Wednesday, July 9, 2008

From the "Really Bad Ideas" Vault

From this article in the Kansas City Star, I learned that the National Institute of Mental Health is considering a clinical trial of chelating agents as a potential treatment for autism. (When I searched NIMH's website, the only page I could find for such a study was from 2006. Since the newspaper article mentioned the proposed study was "on hold," and the basic plan sounds similar to that described in the article, and I could find no more recent announcement of a study like this, I suspect that the 2006 plan is being reactivated).

The NIH is also doing a parallel investigation of Na2EDTA chelation as a potential treatment for coronary artery disease, which has been denounced in Medscape and on the blog Health Care Renewal, to which one of the authors of the Medscape article contributes. There are some differences between the coronary-artery study (titled the Trial to Assess Chelation Therapy, or TACT) and the autism study: TACT is a Phase III clinical trial, while the autism study is a Phase II, and the chelating agent in the autism study is DMSA rather than Na2EDTA, but I think many of the problems Atwood et al found with TACT are still at work in the autism study, if not aggravated.

The main problem I see as being aggravated in the autism study is the problem of informed consent. Atwood et al claim that the TACT consent form omits crucial information on the risks of Na2EDTA chelation therapy, and makes no distinction between CaEDTA (which the FDA has approved to treat lead poisoning) and Na2EDTA (which the FDA has only approved for treating excessive calcium in the blood, and which is to be used with caution in patients with severe heart disease --- this latter would seem to make it an unwise choice for treating coronary artery disease, even if there were any reason to believe it worked).

Here's the FDA's own website on the two EDTAs, and the necessity of clearly distinguishing them:

There are two drugs approved by the FDA that have similar names are easily confused. To add to the confusion, both drugs are commonly referred to only as the abbreviation, "EDTA."

One drug is named "Calcium Disodium Versenate" and is also known by the chemical name of edetate calcium disodium. This drug is approved by the FDA to lower blood lead levels among patients with lead poisoning.

The other drug is marketed as "Endrate" and is also known by the chemical name of edetate disodium. This drug is approved by the FDA for use in selected patients with high blood calcium levels (hypercalcemia) as well as for use among patients with heart rhythm problems due to intoxication with the drug, digitalis.

The two EDTA drugs have different approved uses and significantly different effects. For example, edetate disodium is more likely to cause severe decreases in blood calcium levels. A severe decrease in blood calcium levels due to the erroneous administration of edetate disodium has resulted in death, predominantly among pediatric patients, who were to be treated for lead poisoning with edetate calcium disodium. As noted below, FDA has special concerns regarding the use of edetate disodium and is reconsidering the overall risks and benefits of the drug.

The consent form, however, did not mention any of this, referring to the reagent to be tested simply as "EDTA." The special risks of Na2EDTA, particularly those relevant to people with compromised heart health, were not brought to the attention of potential subjects.

Older patients with heart problems are not the only category of patient to have problems with Na2EDTA, either. These two articles give three case studies (both articles deal with the same three people) of patients (a 2-year-old girl with lead poisoning, a 5-year-old boy with autism, and a 53-year-old woman with no salient medical problems who was nevertheless being chelated by a naturopath) who died while undergoing chelation therapy. Hypocalcemia played a role in all of their deaths; the little girl suffered cardiac arrest, the woman had a fatal arrhythmia, and the boy's heart was found to be necrotic. (Calcium ions are used to regulate the pumping of the heart; if all the calcium in your blood is being bound up by chelators, it can't perform its regulatory function).

While DMSA is not as dangerous as Na2EDTA, it is also far from harmless. According to the FDA, there's a risk of neutropenia associated with DMSA and similar compounds:

Mild to moderate neutropenia has been observed in some patients receiving [DMSA]. While a causal relationship to [DMSA] has not been definitely established, neutropenia has been reported with other drugs in the same chemical class. A complete blood count with white blood cell differential and direct platelet counts should be obtained prior to and weekly during treatment with [DMSA].

The FDA also advises that people with impaired kidney function not take DMSA. So the risks here are that it's hard on the kidneys and may make you more prone to infection. It can also leach essential minerals (particularly zinc) from the body, although this effect is moderate in DMSA compared with other chelating agents.

Back to informed consent, this time with an eye to the specifics of the autism study. These patients are a lot more vulnerable than the patients in the TACT, as they are unable to advocate for themselves. The people who do advocate for them, their parents, are often so terrified by the prospect of raising a child with autism that they might think anything would be better than having their child remain autistic. This kind of desperation hardly makes for cool, rational risk-benefit analysis, the faculty for which is a critical part of giving informed consent.

The desperation factor would have to be heightened even above the baseline for autism among the parents of this study's participants, because DMSA and other chelating agents are supposed to remove toxic heavy metals that studies keep showing just aren't there. Chelation is also a pretty radical procedure: you're flooding your body with an all-purpose atom grabber that grabs and flushes from your system all metals, good and bad. At best, you've committed yourself to a regime of supplements and monitoring, and at worst, your bones, heart and immune system will suffer. Children are probably at special risk for growth or developmental problems caused by a lack of minerals. So this is a risky procedure that we have good reason to believe has no effect on the condition it's supposed to be treating in this study.


Anonymous said...
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Lindsay said...

My first spam comment. Oh joy.

Sharon McDaid said...

Nice post. I've just been googling to see what people are saying about this and opinion is split into predictable factions.

Have you seen the post at Pandagon?

Lindsay said...

Yeah, I did see the Pandagon post. I'm really glad Amanda wrote that, and I left a comment which was effectively a digest of this post there.