Islet Transplantation Alone (ITA)
The ITA trial was initiated in 2004 to evaluate the safety and effectiveness of islet transplantation in treating type 1 diabetic subjects suffering from life-threatening hypoglycemia (low blood sugar) and/or unrecognized episodes of hypoglycemia. Safety was monitored by tracking side effects reported by subjects and observed during frequent post-transplant clinic visits. To evaluate the effectiveness of the islet transplant procedure, the trial also tracked the number of study subjects off insulin and hypoglycemia-free at 3, 6, 12 and 24 months from the time of their final transplant.
As of the end of the study, 17 patients participated in the ITA trial. Fifteen subjects have completed treatment follow-up and all were able to discontinue insulin injections for various periods of time after receiving two to four separate islet transplants (average 2.7 transplants per subject). Results from these subjects are represented in the first two graphs below.
Figure 1. Decline in Daily Insulin Requirement at five Weeks Post-Transplant
Average daily insulin requirements before transplant and at five weeks post each transplant (n=14) are seen in Figure 1 above. This drastic reduction in the need for insulin reflects the quality of the islets transplanted. Insulin independence could not often be sustained for periods greater than one to two years. This may be due to chronic rejection, cell exhaustion or other causes. Many recipients were able, however, to remain on lower doses of insulin for additional years, reflecting varying degrees of continuing islet function.
Episodes of hypoglycemia (low blood sugar) were also eliminated in all subjects by three months post-transplant and remained drastically reduced throughout treatment follow-up as illustrated in Figure 2 below.
Figure 2. Reduction/Elimination of Hypoglycemia Post-Transplant
The number of hypoglycemic episodes reported per week is based on patient-recorded glucose measurements. The number of readings ≤ 60 mg/dL were totaled each week and averaged across the transplant period (pre vs. post). All nine patients were at zero episodes at 24 months. Multiple patient lines overlap after the three month post-transplant period and may not be seen on the graph.
Figure 3: An Example of Long-term Benefits of Islet Transplant
Figure 3 illustrates the goal and potential of islet cell transplant. After a first islet transplant succeeded in reducing the patient’s insulin needs and the number of low blood sugar episodes, the patient received a second islet transplant. Since the second islet transplant in late 2009, no further injectable insulin has been required. Hypoglycemic episodes (low blood sugar less than 80 mg/dL) also decreased to just a handful in the past four years. Most patients have not had the same prolonged period of insulin-independence.
Islet After Kidney Transplantation (IAK)
The IAK trial sought to evaluate the safety and efficacy of islet transplantation in patients with type 1 diabetes and a history of end-stage renal disease successfully treated with renal transplant. As with the ITA trial (above), safety was monitored by tracking side effects reported by subjects and observed during frequent post-transplant clinic visits. The same outcomes measures were used to evaluate efficacy. Renal graft function and quality of life were also tracked for changes.
Three subjects received islet transplantation after a previous kidney transplant under the IAK trial and one is still in an extended period of follow-up study. All patients retained their kidney grafts without any incidents of rejection. Given the small number of participants in this study, the results may not allow for significant analysis or be applicable to current studies; however, two of the three subjects required less injectable insulin and had fewer dangerous episodes of hypoglycemia (low blood sugar) in the period immediately after transplant.