Can a vaccine designed to prevent tuberculosis also prevent the worst complications of Type 1 diabetes?
Researchers in Boston are moving forward with clinical trials to try to learn the answer to that question. The U.S. Food and Drug Administration recently approved moving forward with the second phase of clinical trials at Massachusetts General Hospital in Boston to determine if repeated doses of a generic tuberculosis vaccine can spur clinical improvements in adults with advanced Type 1 diabetes. Type 1 diabetes is an autoimmune disease, which occurs when the body’s own immune system attacks insulin-producing cells in the body, requiring an individual to inject insulin in order to regulate blood sugar levels.
How does the vaccine prevent diabetes?
Previous tests of the bacillus Calmette-Guérin (BCG) vaccine in mice and humans found that two doses administered four weeks apart temporarily eliminated the immune cells that destroy the pancreas’ ability to produce insulin. As a result, patients demonstrated what researchers described as a “small, transient” return to producing insulin secretions.
For the new phase of the trial, adults who’ve had diabetes for many years will receive multiple doses of the vaccine over a five-year period. Researchers want to determine if increased levels of the vaccine will ease the immune system’s destructive actions and improve blood sugar control. They’ll test patients’ A1c levels and other clinical markers to see if the vaccine leads to better blood sugar control over time. A1c is a blood marker used to gauge blood sugar control; patients whose A1c levels are within clinical guidelines have fewer diabetes-related complications, including heart disease and stroke, vision loss and neuropathy.
Researchers led by Dr. Denise Faustman, director of the Massachusetts General Hospital Immunobiology Laboratory will recruit 150 adults who are 18 to 60 years of age for the study. Half will receive the TB vaccine; half will receive a placebo.
“In the phase I clinical trial, we demonstrated a statistically significant response to BCG, but our goal in phase II is to create a lasting therapeutic response,” Dr. Faustman, an associate professor of Medicine at Harvard Medical School, said in a press release from Massachusetts General. “We will be working again with people who have had Type 1 diabetes for many years. This is not a prevention trial; instead, we are trying to create a regimen that will treat even advanced disease. In addition to our phase I trial, we took guidance from the BCG clinical trials that are underway globally for other autoimmune diseases such as multiple sclerosis.”
What can the vaccine do?
Faustman and her team hope the vaccine will provide a tool to help prevent dangerous complications associated with long-term Type 1 diabetes, though researchers and people affected by the disease continue to search for a cure.
“This sort of innovative thinking is our best hope for finding a cure for Type 1 diabetes. It is still way too early to know whether the BCG vaccine will be able to do that or not,” said Dr. Linda Hermiller, an endocrinologist with the St. Elizabeth Regional Diabetes Center in Covington. “The first phase I trial was very small and showed promise, but BCG is not likely to be a true cure. The underlying concept of reducing the ‘negative’ immune system behavior to stop or retard the destruction of the islet cells is at the heart of most of the trials trying to ‘cure’ Type 1 diabetes.”
None of the data show the vaccine restores or revives the cells that produce insulin, she added.
The BCG vaccine has been used to prevent tuberculosis for more than 90 years. It’s also FDA-approved to treat bladder cancer.
The vaccine works by increasing levels of TNF, or tumor necrosis factor, which produces more helpful immune cells that protect the pancreas’ ability to produce insulin and reduces the number of harmful immune cells that attack the pancreas, Dr. Faustman said.
