When TACT began in 2002, Stephen Straus, MD, Director of the National Center for Complementary and Alternative Medicine (NCCAM), opined, “The public health imperative to undertake a definitive study of chelation therapy is clear. The widespread use of chelation therapy in lieu of established therapies, the lack of adequate prior research to verify its safety and effectiveness, and the overall impact of CAD convinced NIH that the time is right to launch this rigorous study.”4
TACT was the brainchild of Gervasio Lamas, MD, a Miami cardiologist and experienced NIH trialist since 1995. In 1999, a patient asked Dr. Lamas about undertaking chelation with a local alternative medicine practitioner. Dr. Lamas initially discouraged the patient but later realized there was no clinical trial information upon which to base his opinion, and TACT was soon born.
Practitioners of chelation therapy were delighted at the prospect of a large study underwritten by the U.S. government, but the community was not without reservations. Some seasoned chelation practitioners, harried by years of perceived persecution by the medical establishment, were wary of a trap and did not trust Dr. Lamas.
Others questioned whether it was wise to cooperate with Dr. Lamas in view of the fact that, with or without a big study, chelation was performed anyway, albeit with the disapproval of mainstream medicine. Why risk a negative outcome?
There was even concern that, should the trial be successful, the therapy might be co-opted by conventional cardiologists or adopted by Medicare and private insurers with strict caps on reimbursement.
Many raised concerns over the possibility that the study might not be robust enough statistically. Even with a hefty $31.6 million allocation from the NIH, could enough patients of the right type be recruited and treated adequately to capture and highlight—under artificial experimental conditions—the benefits of chelation therapy?
There were also methodological concerns over what endpoints would be measured. Would the study track such hard statistics as coronary deaths or cardiac events, or would more subtle markers based on changes in circulation (e.g. angiography, radionuclide stress tests, positron emission tomography scans, coronary artery calcium scoring) be needed to delineate subtle effects of chelation?
When determining the types of patients to be recruited for the trial, there was concern that the benefits of chelation might not be easily discerned if the participants were too healthy; patients who were very sick might be too far gone to experience disease reversal with chelation. In addition, ethical considerations would mandate that sick heart patients be correctly medically managed on a proper array of heart drugs, which might blunt the efficacy of chelation were it not applied as a standalone therapy.
The number of chelations each patient in the trial would undergo was another factor to be considered. Many individuals with advanced heart disease have succeeded with 60 to 100 or more chelations, but the practical dictates of a large-scale study argued for a more manageable number (i.e., 40). However, with such a low number of chelations, many proponents were worried that the treatment’s upside would not be sufficiently reflected.
A fair amount of debate also centered on how best to study chelation in isolation when the therapy is typically administered as the anchor of a transformational experience that includes lifestyle modification (healthful diet, adequate exercise, reduced stress) and a regimen of numerous vitamins and supplements.
The researchers had to determine how chelation therapy could be subjected to a double-blind, placebo-controlled study, the gold standard of scientific inquiry. The final hurdle was how to recruit a sufficient number of patients to participate in an arduous (albeit free) regimen of IV treatments knowing that there was a 50/50 chance of being infused with inactive colored water as part of the placebo group.
Dr. Lamas and his research team took great care to address these challenging questions. It was decided that the trial subjects be patients aged 50 years and older who had suffered an MI at least six weeks prior to the initiation of chelation.
Exclusion criteria included chronic renal failure (creatinine ≥2.0 mg/dL), liver disease, current smoking, or revascularization procedure within the past six months. Placebo and control arms alike were to be carefully managed with maximal medical therapy (i.e., anticoagulants, statins, beta blockers, and antihypertensive medications). In fact, 90% of the participants were on blood thinners, and 83% had undergone revascularization. With a median age of 65 years, the majority of the patients were obese (average BMI 30), and many had diabetes.2
Approximately half of the patients in TACT were recruited from alternative medicine practitioners and treated in their offices; the other half was treated at conventional medical centers. To solve the placebo conundrum, after randomization, active and placebo infusions were prepared offsite and delivered in blinded fashion to trial sites.
Extensive debate preceded the initiation of TACT with regard to whether trial participants should receive oral vitamins typical of chelation practice. Some trial designers were concerned that this would confuse the issue given the fact that previous studies assessing the merits of multivitamins in prevention of cardiovascular disease have yielded conflicting results (some even suggesting harm).
Chelation practitioners argued that giving vitamins with chelation more accurately reflects real-world chelation practice. Besides, it was argued, EDTA reacts with calcium, zinc, copper, and other micronutrients, thereby raising at least the theoretical specter of iatrogenic depletion if supplements are not included in the study.
The pro-multivitamin faction ultimately won out, resulting in a two-by-two factorial design: active chelation plus vitamins; active chelation plus placebo vitamins; placebo chelation plus vitamins; and placebo chelation plus placebo vitamins.
Opposition to TACT
Almost as soon as TACT had begun, critics of “unscientific” medicine harshly assailed the study. In 2008, a group authored an article that argued for the abandoning of TACT.5 The authors cited a variety of reasons for their opposition to the study and leveled accusations of conflict of interest and scientific impropriety against some of TACT’s investigators.
The article claimed that the inefficacy of chelation had already been sufficiently adjudicated by previous studies. The authors concluded that the trial posed unacceptable risk to its subjects and was a waste of money.
In a rebuttal that appeared in the Journal of American Physicians and Surgeons, Beth Clay, a former member of the U.S. House of Representatives, Committee on Government Reform, pointed out that the authors of the anti-TACT article “derive income from legal compensation for testifying against medical professionals who use chelation or other alternative or complementary therapies in their practices.”6 Ms. Clay also claimed that investigation of off-label uses of FDA-approved drugs is essential for progress in medicine.
TACT was beset by other problems as well. Enrollment proceeded slowly, and inadequate patient recruitment threatened to compromise the study’s statistical strength.
In 2003 and 2004, the deaths of two children were attributed to EDTA chelation, resulting in an unfavorable series of press reports highlighting the hazards of chelation.7 Defenders of the therapy argued that these tragedies resulted from dangerously rapid administration of disodium EDTA, which should be infused gradually over the course of three to four hours, as the TACT protocol dictated.
The low-water mark for TACT occurred in 2008 when the trial was temporarily halted after the Office for Human Research Protections of the U.S. Department Health and Human Services was persuaded by critics to launch an investigation. After nearly a one-year delay, the trial was exonerated and allowed to proceed.
Despite many obstacles, TACT was finally completed in 2011 and presented at the American Heart Association’s 2012 Scientific Sessions in Los Angeles.
This article originally appeared on Clinical Advisor