Islet Transplantation Moves Toward an Approved Treatment for Severe Type 1 Diabetes
An unprecedented collaborative study across North America has found that islet transplantation — the transplant of the pancreatic cell clusters that contain insulin-producing cells in the pancreas — was effective in preventing severe hypoglycemia, or low blood sugar levels, in the treatment of the most severe forms of type 1 diabetes. Eight centers, including the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine, participated in the trial. Severe hypoglycemia is a particularly feared complication in type 1 diabetes that can lead to seizures, loss of consciousness and even death.
The Phase 3 trial was conducted by the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium. The investigators designed the study in consultation with the U.S. Food and Drug Administration to enable potential future licensure of the manufacture of purified human pancreatic islets. The results were published online April 18 in the journal Diabetes Care.
In type 1 diabetes, the immune system attacks and destroys insulin-producing cells in the islets of the pancreas. People with type 1 diabetes need lifelong treatment with insulin, which helps transport the sugar glucose from the bloodstream into cells, where it serves as a key energy source. Even with insulin therapy, people with type 1 diabetes frequently experience fluctuations in blood sugar levels.
Hypoglycemia, or low blood sugar, typically is accompanied by symptoms such as tremors, sweating and heart palpitations. Those who do not experience these early warning signs — a condition called impaired awareness of hypoglycemia — are at increased risk for severe hypoglycemic events, during which the person is unable to treat themselves.
“The findings suggest that for people who continue to have life-altering severe hypoglycemia despite optimal medical management, islet transplantation offers a potentially life-saving treatment that in the majority of cases eliminates severe hypoglycemic events, while conferring excellent control of blood sugar,” said Anthony S. Fauci, M.D., Director of the National Institute of Allergy and Infectious Diseases (NIAID), one of the NIH centers that funded the study.
One year after the first transplant, 88 percent of study participants were free of severe hypoglycemic events, had established near-normal control of glucose levels, and had restored hypoglycemic awareness. After two years, 71 percent of participants continued to meet these criteria for transplant success.
Even a small number of functioning, insulin-producing cells can restore hypoglycemic awareness, although transplant recipients may need to continue taking insulin to fully regulate blood glucose levels. Participants who still needed insulin 75 days after transplant were eligible for another islet infusion. Twenty-five participants received a second transplant, and one received three. After one year, 52 percent of study participants no longer needed insulin therapy.
“This phase 3 trial could allow the U.S. centers to file a Biologic License Application with the FDA for islet transplantation for treatment of the most severe cases of type 1 diabetes,” said Camillo Ricordi, M.D., Stacy Joy Goodman Professor of Surgery, Distinguished Professor of Medicine, professor of biomedical engineering, microbiology and immunology, Director of the Diabetes Research Institute at the Miller School of Medicine, and Chairman of the Steering Committee of the NIH CIT Consortium. “This could become the first biologically active cell product ever approved in the U.S.”
Currently in the U.S., islet transplantation remains an experimental procedure, but it is already available to patients in other countries, where it is an approved procedure.
“At this time, islet transplantation still requires the use of immunosuppression and therefore is indicated in a very small group of subjects that, despite management of diabetes mellitus under the care of a diabetes specialist, continue to have life-threatening, severe hypoglycemia,” said Rodolfo Alejandro, M.D., professor of medicine and Director of the DRI Clinical Cell Transplant Program at the Miller School.
The Diabetes Research Institute has been contributing technology and equipment for clinical islet transplantation to academic centers worldwide, including the NIH Consortium that completed this unprecedented effort to standardize protocols across North America. Among the equipment used by each center was the Ricordi Chamber, the core element of an automated method for isolating human pancreatic islets, which was invented by Ricordi and collaborators, significantly improving the success of islet transplantation.
The researchers are continuing to follow participants to determine whether the benefits of restoring near-normal blood glucose control and protection from severe hypoglycemic events will outweigh the risks associated with chronic immunosuppression.