Chelation Encore: TACT2 Trial Gets Go-ahead for Controversial Post-MI Treatment in Diabetes
Three years after an eye-opening diabetes substudy from the TACT trial was aired at the American Heart Association (AHA) 2013 Scientific Sessions, the National Institutes of Health has granted its blessing—along with $37 million—to a second study of chelation therapy zeroing in on this subgroup.
Co-funded by the National Center for Complementary and Integrative Health; the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Institute of Environmental Health Sciences, the Trial to Assess Chelation Therapy 2 (TACT2) will examine the use of intravenous chelation (disodium EDTA) in combination with oral multivitamins in diabetic patients with a prior MI. The 1,200-patient randomized, double-blind study will test whether using chelation to “remove toxins from the blood” reduces the risk of recurrent all-cause mortality, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
Surprising everyone, the original TACT study, which wrapped up in 2012, found that acute MI survivors randomized to 40 separate 3-hour infusions of chelation—long deemed “alternative medicine”—along with a mixed vitamin regimen saw an 18% drop in risk of the trial's primary endpoint compared with patients randomized to a placebo infusion. In the prespecified secondary analysis presented at AHA 2013 and later published in Circulation: Cardiovascular Quality and Outcomes, investigators saw a much stronger effect in patients with diabetes—a 41% reduction in the risk of the primary composite endpoint, a 43% reduction in total mortality, and a 52% reduction in recurrent MI.
Strikingly, nondiabetic patients appeared to derive no benefit from chelation, suggesting that the improved outcomes in diabetic patients drove TACT’s overall positive results.
When TACT first came out, “the results were so unexpected. There was this innate initial flurry with everyone saying, it can’t be, we all know chelation is quackery,” Gervasio Lamas, MD (Mount Sinai Medical Center of Florida, Miami Beach), primary investigator for the original TACT trial, told TCTMD. “And people in the medical community rushed to judgement and said, ‘You must have done something wrong.’”
Lamas, who is study chair for TACT2, said he and his co-investigators “dug and dug” and were very open to having others review the data. At a certain point, “everyone realized we had a very unusual event on our hands, and that event was a completely unexpected result,” he observed. “Using a medication that allows increased excretion of lead and cadmium and other vasculotoxic metals reduced the risk of recurrent cardiovascular events. And when we looked at it a little more carefully in patients who had diabetes, which was about one-third of the TACT population, the effect was extraordinary.”
One theory that could explain chelation’s effects in diabetes may lie in the fact that advanced glycation end products, which mediate many of the complications of diabetes, appear to use metal-catalyzed oxidation for their formation. TACT investigators have previously speculated that removal of metal ions may be that much more important in diabetes subjects.
According to a press release issued by the TACT2 investigators today, they are currently recruiting participants for the trial, which will be conducted at over 100 sites in Canada and the United States. Subjects must be 50 years of age or older, have diabetes, and have had a previous MI.
The first trial struggled with slow enrollment and at one point was paused over concerns about the patient consent process. For TACT2, Lamas told TCTMD, enrolling sites have gone through a more rigorous screening process and will be primarily academic centers, cardiology clinics, and a smaller number of alternative medicine practitioners who demonstrated a commitment to best clinical trial practices in TACT—something that could not be said of all the original sites.
“There were a lot of lessons we learned in TACT 1 that don’t’ need to be relearned,” Lamas said.
TACT ultimately took 10 years to deliver results. Lamas hopes TACT 2 will wrap up in his “natural lifetime”—ideally, after the 5 years specified in the study design.
“Nobody was a friend of TACT in the beginning,” said Lamas. “But looking at the data in a dispassionate way is what it took to get the point where you can say, you know, the epidemiologists and other scientists tell us that these metals are associated with increased cardiovascular mortality, hypertension, MI, and stroke. Then you get a drug that’s safe, that takes this stuff out, why is it illogical to think that might work? And it really took us the investigators some time to really digest that, because it was so contrary to our biases.”
Principle investigators for the study are Kevin Anstrom, PhD, and Daniel Mark, MD (both of Duke Clinical Research Institute, Durham, NC).
Mount Sinai Medical Center. TACT2 clinical trial receives National Institutes of Health funding: Second study will focus on benefits of removing toxic metal pollutants in patients with diabetes and a prior heart attack. http://www.prnewswire.com/news-releases/tact2-clinical-trial-receives-national-institutes-of-health-funding-300334174.html. Published on: September 27, 2016. Accessed on: September 27, 2016.