Investigational stem cell infusion therapy shows promise in treating labile type 1 diabetes

The vast majority of people with diabetes have a form of disease that makes the condition manageable with insulin pumps and glucose monitoring devices. However, a subset of patients remains refractory to these interventions. Some experience severe, recurrent hypoglycemic episodes that often require medical attention. Others develop hypoglycemia unawareness, in which autonomic symptoms of low glucose are absent despite otherwise well-controlled blood sugars, increasing the risk of life-threatening events.

Researchers at Baylor University Medical Center (Baylor Dallas), part of Baylor Scott & White Health, are currently recruiting individuals with severe hypoglycemia to participate in a clinical research study of an investigational islet cell infusion therapy. The FORWARD Study, a Phase 3, international, multicenter trial, is studying the safety, tolerability and effectiveness of this investigational therapy.

“The preliminary Phase 1 and 2 results, which were published June 20 in the New England Journal of Medicine, are impressive,” says J. Sebastian Danobeitia, MD, PhD, an abdominal transplant surgeon specializing in liver, kidney, pancreas and islet transplantation on the medical staff at Baylor Dallas and principal investigator for the trial. “Among participants who completed the trial, all were free of severe hypoglycemic episodes, and had HbA1c levels below 7 percent – outcomes that exceed what most insulin-dependent patients can typically achieve. On average, participants spent more than 70 percent of their time within the target glucose range, and 83 percent were completely insulin independent by the end of the first year. We’re very excited to continue studying this therapy.”

The therapy consists of a mixture of islet cells derived from stem cells. The investigational islet cells are delivered to participants through an infusion in the portal vein. Participants will be required to use immunosuppression medications for the duration of the study, which is at least five years. All participants in the study will receive the investigational therapy.

Key eligibility criteria for the FORWARD study are male or female between 18 and 65 (inclusive), blood type A or AB and a BMI of 18 to 30. Participants must have an HbA1c between 6.5 percent and 9.5 percent at screening. Individuals with significant active infection or chronic infection that could be worsened by immunosuppression, or with advanced diabetes-related complications, are not eligible to participate.

“The eligibility criteria are very strict,” Dr. Danobeitia says. “Participants need to be in good overall health aside from having type 1 diabetes. While the infusion procedure is generally safe, it is not non-invasive. It requires a catheter to be placed in the portal vein by an interventional radiologist, which carries a small risk of bleeding or thrombosis that could affect the liver. And because long-term immunosuppression is required, we’re looking for individuals who are most likely to benefit from the treatment while being able to tolerate its demands.”

Once the efficacy of this infusion therapy is validated through the rigorous process required by the FDA, more patients may have access to transplant. For instance, individuals with diabetes often require kidney transplants due to diabetic nephropathy. However, poorly controlled glucose can damage the new kidney as well. By stabilizing blood sugar through islet cell therapy, patients may better protect their transplanted organ. In such cases, a single immunosuppressive regimen could support both the islet cells and the kidney graft.

“This investigational therapy holds great promise for treating labile diabetes, but has much broader implications,” Dr. Danobeitia says. “Science is advancing so rapidly that I wouldn’t be surprised if, in the near future, we’re able to engineer stem cell-derived islet cells that are immune-evasive, eliminating the need for long-term immunosuppression altogether.”