This March, the results of the Trial to Assess Chelation Therapy, which looked at the effects of chelation therapy on heart disease, came out in JAMA.
What is chelation therapy, you ask? It works like this: a substance that binds heavy metals is given to a patient in order to help him or her excrete these toxic substances. So let’s say that you find your child chewing on lead-containing paint chips. Your first stop should be the hospital, to start chelation therapy. Chelation therapy has also drawn a huge following in the alternative medicine community, though, where it’s thought that many ailments result from heavy metal toxicity. Some parents have been using chelation therapy on their autistic children, in the belief that autism is caused by exposure to mercury via vaccines or other sources. In 2005, a young boy actually died while receiving chelation therapy. Other patients have been using chelation therapy to treat things like heart disease.
The rationale for treating heart disease with chelation therapy is a little confusing. I don’t think anyone believe that a buildup of toxic metals is a primary cause of heart disease. But some proponents appear to believe that EDTA removes calcium from the plaques inside of blood vessels, causing them to shrink, OR that metal ions inside the body produce free radical damage to blood vessels. In the 1990s, trials found no evidence that chelation therapy worked for this purpose. But apparently some alternative health providers have been marketing as an alternative to invasive surgeries anyway, telling patients it will clear their arteries (I borrowed an example of this type of false advertising from Quackwatch–you can see it below).
TACT has been controversial since the moment it began. This trial cost over 30 million dollars and took over a decade to complete. How did a trial this mammoth get started when the previous literature provided little reason to think that chelation therapy would be successful? Well, a proposal for a chelation therapy was submitted to the National Heart, Lung, and Blood Institute in 2000. Not surprisingly, it was rejected. However, the American College for Advancement in Medicine (or ACAM, a pro-chelation organization) and U.S. representative Dan Burton (a proponent of the theory that vaccines cause autism) kept agitating for a chelation trial. And, as it happens, The National Center for Complementary and Alternative Medicine at the NIH issued a very specific call for applications in response. They asked for proposals to investigate the EDTA chelation treatment protocol recommended by ACAM. Not surprisingly, a proposal to do just this was approved, and the TACT study was born.
In TACT, roughly 1,700 patients were treated with 40 three-hour infusions of the chelator disodium EDTA over the course of a year. Not a trivial undertaking for the patients involved! More than half of the sites at which therapy was provided included alternative medicine centers that had been providing chelation for years. Two of them were suspended because of violations. In the middle of the trial, the guy who owned the pharmacy that supplied the EDTA for the trial was indicted for Medicaid fraud. Of the health providers administering the therapy, several were convicted felons, several more had been disciplined by their state medical boards, and still others had been involved in insurance fraud. In addition, one prominent pro-chelation author who admitted that he had falsified data was nonetheless cited a number of times in the TACT protocols. Enrollment for the trial was put on hold in 2008 for an investigation into complaints about things like the centers failing to obtain informed consent properly. And as if all that wasn’t enough, the NIH centers that sponsored the trial weren’t kept blind throughout, as is typical. Instead, they analyzed data periodically throughout the study. So even before the study was complete, it had its fair share of critics.
What did the study’s authors report in the end? Heart attack patients over 50 years of age who got chelation therapy had almost 20% fewer cardiovascular events (mortality, another heart attack, stroke, coronary revascularization, or being hospitalized for angina) than those given a placebo. Now 20% sounds pretty substantial, but the results only just made statistical significance, with a p-value of 0.035. Critics of the study pointed out that, in addition to the concerns listed above about how the study was carried out, it was odd that significantly more patients who received the placebo dropped out of the trial. This is the opposite of what you’d expect–since a treatment is usually associated with more side effects than the placebo, typically patients in the treatment arm drop out at a higher rate. If just a few patients had been treated differently–not hospitalized for angina, not subjected to coronary revascularization–the statistical significance in the study could have disappeared. So if the doctors responsible for these patients were not blinded to their treatment arm, and their knowledge affected the treatment they provided, this may have affected the study results.
So what should we take away from this 30 million dollar, 10 year study? Even if many cardiologists don’t believe chelation therapy resulted in a significant improvement in heart disease patients, and the positive result was spurious, given the popularity of the treatment, some seem relieved that at least it doesn’t seem as though chelation therapy is dangerous. I guess that is encouraging! Overall, though, this seems like a great example of why scientific proposals should be vetted by scientists, rather than being pushed through NIH by lobbyists and congresspeople. It’s not unusual for big, expensive clinical trials to end up with ambiguous results. But in this case, a ton of money and effort was lavished on a study with a very skimpy rationale and major methodological issues–one that couldn’t have gotten past the peer-review process without substantial help from outside. The recent meddling of congresspeople like Lamar Smith in the grant funding process doesn’t bode well for science.