Researchers announced the approval of a new phase II clinical trial to test whether a vaccine can reverse type 1 diabetes.
The five-year trial, announced at the annual meeting of the American Diabetes Association, will investigate whether the bacillus Calmette-Guérin (BCG) vaccine can improve type 1 diabetes in adults who have detectable levels of insulin secretion from the pancreas.
Autoimmune research, over the years, had also identified an immune protein, tumor necrosis factor, or TNF, that can selectively kill bad T-cells while sparing the healthy ones. The challenge was finding a way to increase TNF safely.
Enter BCG, an inexpensive drug that is used in the vaccination against tuberculosis and for the treatment of bladder cancer. BCG also raises levels of TNF. In studies in mice, the research team, led by Denise Faustman, MD, PhD, director of the Massachusetts General Hospital Immunobiology Lab, found that raising TNF can rid the blood of the bad T cells.
In a Phase 1 clinical trial in humans, published in 2012, Faustman showed that BCG can eliminate the bad T cells and found evidence of a small, temporary return of insulin secretion in people who have had type 1 diabetes for many years. “Although the drug was given in relatively small doses, we saw targeted death of the ‘bad’ T cells that attack the insulin-secreting islets, an early sign that BCG has the potential to stop the autoimmune attack and successfully reverse disease,” wrote the authors. The short four-week Phase 1 trial importantly found that the treatment was safe with few side effects.
"We have learned a lot since the early studies in mice - not just about how BCG works but also about its potential therapeutic benefits, similar to what are being seen in trials against other autoimmune diseases," says Faustman.
The new phase II clinical trial of 150 adults with long-term type 1 diabetes will investigate whether more frequent BCG vaccinations over four years can improve their condition. This is not considered a prevention trial, but a treatment for those with type 1 diabetes. Patients will be randomized to receive two injections four weeks apart of either BCG or placebo and then a single injection annually for the next four years.
The goal of the study is to see what dose and frequency is needed to put diabetes 1 into remission and prevent long-term complications.
1. PLoS ONE, August, 2012; http://www.faustmanlab.org/docs/academic/JournalPone0041756.pdf