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Chelation Therapy Trials Halted

Chelation Therapy Trials Halted The federal government and investigators have called off or suspended enrollment for 2 clinical trials testing chelation therapy as a treatment for autism or coronary artery disease. Critics charged that the studies had little scientific merit and exposed participants to unacceptable safety risks. The US Food and Drug Administration has approved chelating agents, which bind and remove heavy metals from the body, for treating acute toxicity of heavy metals. But, according to the National Center for Complimentary and Alternative Medicine (NCCAM), off-label uses of chelating agents contribute to an estimated 800 000 physician visits annually. Advocates argue that the approach is beneficial for autism and coronary artery disease, despite the absence of evidence from rigorous clinical trials. With the goal of clarifying whether chelation offers benefits beyond its indications for acute heavy metal toxicity, the National Institutes of Health (NIH) decided to fund 2 randomized controlled trials: the Trial to Assess Chelation Therapy (TACT), to evaluate the approach's safety and efficacy in reducing the risk of coronary artery disease, and the Mercury Chelation to Treat Autism study. However, on September 17, the National Institute of Mental Health (NIMH) announced the cancellation of the autism study. A week later, investigators running TACT, sponsored by the NCCAM and the National Heart, Lung, and Blood Institute, suspended enrollment as allegations of improper consent forms were evaluated. However, the 5-year trial would continue with those already enrolled. The mercury chelation study was intended to test a theory—embraced by some antivaccine activists but rejected by most scientists—that a vaccine preservative containing mercury (no longer in use) can cause autism, and that removing mercury from the body would improve social reciprocity and language skills in children with autism. In the trial, 120 children with autism spectrum disorder and detectable (but not toxic) blood levels of mercury or lead were to receive a chelating agent (succimer) or placebo. But a rodent study released online in late 2006 found that while chelation with succimer (the agent to be studied in the Mercury Chelation to Treat Autism study) improved learning, attention, and arousal regulation in lead-exposed animals, it also produced indications of lasting cognitive impairment (Stangle DE et al. Environ Health Perspect. 2007;115[2]:201-209). This study initiated a reassessment by an NIH institutional review board that ultimately redetermined that evidence for direct benefit to study participants was lacking while more than minimal risk was present. “This publication cast some doubt, and with the marginal increase of risk along with our marginal confidence that [chelation therapy] would make a difference, it seemed prudent to stop the trial,” said Richard Nakamura, PhD, NIHM's Division of Intramural Research Program's scientific director. The other trial, TACT, was similarly rooted in a hypothesis that critics deemed as lacking in support. Back in the 1950s, some researchers believed disodium ethylenediaminetetraacetic acid (EDTA) chelation could remove calcium from atheromatous plaque and reduce the risk for coronary artery disease, although subsequent studies could not find benefit through this mechanism. The TACT investigators hypothesized that EDTA would reduce oxidative stress in the vascular wall, leading to improved vascular function and a reduction in inflammation and cardiovascular disease events. To test this, the investigators launched a $30 million randomized trial, which involved giving disodium EDTA chelation or placebo to about 1950 individuals aged 50 years or older who had experienced a myocardial infarction at least 6 weeks prior to the study's start. But Kimball C. Atwood IV, MD, an anesthesiologist at Newton-Wellesley Hospital in Newton, Mass, and colleagues said the TACT trial is “unethical, dangerous, pointless, and wasteful” and that it should be abandoned (Atwood KC et al. Medscape J Med. 2008;10[5]:115). Atwood said enrollment stopped in TACT following his team's request to the US Department of Health and Human Service's Office for Human Research Protections for such an action due to misrepresentations found on enrollment consent forms. “TACT doesn't mention death risks in its protocols and consent forms, and it conflates disodium EDTA with another drug, calcium disodium EDTA,” Atwood said. Safety concerns led to disodium EDTA being pulled from the market in June. The lead TACT investigator did not respond to a request for comment. Atwood said chelation therapy appeals to patients desperate to find effective treatments who dismiss scientific evidence that chelation does not work except for heavy metal toxicity. “We have $30 million of public money and about 2000 subjects being duped by a misrepresentative consent form—some of whom will be injured,” Atwood said. “And the trial won't prove anything.” http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Chelation Therapy Trials Halted

JAMA , Volume 300 (19) – Nov 19, 2008

Chelation Therapy Trials Halted

Abstract

The federal government and investigators have called off or suspended enrollment for 2 clinical trials testing chelation therapy as a treatment for autism or coronary artery disease. Critics charged that the studies had little scientific merit and exposed participants to unacceptable safety risks. The US Food and Drug Administration has approved chelating agents, which bind and remove heavy metals from the body, for treating acute toxicity of heavy metals. But, according to the National...
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Publisher
American Medical Association
Copyright
Copyright © 2008 American Medical Association. All Rights Reserved.
ISSN
0098-7484
eISSN
1538-3598
DOI
10.1001/jama.2008.607
Publisher site
See Article on Publisher Site

Abstract

The federal government and investigators have called off or suspended enrollment for 2 clinical trials testing chelation therapy as a treatment for autism or coronary artery disease. Critics charged that the studies had little scientific merit and exposed participants to unacceptable safety risks. The US Food and Drug Administration has approved chelating agents, which bind and remove heavy metals from the body, for treating acute toxicity of heavy metals. But, according to the National Center for Complimentary and Alternative Medicine (NCCAM), off-label uses of chelating agents contribute to an estimated 800 000 physician visits annually. Advocates argue that the approach is beneficial for autism and coronary artery disease, despite the absence of evidence from rigorous clinical trials. With the goal of clarifying whether chelation offers benefits beyond its indications for acute heavy metal toxicity, the National Institutes of Health (NIH) decided to fund 2 randomized controlled trials: the Trial to Assess Chelation Therapy (TACT), to evaluate the approach's safety and efficacy in reducing the risk of coronary artery disease, and the Mercury Chelation to Treat Autism study. However, on September 17, the National Institute of Mental Health (NIMH) announced the cancellation of the autism study. A week later, investigators running TACT, sponsored by the NCCAM and the National Heart, Lung, and Blood Institute, suspended enrollment as allegations of improper consent forms were evaluated. However, the 5-year trial would continue with those already enrolled. The mercury chelation study was intended to test a theory—embraced by some antivaccine activists but rejected by most scientists—that a vaccine preservative containing mercury (no longer in use) can cause autism, and that removing mercury from the body would improve social reciprocity and language skills in children with autism. In the trial, 120 children with autism spectrum disorder and detectable (but not toxic) blood levels of mercury or lead were to receive a chelating agent (succimer) or placebo. But a rodent study released online in late 2006 found that while chelation with succimer (the agent to be studied in the Mercury Chelation to Treat Autism study) improved learning, attention, and arousal regulation in lead-exposed animals, it also produced indications of lasting cognitive impairment (Stangle DE et al. Environ Health Perspect. 2007;115[2]:201-209). This study initiated a reassessment by an NIH institutional review board that ultimately redetermined that evidence for direct benefit to study participants was lacking while more than minimal risk was present. “This publication cast some doubt, and with the marginal increase of risk along with our marginal confidence that [chelation therapy] would make a difference, it seemed prudent to stop the trial,” said Richard Nakamura, PhD, NIHM's Division of Intramural Research Program's scientific director. The other trial, TACT, was similarly rooted in a hypothesis that critics deemed as lacking in support. Back in the 1950s, some researchers believed disodium ethylenediaminetetraacetic acid (EDTA) chelation could remove calcium from atheromatous plaque and reduce the risk for coronary artery disease, although subsequent studies could not find benefit through this mechanism. The TACT investigators hypothesized that EDTA would reduce oxidative stress in the vascular wall, leading to improved vascular function and a reduction in inflammation and cardiovascular disease events. To test this, the investigators launched a $30 million randomized trial, which involved giving disodium EDTA chelation or placebo to about 1950 individuals aged 50 years or older who had experienced a myocardial infarction at least 6 weeks prior to the study's start. But Kimball C. Atwood IV, MD, an anesthesiologist at Newton-Wellesley Hospital in Newton, Mass, and colleagues said the TACT trial is “unethical, dangerous, pointless, and wasteful” and that it should be abandoned (Atwood KC et al. Medscape J Med. 2008;10[5]:115). Atwood said enrollment stopped in TACT following his team's request to the US Department of Health and Human Service's Office for Human Research Protections for such an action due to misrepresentations found on enrollment consent forms. “TACT doesn't mention death risks in its protocols and consent forms, and it conflates disodium EDTA with another drug, calcium disodium EDTA,” Atwood said. Safety concerns led to disodium EDTA being pulled from the market in June. The lead TACT investigator did not respond to a request for comment. Atwood said chelation therapy appeals to patients desperate to find effective treatments who dismiss scientific evidence that chelation does not work except for heavy metal toxicity. “We have $30 million of public money and about 2000 subjects being duped by a misrepresentative consent form—some of whom will be injured,” Atwood said. “And the trial won't prove anything.”

Journal

JAMAAmerican Medical Association

Published: Nov 19, 2008

Keywords: chelation therapy

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