-site skin reactions one hour after injection. Secondary outcomes included insulin secretion and metabolic measures. The registry reports safety counts of 2 participants with serious adverse events, 12 with other adverse events, and 0 deaths; it lists “Angina unstable” and “Muscle rupture” at 7.1% each among the top serious terms.
Numerical results for the primary endpoint and listed metabolic outcomes, along with the statistical analysis plan, missing-data methods, and analysis population, are not reported in the registry record. The available information therefore supports a design and safety-summary description, but not a quantified assessment of treatment-related outcome changes.