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 Multicenter Trial of the Effect of AAT on Islet Transplant Engraftment and Durability After Renal Transplant (NCT02464878), a na phase 2 study. The primary outcome is The Proportion of GLASSIA Versus Control CIT06 Subjects Achieving Insulin Independence After First Infusion of Single Donor Islets..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02464878 |
| Phase | Phase 2 |
| Condition | Kidney Transplant, Type 1 Diabetes |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
People with kidney transplant and type 1 diabetes who met the study entry criteria. The registry record describes two enrolled subjects and says the available information pertains to those two subjects.
Intervention
Alpha 1-antitrypsin (AAT) infusions around the time of islet transplantation. The study description says participants would receive 1-3 infusions of in vitro cultured islets and AAT infusions three times a week for three weeks in the peri-transplant period. Other listed interventions include islet transplantation, Thymoglobulin, Basiliximab and Etanercept; their specific schedules are not reported in the registry record.
Comparator
The intended comparison was with control CIT06 subjects from NCT00468117. This was not a randomized, like-for-like control comparison, and the registry record says reduced enrollment prevented a statistically appropriate comparison.
Primary question
What proportion of GLASSIA-treated subjects achieved insulin independence after the first infusion of single-donor islets, assessed at Day 75? The endpoint was defined using insulin use, glucose measures, HbA1c and C-peptide criteria. A comparative estimate between the treated subjects and the control cohort is not reported in the registry record.
The study's clinical question combines an early post-transplant outcome with a comparison to a control cohort. Insulin independence is not defined simply as stopping insulin: the registry description requires documented measurements around the Day 75 visit and specified glucose, HbA1c and C-peptide conditions. This makes the endpoint a composite status based on treatment use and metabolic measurements.
The registry lists further questions about insulin independence after one or more islet infusions, glycemic status and severe hypoglycemic events, changes in Clarke score, additional islet transplants, and cardiovascular events and atherogenic profile. These are planned outcome topics in the record, not evidence that comparative effects were established. The registry record does not report comparative analysis results for these outcomes.
3. Trial Design
This was a completed phase 2, single-group study sponsored by Massachusetts General Hospital. The registry lists enrollment of two and describes participants receiving AAT in the peri-transplant period in connection with islet transplantation. The study began in 2017-01 and primary completion was in 2022-11. The registry lists the study status as completed.
The brief description says eligible participants would receive 1-3 infusions of in vitro cultured islets and AAT infusions three times a week for three weeks in the peri-transplant period. Islet transplantation, Thymoglobulin, Basiliximab and Etanercept are also listed as interventions. The registry record does not report further treatment schedules or enough detail to determine how each listed intervention was administered to each participant.
The primary outcome is framed as a comparison of GLASSIA-treated subjects with control CIT06 subjects from NCT00468117. However, the study is recorded as single-group, allocation is listed as NA, and masking is listed as none. The registry explicitly says reduced enrollment prevented a statistically appropriate comparison. Thus, the comparison in the outcome wording should not be read as evidence of a concurrent randomized control arm or as a reported estimate of a treatment contrast.
The registry record does not report a sample-size justification, a planned statistical analysis approach, interim analyses, or a detailed account of participant flow. It lists nine outcome measures but reports no analyses. Without outcome estimates or participant-level results, the record supports a description of the study design and outcome definitions, not a quantified assessment of comparative efficacy. The small enrollment also means that even descriptive observations from these participants should be understood as specific to this very limited study cohort.
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 | Main Study Treatment |
|---|---|
| STARTED | 2 |
| COMPLETED | 2 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Due to reduced enrollment in study, unable to make statistically appropriate comparison between subjects receiving GLASSIA and Control CIT06 subjects from NCT00468117. Information provided is pertinent to the two subjects enrolled based on descriptions of Primary and Secondary Outcomes
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 | Main Study Treatment |
|---|---|---|
| Participants analysed | 2 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 51 (44 to 58) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as The Proportion of GLASSIA Versus Control CIT06 Subjects Achieving Insulin Independence After First Infusion of Single Donor Islets., measured over Day 75.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the count or proportion of participants achieving insulin independence after the first infusion of single-donor islets, assessed at Day 75. The registry defines insulin independence as the ability to titrate off insulin therapy for <1 week while meeting additional requirements. Measurements are expected within the Day 70-80 visit window, with seven days of blood sugar and insulin readings documented within the Day 63-87 window.
The definition also requires a specified HbA1c condition, limits on fasting capillary glucose readings, post-prandial serum glucose at 90 minutes during a mixed meal tolerance test, a fasting serum glucose threshold, and at least one fasting or stimulated C-peptide result. The HbA1c condition is stated as <= 6.5% or a >= 2.5% decrease from baseline, with baseline defined as within 91 days before transplant. These conditions make the endpoint more specific than insulin cessation alone: it combines treatment status with documented metabolic measurements.
Such a defined endpoint can make the meaning of “insulin independent” consistent within a study, since it specifies both the assessment period and the criteria for classifying participants. The registry record does not report how many participants met the endpoint, so no observed primary outcome proportion or comparative estimate is available from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed study with enrollment of two, but it does not report an observed primary endpoint result or a statistical comparison with the control CIT06 cohort. It also states directly that reduced enrollment made a statistically appropriate comparison impossible. The key interpretation is therefore about the limits of what can be concluded from the record: it documents the study question and endpoint criteria, but does not provide a comparative effect estimate.
The primary endpoint is a participant-level classification at Day 75. It requires documented insulin titration and a combination of laboratory and glucose criteria. Because no outcome counts or individual results are reported, it is not possible to determine from the registry record how many of the two enrolled participants met that definition. A comparison with control subjects cannot be reconstructed from the endpoint title alone.
The design also matters. A single-group study is not a randomized comparison, and the registry says the intended comparison with CIT06 control subjects was not statistically appropriate given enrollment. Differences between a treated group and an external control group can reflect differences in participant characteristics, timing, measurement, or care, as well as treatment. General statistical interpretation therefore requires caution whenever groups are not formed through a suitable randomized design. The registry record does not provide sufficient results or methods to separate these possibilities.
The listed secondary outcomes concern a range of clinical domains, including insulin independence after additional islet infusions, HbA1c combined with severe hypoglycemic events, Clarke score, additional transplants, and cardiovascular events and atherogenic profile. The record lists these endpoints but does not provide comparative effect estimates or analysis results for them. Their inclusion in a registry outcome list should not be mistaken for evidence that an effect was demonstrated.
The adverse-event record does contain counts. In the main study treatment group, one of two participants was affected by a serious adverse event, and two of two were affected by other adverse events. The listed serious terms are Seizure and Tounge Swelling (Allergic Reaction), each reported as 50.0%. No deaths are recorded. With this small group, these counts describe only the enrolled participants; they cannot establish how frequently events would occur in a broader population or establish a comparison with another treatment.
Overall, the posted information is descriptive and highly limited by enrollment and the absence of reported outcome analyses. It does not supply the primary outcome result, a control-group result, a confidence interval, or a comparative statistical test. Those omissions preclude claims about the size, precision, or statistical significance of a treatment contrast. The absence of a reported estimate is not evidence that the treatment has no effect; it means the registry record does not establish a comparative result.
9. Statistical Methods Explained
The registry describes a single-group phase 2 study and does not report a detailed statistical analysis plan. The primary outcome is expressed as a proportion of participants, but the record does not include the count meeting the endpoint, the denominator used for an outcome analysis, or a comparative estimate. Statistical methods should therefore be discussed as general concepts rather than as methods confirmed to have been applied in this study.
What does a participant proportion represent?
For a binary endpoint, each participant is classified into one of two categories, such as meeting or not meeting the stated insulin-independence definition. A proportion summarizes the number meeting the criterion relative to the number assessed. That summary depends on a clear definition of the endpoint and on knowing who was assessed. Here, the registry supplies a detailed endpoint definition and enrollment count, but does not report the primary outcome count or analysis denominator. An observed proportion cannot be derived from the record.
In general, an estimate from a small group is imprecise: each participant's classification has substantial influence on the overall summary. A confidence interval communicates uncertainty around an estimate, rather than only presenting a single value. The registry record does not report a confidence interval for the primary endpoint, and an interval cannot be reconstructed without the relevant outcome data and analysis details.
Why does the comparison design matter?
A randomized comparison is intended to make treatment groups comparable, on average, with respect to factors that might influence the outcome. This study is listed as single-group, with allocation NA and masking none. Its primary outcome wording refers to control CIT06 subjects from a separate study, but the registry states that reduced enrollment prevented a statistically appropriate comparison. An external control is not automatically equivalent to a concurrent randomized control: populations, outcome assessment, follow-up, and background care may differ. General comparisons across separate cohorts can therefore be difficult to interpret causally.
The registry does not report a comparative estimate, statistical test, or adjustment method. It would be inappropriate to infer any of these from the outcome wording. In particular, the fact that an outcome title names a control cohort does not establish that a formal comparison was conducted.
How should statistical significance and precision be distinguished?
In general, a statistical test addresses compatibility between observed data and a specified null hypothesis under assumptions. A p-value does not describe the magnitude or clinical importance of an effect, and it cannot substitute for an effect estimate and its uncertainty. Precision is best assessed from the estimate and its confidence interval, interpreted in light of study design and data quality. No primary comparative estimate, confidence interval, or p-value is reported in the registry record, so statistical significance and precision of a treatment contrast cannot be assessed.
The record includes sample-size planning illustrations based on an observed effect, with stated assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the study was designed or analyzed using those assumptions. The registry record does not report a sample-size justification for the actual study, and no underlying observed effect estimate is reported for evaluating such planning scenarios.
Why can event rates be unstable in a small study?
For binary safety outcomes, a participant may be classified as having experienced at least one event or not. In general, when few participants are observed, a single participant can substantially affect a reported percentage. This makes the percentages descriptive of the enrolled group rather than stable estimates of risk in a wider population. Comparisons of event rates also require information on follow-up, event definitions, and comparable groups. The registry reports event counts for the main study treatment group but does not provide a comparative safety analysis.
When data are over-dispersed in settings where a model assumes a particular level of variation, the observed variability exceeds that assumption. General statistical methods may need to account for that extra variability to avoid overly narrow uncertainty estimates. The primary outcome is binary and no model or dispersion estimate is reported; no over-dispersion adjustment can be attributed to this study.
Finally, statistical methods cannot recover information that was not reported. The record does not describe interim analyses, missing-data procedures, analysis populations, or detailed model specifications. These omissions constrain reproducibility and interpretation. They should be stated as unreported rather than filled with assumptions about what may have been planned or performed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including the primary endpoint and secondary outcomes covering glycemic status, severe hypoglycemic events, Clarke score, repeat islet transplants, and cardiovascular events and atherogenic profile. When several outcomes are examined, general statistical practice considers multiplicity: the more hypotheses tested, the greater the chance of at least one apparently unusual result arising by chance. A prespecified hierarchy or adjustment approach can address this issue, but the registry record does not report a multiplicity strategy or detailed analysis plan.
The record also does not report missing-data procedures, the number of participants assessed for each endpoint, or how incomplete measurements were handled. These details matter for an endpoint requiring measurements in specified visit windows. Without reported assessment and missingness information, readers cannot determine whether all enrolled subjects had adequate data for classification or how any unavailable measurement affected the outcome summaries.
Analysis populations are not described in detail. The record says the information is pertinent to the two enrolled subjects, but does not specify whether an intention-to-treat, per-protocol, or other analysis population was defined. Such labels should not be inferred. The registry also reports no analyses. Consequently, the listed outcomes indicate what the study set out to assess, not a set of completed hypothesis tests with known multiplicity control or missing-data handling.
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 |
|---|---|---|---|
| Main Study Treatment | 1 | 2 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Main Study Treatment | 0 of 2 |
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 |
|---|---|
| Main Study Treatment | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Main Study Treatment |
|---|---|---|
| Seizure | Nervous system disorders | 1 of 2 |
| Tounge Swelling (Allergic Reaction) | Investigations | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Main Study Treatment |
|---|---|---|
| Nausea | Gastrointestinal disorders | 2 of 2 |
| Abdominal Pain/Bloating | Gastrointestinal disorders | 1 of 2 |
| Chest Pain | Cardiac disorders | 1 of 2 |
| Constipation | Gastrointestinal disorders | 1 of 2 |
| Diaphoresis | General disorders | 1 of 2 |
| Diarrhea | Gastrointestinal disorders | 1 of 2 |
| Elevated Creatinine | Infections and infestations | 1 of 2 |
| Elevated Liver Function Tests | Investigations | 1 of 2 |
| Fever | Investigations | 1 of 2 |
| Shingles | Infections and infestations | 1 of 2 |
Serious events with the highest arm-level rate: seizure (50.0%), tounge swelling (allergic reaction) (50.0%).
The registry reports safety information for the Main Study Treatment group, with two participants at risk in both the serious and other adverse-event summaries. One participant was affected by a serious adverse event, and two participants were affected by other adverse events. No deaths are recorded.
The serious terms listed are Seizure and Tounge Swelling (Allergic Reaction), each reported as 50.0%. These are descriptive summaries for the two enrolled participants. The record does not provide enough information to interpret timing, duration, severity beyond the serious-event classification, relatedness to a specific intervention, or whether a participant experienced more than one serious event. The listed terms should not be treated as a comparative safety estimate.
With only two participants, the counts and percentages are particularly sensitive to individual observations. They describe the recorded experience in this study group, not the expected frequency of events in a larger population. No control-group safety comparison is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a small completed phase 2 study examined AAT in the peri-transplant period alongside islet transplantation in people with kidney transplant and type 1 diabetes. It provides a detailed definition of the primary insulin-independence endpoint at Day 75 and lists additional outcomes. It also records safety counts for the two enrolled participants.
It does not establish how many participants met the primary endpoint. The registry does not report the primary outcome count, a comparative result, an effect estimate, or a confidence interval. It explicitly states that reduced enrollment prevented a statistically appropriate comparison with control CIT06 subjects. The record therefore cannot quantify a treatment contrast or its precision.
The absence of a reported comparative result does not demonstrate that there was no effect, and it does not establish that there was an effect. It means the registry record does not provide evidence sufficient to estimate or test a comparative effect. Likewise, the safety counts describe this very small group and cannot establish rates for a broader population or differences from a comparator.
The outcome list should be read as a list of planned or specified measurements, not as a set of results. Without reported analyses and information about missing data or analysis populations, readers cannot determine how each endpoint was assessed across participants. The appropriate conclusion is limited: the record documents the study's question, design features, endpoint definitions and recorded adverse-event counts, while leaving comparative efficacy and broader safety questions unresolved.
13. Why This Trial Matters Statistically
This study illustrates how a registered clinical question and an interpretable comparative result are not the same thing. The primary endpoint is stated in comparative language, but the record identifies the study as single-group and says that enrollment was too low for a statistically appropriate comparison with the external control cohort. Recognizing that distinction prevents an outcome title from being mistaken for evidence of a treatment contrast.
The endpoint definition also demonstrates why operational detail matters in clinical research. Insulin independence is specified using insulin titration, assessment windows, HbA1c, glucose measurements and C-peptide. Such criteria clarify what counts as meeting the outcome, but they do not replace reporting the number assessed, number meeting the definition, or uncertainty around an estimate.
Finally, the record illustrates the limits of interpreting sparse event data. The safety counts and percentages are useful descriptions of what was recorded among the participants, yet the very small group cannot support stable general estimates or meaningful comparative conclusions. For biostatisticians and clinical researchers, this study underscores the importance of transparent reporting of outcome counts, analysis populations, missing-data handling, uncertainty estimates and prespecified methods. Those elements are necessary to distinguish a documented study question from a result that can support a statistical conclusion.
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.
The main limitation apparent from the registry record is enrollment of two participants. The record itself states that reduced enrollment prevented a statistically appropriate comparison with control CIT06 subjects from NCT00468117. The primary endpoint's comparative wording should therefore not be interpreted as a completed comparative analysis.
The registry does not report the primary endpoint result, secondary outcome results, comparative effect estimates, confidence intervals, or statistical tests. It lists nine outcome measures, but no analyses are reported. This leaves the direction and magnitude of any outcome patterns unknown from the record.
Several aspects needed to assess the analysis are not reported in the registry record: the detailed statistical plan, sample-size justification, interim analyses, missing-data approach, analysis populations, participant flow, and detailed methods for comparing outcomes with the control cohort. The record also does not describe the specific schedules for all listed interventions or give enough information to evaluate how outcome measurements were completed for each participant.
For safety, the counts are based on a group of two. The record does not give a comparative safety analysis or sufficient context about event timing and attribution. The reported percentages should consequently be treated as descriptions of the recorded participants, not as precise estimates of risk. These limitations restrict conclusions about comparative effects, generalizability, and the interpretation of the listed outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Multicenter Trial of the Effect of AAT on Islet Transplant Engraftment and Durability After Renal Transplant — NCT02464878.
- Registry record last updated 2023-12-22; status last verified 2023-11.
- Results first posted 2023-12-22.
- 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
NCT02464878 is a completed phase 2, single-group study sponsored by Massachusetts General Hospital. It enrolled two participants with kidney transplant and type 1 diabetes and examined AAT in the peri-transplant period alongside islet transplantation. The registry lists 2017-01 as the start and 2022-11 as primary completion.
The primary outcome concerns insulin independence after the first infusion of single-donor islets at Day 75, using a detailed set of insulin-use and metabolic criteria. The registry says enrollment was too low for a statistically appropriate comparison with control CIT06 subjects. It does not report primary or secondary outcome analyses. Safety information records one participant with a serious adverse event, two with other adverse events, and no deaths. These data are descriptive of the two enrolled participants and do not establish comparative effects.