Scientists at the Massachusetts General Hospital (MGH) have initiated a phase 1 clinical trial to reverse type 1 diabetes. The trial is exploring whether the promising results from the laboratory of Denise Faustman, Associate Professor of Medicine at Harvard Medical School, can be applied in human diabetes.
A phase 1 trial is usually designed to determine the safety, side effects, and dosage range of a treatment, rather than its usefulness. If the proposed treatment is found to be safe, then researchers may initiate a phase II trial, to test for efficacy, in a relatively small group of subjects.
In previous studies Faustman has demonstrated that mice can be cured of
a form of diabetes closely resembling type 1 in humans. Those
studies used Bacillus Calmette-Guerin (BCG), a common tuberculosis
vaccine, to deplete the abnormal immune cells that attack and destroy
the insulin producing cells of the pancreas. The first step in the
human study, which is currently enrolling volunteers, is to determine
whether the same strategy using BCG vaccination can be used to modify
the abnormal autoimmune cells present in type 1, or so-called “juvenile
David M. Nathan, MD, director of the MGH Diabetes Center, who is
leading the human study at MGH, cautions that this “this is the very
first step in what is likely to be a long process in achieving a cure.
We first need to determine whether the abnormal autoimmune cells that
underlie type 1 diabetes can be knocked out with BCG vaccination, as
occurred in the mouse studies.”
“We are pleased to be starting human clinical trials,” Faustman said. “Human trials take time, but we are making the step from curing diabetes in mice to determining whether it will work in men and women with diabetes.”
Type 1 diabetes, which usually begins during childhood or adolescence, is triggered when the immune system attacks and destroys the insulin-producing cells in the
pancreas. In the absence of insulin, which is necessary for sugar and
other nutrients to enter cells, blood sugar levels rise and can cause a variety of severe complications, including kidney failure, loss of vision, amputations, heart disease, and strokes.
The risk for developing complications is closely linked to the elevated blood sugar levels over time. If blood sugar levels are well controlled, the onset of long-term complications can be delayed, and sometimes largely avoided. However, the intensive, on-going therapy required to maintain near-normal sugar levels places life-long demands on the patient, including frequent blood sugar monitoring and at least 3 daily injections of insulin or use of an insulin pump, along with restrictive diets. Insulin doses must be adjusted based on blood sugar levels, dietary factors, and anticipated exercise. Thus, a cure for diabetes has been highly sought after and has attracted much research interest.
The clinical trial is using the BCG vaccine because it causes a low-grade inflammatory reaction, which in the mouse
model of autoimmune diabetes lead to the destruction of the abnormal
autoimmune cells. It is a particularly attractive candidate vaccine because it has been used safely for nearly 80 years as a tuberculosis vaccine.
The Phase I trial is being supported largely through direct and fund raising support from the Iacocca Foundation, and through support from other donors and the Massachusetts General Hospital. The Iacocca Foundation was founded by Lee Iacocca and his family in 1984 to fund innovative approaches to a potential cure for diabetes.
Prospective trial participants should contact the MGH Diabetes Center at 617-726-1847.