Phase 3 Trial Results Raise Hopes That Islet Transplants Could Soon Treat Type 1 Diabetes

The results, published in Diabetes Care, move the hope of pancreatic cell islet transplants close to commercialization, which would bring the technique to more patients who cannot produce their own insulin.

Promising results from a phase 3 trial involving pancreatic islet transplants are raising hopes that this treatment could soon be available for persons with type 1 diabetes (T1D) and severe lack of hypo-awareness—meaning they do not know when their blood sugar is dropping.

Results from the trail were published today in Diabetes Care and announced by the National Institutes of Health (NIH), which funded the study.1,2 The study involved 48 people with T1D and severe lack of hypoglycemia awareness, despite what was described as “expert care.”

A year after the first transplant, 88% of the participants were free of severe hypoglycemic events and had reached “near-normal control of glucose levels” along with restored hypo-awareness, according to an NIH. After 2 years, those results continued for 71% of the transplant recipients.1

Patients’ median glycated hemoglobin (A1C) 5.6% (38 mmol/mol) at both the 1-year and 2-year mark, according to the abstract.2

The trial took place at 8 of the 13 centers that make up the Clinical Islet Transplantation Consortium. Ten centers are located across the United States, 1 is in Canada and 2 are in Sweden.

Severe episodes of hypoglycemia are among the most dangerous health risks faced by persons with T1D. These incidents can produce loss of consciousness or death, as the person is unaware that blood sugar levels are dropping. While some patients experience sweating or heart palpitations during an onset of hypoglycemia, those with impaired awareness do not—thus they are at greatest risk losing consciousness and being unable to care for themselves.

The transplantation technique involves clusters of insulin-producing cells being injected into portal vein, which brings blood from intestine to the livers. The pancreatic cells are purified islets from the deceased human donors. Unsurprisingly, a potential side effect of this process is a reaction to the immunosuppressive drugs that recipients must take to avoid rejecting the cells. According to the abstract, 2 enrollees (4.1%) had infections that were attributed to the immunosuppressive drugs.

“While still experimental, and with risks that must be weighed carefully, the promise of islet transplantation is undeniable and encouraging,” said Griffin P. Rodgers, MD, director of the National Institute of Diabetes and Digestive and Kidney Diseases. “Even with the best care, about 30% of people with type 1 diabetes aren’t aware of dangerous drops in blood glucose levels.”

“The findings suggest that for people who continue to have life-altering severe hypoglycemia despite optimal medical management, islet transplantation offers a potentially lifesaving treatment, that in the majority of cases eliminates severe hypoglycemic events while conferring excellent control of blood sugar,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Disease, the other NIH section that funded the study.

T1C affects about 1.25 million people in the United States, and its incidence is growing worldwide for reasons that are not well understood. Patients who have this disease cannot produce their own insulin after their immune system destroys this mechanism in the pancreas, robbing them of the hormone that carries blood sugar to cells, where it becomes an energy source. Even with insulin therapy, T1D patients must follow a strictly regulated diet to control fluctuations in blood sugar levels.

Study co-author Nancy D. Bridges, MD, who is the NIAID Transplantation Branch chief, said the trial is the first that will enable the cellular product to be licensed, a must before any product can seek FDA approval. “Licensure is critical because it will ensure quality, consistency, and safety of the islet product; provide greater patient access to the islet transplantation; and accelerate continued research that we hope would make this procedure suitable for a broader population of people (with T1D).”

References

1. Islet transplantation restores blood sugar awareness and control in type 1 diabetes [press release]. Bethesda, MD: National Institutes of Health; April 18, 2016. https://www.nih.gov/news-events/news-releases/islet-transplantation-restores-blood-sugar-awareness-control-type-1-diabetes

2. Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016; DOI: 10.2337/dc15-1988.