I had wanted to follow Dr. Sampson’s discussion of “Healing Touch” with one of my own, because I had an interesting experience with one of its proponents years ago, and I’ll do that soon. I had also wanted to begin a series of posts about acupuncture, which I’ll also do eventually. Just yesterday, however, Liz Woeckner, co-author of our recently published critique of the NIH Trial to Assess Chelation Therapy (TACT), made a startling discovery: the TACT “Portal” website, intended for investigators and others associated with the trial and previously password protected, is now available to anyone: http://www.chelationwatch.org/s/tact/index.html It is a goldmine of information and I’ve barely begun to look at it, but so far it verifies much of what we’ve written and more. For example, the latest version of the Consent Form is dated 2006 and includes this statement under “risks”:
EDTA, or ethylenediamine tetraacetate is in the chelation solution. It is approved for use by the FDA as a treatment for lead poisoning but not for coronary artery disease.
Yet three Investigator Brochures, dating back to 2003, contain this language:
Edetate disodium USP should not be confused with its calcium salt (calcium edetate), which is used to treat lead toxicity.
We had called attention, in our article, to TACT literature repeatedly conflating Na2EDTA and the safer CaNaEDTA. Now we have reason to believe that this has been done cynically, with eyes wide open.
Another example: the TACT newsletter of Mar ’04 is the “Special Advertising Edition.” On p. 3 is a “TACT spotlight interview with [Site Investigator] Dr. Sangeeta Shah.” The interviewer’s second question is: “Aside from the television interview, how did you advertise for this trial? What venues did you contact?” Part of her answer is:
Also, do not forget about advertising the trial on websites that a physician may have already have established. I have done this on my own website and if people are interested, they can visit the page at the following address: (here)
If you go to that link and click on “Chelation Therapy,” you’ll find much of the exact language that the FTC had compelled the ACAM (American College for Advancement in Medicine: the most conspicuous chelation advocacy organization) in 1998 to stop using in its advertisements for chelation:
WHAT IS CHELATION THERAPY?
Chelation Therapy is a safe, effective and relatively inexpensive treatment to restore blood flow in victims of Atherosclerosis without surgery. Patients with blockages and poor circulation in their hearts, extremities and other parts of their bodies often find relief without surgical intervention and heavy medication. Chelation Therapy involves the intravenous infusion of a prescription medicine called ethylene diamine tetra acetic acid (EDTA).
WHAT IS CHELATION THERAPY USED FOR?
Chelation Therapy is used to reverse symptoms of hardening of the arteries and blockages, also known as Atherosclerosis or Atherosclerosis. Atherosclerosis is caused by multiple complex factors, including abnormal accumulations of metallic elements. The end result is plaque formation within arteries, which blocks the flow of blood. Hardening of the arteries is caused by excess calcium building up in the walls of the arteries. Plaques are composed of fibrous tissue, cholesterol and calcium. Atherosclerosis leads to heart attack, stroke, and senility and may lead to amputation of extremities. Every single study of the use of Chelation Therapy for Atherosclerosis that has ever been published, without exception, has demonstrated an improvement in blood flow and symptoms. Adverse editorial comment to the contrary lacks evidence and stems primarily from physicians with a vested interest in catheterization and surgery. [etc.] [emphasis in the original]
Yet Federal Code prohibits investigators from promoting investigational drugs, as follows:
(a) Promotion of an investigational new drug. A sponsor or investigator, or any person acting on behalf of a sponsor or investigator, shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation or otherwise promote the drug.
In our article we had called attention to individual “Site Investigators,” including Dr. Shah, promoting chelation with sensational claims. Now we find that such promotion has itself been promoted by a newsletter emanating from TACT Central.
The tenor of the newsletters suggests that Dr. Lamas, the PI, thinks of his Chelation Site Investigators as immature, easily distracted schoolchildren. Hence the Sesame Street-like tone of “TACT Jeopardy” (TACTTALK Jan/Feb 06), “ALL THINGS BEING EQOL…” (TACT Tips Dec 05), “Congratulations TO THE WINNERS OF A CHOCOLATE GIFT BASKET FOR ENROLLING TWO PATIENTS IN OCTOBER 2005” (TACTTALK Dec 05), “Informed Consent – More than just a form” (TACTTALK March/April 2005), ” ‘Roadrunner Award’ for the swift completion of the regulatory requirements (Beep-Beep)” (TACTTALK Dec 04), “Hear ye, Hear ye… ALL TACT SITE INVESTIGATORS and COORDINATORS” (Flyer Apr 05) and many more.
The newsletters show that recruitment has been difficult and that many subjects have dropped out and are lost to follow-up. The treatment would seem to be neither as popular nor as pleasing as its promoters and TACT investigators have claimed, thus negating the NIH’s main justification for the trial. Or, perhaps, there’s another explanation: that, as was the case for the “Gonzalez Regimen,” most prospective subjects don’t want to take the chance of being in the control group. But that would only limit enrollment if chelationists were offering the treatment outside of the TACT. They are, of course, but probably not legally.
That might have something to do with why Dr. Rajiv Chandra of Melbourne, FL, is frequently cited as the “top enroller” for the trial. Chandra, as we explained in our article, promised this to prospective subjects:
If you participate in this study, you will receive 28 months of treatment, and be asked to participate in up to 32 months of follow-up. You will not be charged for participating in this exciting study and will receive the study drug and vitamin and mineral supplements.
Deaths
Reports of Serious Adverse Events (SAE) include two deaths. One occurred in a 74 yo man with critical aortic stenosis and moderately poor left ventricular function who was admitted to a hospital in florid congestive heart failure 6 days after his 32nd chelation infusion. In the other, a 59 yo woman with a history of congestive heart failure suffered an acute episode of left ventricular failure and pulmonary edema 14 hours after her 33rd chelation infusion, followed shortly by cardiac arrest. In each case “The investigator assessed the causal relationship between the study drug and the serious adverse event as not associated,” citing the subjects’ underlying diseases.
In the first case, however, during the subject’s most recent chelation infusion “the investigator [had] noticed evidence of gross lower extremity edema and administered an extra dose of Bumex 2 milligrams followed by as needed treatment.” There is no report that “as needed treatment” occurred, but the onset of signs of congestive heart failure in a subject with critical aortic stenosis constitutes a medical emergency. It is not grounds for an unmonitored extra dose of Bumex (a diuretic that can paradoxically worsen the circulatory problems associated with critical aortic stenosis).
The subject, moreover, may have been a better surgical than medical candidate (we can’t tell from the SAE report) precisely because of his critical aortic stenosis, for which most medical treatments are fraught with hazard. The man’s worsening renal function may have been due to his many Na2EDTA infusions, for which renal toxicity is a well-described outcome, the SAE report notwithstanding. Thus there may or may not have been a “causal relationship between the study drug and the serious adverse event,” but there is a strong likelihood that there was a causal relationship between the clinical incompetence of the Investigator and the demise of the subject.
According to the second case report, “pertinent laboratory information includes serum creatinine between 0.9- 1.0 mg/dL during the months of January through April of 2004, rising to 1.1-1.2 during May through July of 2004, 1.4 mg/dl in September of 2004, and 1.8 mg/dl on the day of her death.” This represents a progressive deterioration of renal function, again consistent with a known toxicity of Na2EDTA. In this case the proximity of the final infusion to the cardiac arrest, together with presenting signs and symptoms of “volume overload,” argue for a “causal relationship between the study drug and the serious adverse event.”
Even if the woman’s demise was merely a coincidence (also plausible, given her heart disease), her history of progressive renal insufficiency constitutes strong evidence that in this case, as in the previous one, the Site Investigator had dropped the ball. The Investigator did not even know that the woman had died until she failed to show up for her next chelation infusion, which, since she was in the “maintenance” phase, would have been scheduled several weeks later. Also disconcerting is this statement by the author of the SAE report:
We are distributing an investigator alert, since cardio-pulmonary arrest is not specifically mentioned in the TACT Investigator’s Brochure. We will keep you informed if further relevant information becomes available on this type of adverse event.
“This type of adverse event”? TACT investigators are purported to be experts in “chelation therapy,” a treatment with a rich history of this type of adverse event, and to “have substantial experience in the treatment and management of CAD,” a disease frequently associated with this type of adverse event. Does the reviewer of such Serious Adverse Events really think that TACT Investigators ought to be surprised by them, and need “further relevant information”?
These reports, I am more than angry to say, fulfill an implicit prediction that we made in our article:
The NIH has hired nearly 100 unqualified co-investigators to care for nearly 2000 unsuspecting subjects. In announcing the TACT, the late NCCAM Director Stephen Straus tacitly acknowledged that such soon-to-be co-investigators had been pushing chelation “in lieu of established treatments.” The TACT consent form warns subjects to “continue to use proven standard medicines for heart attack patients,” but the Declaration of Helsinki expects better:
Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent.
It is the obligation of investigators to provide reasonable predictions of efficacy and assurances of safety, on the basis of all “relevant sources of information,” prior to exposing human subjects to a phase 3 trial. The TACT investigators did not do that.
Your government at work.