Chelation for CLI in Diabetic Patients Shows Potential in Small Series

HOLLYWOOD, FL—Patients with critical limb ischemia (CLI) on the backdrop of diabetes may get some relief from their leg and foot symptoms if toxic metals are removed from their body via chelation, according to early results from a small series presented yesterday at the 2019 International Symposium on Endovascular Therapy (ISET).

Gervasio A. Lamas, MD (Mount Sinai Medical Center, Miami Beach, FL), described this new application of chelation by showing before and after photos of several patients’ feet. Unhealed ulcers and toes black from gangrene were visibly improved following multiple infusions of disodium EDTA. “These are the kinds of pictures that have led me to believe that we need to look at this as an adjunct to [all peripheral vascular interventions],” he said.

Lamas acknowledged that chelation, in general, is often viewed as “quackery.”

In spite of this controversy, he has devoted many years to investigating the therapy’s potential, most famously in the TACT trial of post-MI patients. The study, published by JAMA in 2013, showed a “modest” reduction in adverse CV outcomes with an intravenous chelation regimen of disodium EDTA versus placebo. Results were most positive among patients with diabetes, leading to the 2016 launch of the ongoing TACT2 trial in this subgroup.

Speaking with TCTMD, Lamas suggested a “working hypothesis” as to why diabetic patients might be the target group in terms of benefit.

“Diabetics exist at a higher oxidative level because of their diabetes and all of the different cytokines that activates,” he said, explaining that, as part of their disease, the formation of advanced glycation end products is one root cause of atherosclerotic complications. Metals are a necessary ingredient involved in catalyzing that chemical process, so removing them might be helpful.

Chelation’s use in CAD patients first appeared in a published paper back in 1956, but somewhere along the way, it entered the territory of “alternative medicine” and got a bad rap, partly due to its association with less-experienced practitioners or other unconventional therapies, Lamas said.

Asked by TCTMD about the potential for chelation in PAD, Frank Veith, MD (Cleveland Clinic, OH), having seen Lamas’ talk, described himself as “skeptical but interested.” Most importantly, he said he looks forward to seeing how the results compare with those of controls, since in his experience sometimes patients’ feet can unexpectedly heal on their own.

What is Chelation?

Explaining the concept of chelation to ISET attendees, Lamas said the infused drug “has a pocket with an electrical charge, almost like a baseball mitt with a magnet in it. As with a mitt catching a baseball, the chelator will capture usually positive ions—toxic metals, for example, such as lead or cadmium—and hold onto them. The metals pass through the body and are excreted in the urine.”

The average person has small amounts of five to 10 toxic metals in his or her urine at any time due to environmental pollution, he continued. Giving an IV dose of disodium EDTA will increase the amount of lead released in the urine by nearly 40 times and the amount of cadmium by nearly seven times.

Physicians treating CLI tipped Lamas off to the idea that chelation might be effective in this subgroup, he said, so he decided to investigate further.

William A. Gray, MD (Lankenau Heart Institute, Wynnewood, PA), who moderated the session, said Lamas “has done an amazing job at putting [chelation] in a scientific framework.” One question he had following the presentation was: “Is there any downside effect of taking these metals out of the body?”

“You can take some essential metals out of the body, so we supplement those,” Lamas replied, adding, “I’ve never seen a credible case of a metal deficiency provoked by [chelation].” Anemia isn’t an issue, he said, because the amount of iron removed is “minuscule.”

The Outcomes

Also at ISET, Francisco Ujueta, MD (Mount Sinai Medical Center), presented a pilot study of chelation in 10 patients with diabetes and CLI, with Ivan A. Arenas, MD, PhD (Mount Sinai Medical Center), as lead author and Lamas as senior author. These individuals were given up to 50 infusions of disodium EDTA plus vitamin C, various B vitamins, magnesium, and other electrolytes over a 1-year period.

Cadmium and lead levels in the urine rose dramatically versus baseline with the first infusion and after later infusions. There were no treatment-related adverse events, and there were significant improvements in overall quality of life and in social limitation as ascertained by PAD questionnaire. SF-36 survey responses showed gains in physical function as well.

“These findings suggest that [these] infusions in diabetic CLI patients are safe, increase excretion of vasculotoxic metals, may improve quality of life, and might improve clinical outcomes,” Arenas and colleagues conclude. “This cautiously supports the design of a chelation trial in PAD.”

A total of 15 such patients have been treated so far, Lamas said, and he has just received funding for a study of 50 patients that will involve controls. Anticipating the study, he said, “it’s really hard to put these people in a control group and then see their legs wither. That’s going to be hard for me. So that’s why I’m hoping [this] small study is definitive enough so that it’s unethical to do a [larger one].”

Some of the intial patients are choosing to continue with monthly chelation infusions to keep their disease at bay, Lamas said. In terms of cost, he reported that it runs about $450 per infusion.