Many of you may be aware of the recent publication and related news coverage of the 8-year long phase I human trial, which shows that the generic vaccine BCG appears to restore blood sugars to near normal in type I diabetics with long standing disease. This research was performed at the Massachusetts General Hospital and Harvard Medical School and published in a peer-reviewed journal, Nature Vaccine, with Dr. Denise Faustman as the principle investor.
In response to the public announcement of this research, JDRF released a joint statement with the ADA. Of note, JDRF has never supported this research despite many requests for funding. We find that their choice to proactively issue a public statement in response to the media coverage of this human trial is somewhat odd. Although it is certainly within their right, it is not appropriate and not in the best interest of the diabetes community to issue such a statement that deeply understates the potential of this research, implies claims that MGH and Dr. Faustman never make and most of all contains factual errors. We feel compelled to address their minimization of the results and the inaccuracies, which are easily verified in the publication. Specifically:
The BCG treatment resulted in only moderately low HbA1cs and were marginally statistically significant. Untrue. The new data reports highly statistically significant lowering of HbA1c (p<0.0002) in the BCG-treated long-term diabetics. Furthermore, BCG-induced lowering of HbA1c was sustained beyond 5 years in all BCG vaccinated subjects. Hemoglobin A1c of 6.5 is considered the threshold of diabetes diagnosis. The published results showed a durable and statistically significant lowering of HbA1c in the BCG treated group compared to the control group. The BCG treated group started with an average HbA1c of 7.36 and decreased to an average of 6.38 over years 5-8 followed. This is in contrast with the control group’s average HbA1c remaining the same and even slightly increasing from the initial 7.08-7.10 range over the same time period. The HbA1c persistently remained lowered in response to the 2 BCG vaccines and to this day continues to be lowered compared to the placebo treated TID people. This information is in the published paper. As we all know, HbA1c is clinically important because prolonged higher HbA1c levels are directly correlated with greater risks of developing diabetes-related complications.
The newly published data does not account for the natural variability in HbA1c levels over time, which is well known to occur in this population: they tend to improve in people with TID as they age, particularly as they move out of their teens and early 20’s. Untrue. The clinical trial had a simultaneously studied cohort group of untreated type I diabetics that accounted for the natural variability of HbA1c over the entire study. This statement also implies that the BCG treated group may have included people in their teens and early 20’s accounting for HbA1c improvement when in fact the published paper reports that the BCG treated group included nine people at an average age of 45 who were diagnosed between the ages of 22-30 and living with TID for an average of 19 years.
There are no details on the standard of care. Untrue. One person was on a pump in the BCG treated group and no one used a continuous glucose monitor (CGM). There was no change in their therapy regimen as it related to devices such as pumps and CGM devices throughout the trial as stated in the published paper.
All study participants continued to use standard insulin therapy throughout the trial. The published data in this paper does not yet report on the degree or the duration of changes in insulin therapy. However, it is important to point out that semi-annual surveys confirmed that after BCG vaccinations, there were no reports of significant hypoglycemia episodes by any of the BCG treated patients within the years 5-8 followed. This change occurred even with their HbA1c levels lowered and sustained to the near normal range. The placebo group continued to show hypoglycemia events during the same time periods of monitoring. We are all well aware that the recommended target HbA1c has been 7.0 to obtain the best possible blood sugar average while minimizing or eliminating the dangerous lows that often accompany HbA1c values in the low to mid 6.0 range. This is true especially as the years living with the disease increase and hypoglycemia unawareness can develop.
The study only followed a very small number of patients…and must be interpreted with caution. The scientific community uses statistical analysis (relayed in p values) to quantitatively measure the significance of outcomes, and the p values in this study were highly significant. Further, two weeks ago the JDRF issued a very positive public review of a Phase II clinical study using a blood pressure lowering drug in new-onset diabetics of a similar group size.
The JDRF indirectly implies that Dr. Faustman is advocating BCG as a current therapy. Based on the reading of her online materials and our conversations with her, this is not true. The state of this research and that BCG is not yet approved as a treatment for type I diabetes is clearly stated in all of the MGH media materials.
The phase I human clinical trial was a double blinded study using the 100-year old generic and safe BCG vaccine. BCG has been known for over 30 years to boost a cytokine in the body called Tumor Necrosis Factor (TNF). It has been published that TNF directly eliminates the auto-reactive T cells that are responsible for autoimmune disease. A surprise finding in this human study was an increase in the beneficial regulatory T cells called T regs to almost normal levels. The T regs are critical for immune balance and decreasing inflammation and the autoimmune response. Even more impressive was the discovery that blood sugar control may have been driven by a shift in the body’s ability to metabolize glucose from oxidative phosphorylation to aerobic glycolysis (a state of high glucose utilization) on a tightly regulated cellular level systemically. In other words, glucose uptake and regulation of this uptake by the cells appears to prevent severe hypoglycemia since the cells stop transporting glucose when the blood sugar is in the normal range.
The intent of this phase I human clinical trial was never to get the people with long-standing disease off of insulin with 2 BCG vaccinations. We are not aware that MGH ever made that claim because the trial was not designed to answer that question. There is a six-dose 150 patient Phase II trial currently underway at MGH that is designed to do just that. This early phase I trial’s purpose was to satisfy FDA safety requirements and perform specific analysis to detect any immune system effects and document any clinical changes in the participants, no matter how temporary. Surprisingly, the data shows that the clinical changes have been sustained for many years and the immune system effects are profound.
We try to follow many areas of research involving possible treatments that may improve the lives of those living with TID and perhaps lead to a true cure because our children were diagnosed with diabetes in the mid-1990s at 3 years and 18 month of age respectively. We believe that all research should continue as quickly and safely as possible until it rules out if an idea can work or not. With that said, we will stand up and question any person(s) or organization that sheds falsehoods that may be detrimental to the progression of a possible treatment and specifically the ability to obtain funding to continue.
In an environment where health care costs are already unaffordable, and our fears as parents that our children may suffer from a deadly hypoglycemic episode or develop long-term complications, these early findings that BCG may be available as an affordable and safe adjunct therapy for normal blood sugar control in humans with longstanding disease, is something to be excited about. Expanding research to include the pediatric population and newly diagnosed needs to be done as quickly as possibly, especially given the impeccable 100-year safety record of BCG. We urge you to contact JDRF headquarters and tell them to engage with MGH on these current and future BCG human trials.
To learn more about BCG and the research that has been done to validate its potential, including a copy of the recent publication, please visit www.faustmanlab.org.