Transcript Sample slide presentation on Chelation Therapy

TACT
Trial to Assess Chelation
Therapy
Principal Investigator
Gervasio A. Lamas, MD
Mt. Sinai Hospital; Miami Beach,
FL
TACT Sponsors and
Institutional Participants
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NIH—National Institutes of Health
– NCCAM—National Center for Complementary and
Alternative Medicine
– NHLBI—National Heart, Lung and Blood Institute
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Other Participating Institutions
– Duke Clinical Research Institute (Data
Coordinating Center and QOL Data
– Brigham and Women’s Hospital (Boston) Clinical
Events Committee
– Others
Basic Features of TACT
Study
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30 Million Dollar Study
Study to be conducted at approximately 100
Sites
Study to be conducted over a 5-year period
It is a randomized, double-blind, placebo
controlled study
Will test the value of chelation therapy and
high dose oral vitamins and minerals for
coronary artery disease
TACT Rockland County
Site
Schachter Center for Complementary
Medicine
2 Executive Boulevard; Suite 202
Suffern, NY 10901
Phone 845-368-4700; FAX 845-368-4727
Website: www.schachtercenter.com
E-Mail: [email protected]
TACT at the Schachter
Center
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Primary Investigator
– Michael B Schachter MD, CNS, FACAM
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Clinical Coordinator
– Sally Minniefield RN, PAC
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Assistant Clinical Coordinator
– Dolores Tritico RN
Specific Aims
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To determine whether chelation or
high-dose supplements in patients
with CHD will reduce the incidence of
clinical cardiovascular events;
To determine whether chelation and
high-dose supplements have
acceptable safety profiles.
Why is TACT Being Done?
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Raging controversy over the value of
chelation therapy for treating coronary
artery disease
More than a thousand physicians have used
chelation therapy to treat coronary artery
disease
It has been used for more than 40 years
Most of these physicians and the patients
receiving the treatment think that it is
effective
However, mainstream medicine regards it as
unproven and discourages patients from
receiving the treatment
NIH Wishes to Settle the
Controversy
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If chelation therapy safe and effective,
– then, many more should receive the treatment
– and insurance should cover the treatment
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If chelation therapy worthless,
– then, people with coronary artery disease should
stop wasting their time and money
– and insurance companies should continue to
refuse to pay
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Therefore, a well designed clinical study is
necessary
What is Coronary Artery
Disease?
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Most common form of heart disease
Arteries that carry oxygen and
nutrients to the heart get blocked with
plaque (fatty substances and calcium
salts)
Less oxygen and nutrients reach heart
muscle, leading to:
– Angina Pectoris-Pain in the chest
– Heart Attack or Myocardial Infarction
How Important is Coronary
Artery Disease (CAD)?
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Most frequent cause of death and
morbidity in the United States
7 million Americans suffer from CAD
More than 500,000 Americans die from
CAD each year
What are Risk Factors for
Coronary Artery Disease?
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High blood pressure
High cholesterol levels-Especially high LDL and low
HDL
Smoking
Obesity
Physical inactivity
Diabetes
Family history of CAD
Gender-Increased in men compared to
premenopausal women of comparable age
Age-Risk increases with age
How is Coronary Artery
Disease (CAD) Diagnosed?
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Symptoms-e.g chest pain on exertion,
shortness of breath
Blood tests that help to determine if a
heart attack has occurred
Electrocardiogram (may do with stress
test)
Echocardiogram
Imaging studies (e.g thallium scans
and angiograms)
How is Coronary Artery
Disease Treated in the
United States?
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Conventional treatment includes:
– Lifestyle modification (dietary changes and
exercise)
– Medication (ASA, Beta Blockers, ACE Inhibitors,
etc)
– Invasive interventions (Bypass, Balloon
angioplasty, Stents
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Despite these “proven” treatments, a
national survey reveals that 1/3 of patients
seek alternative therapies, including EDTA
chelation therapy
What is Chelation?
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Greek word chelos meaning claw
Refers to an organic molecule binding a
mineral tightly
Examples: chlorophyll is a chelate of
magnesium and hemoglobin is a chelate of
iron
EDTA is a synthetic amino acid capable of
binding to lead, cadmium and other toxic
metals, as well as calcium
Chelating Agents and
Chelation Therapy
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Many chelating agents
EDTA is a chelating agent approved by the
FDA to remove lead from the body
Chelation therapy involves administering a
chelating agent for the purpose of removing
a toxic mineral from the body
Removal of toxic minerals may help
coronary artery disease because there is
evidence that toxic minerals may play a role
in coronary artery disease
Brief History of EDTA
Chelation Therapy
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1950’s-EDTA found to be useful to treat lead
poisoning
Dr. Clark in the 1950’s reasoned that since EDTA is
also capable of binding calcium and calcium is
found in the clogged arteries in the plaque, perhaps
EDTA could be used to treat coronary artery disease
Initial clinical observations were very promising and
several papers were published supporting its use
Three small randomized placebo controlled studies
in recent years failed to show benefits
Controversy rages over whether or not it is
beneficial
Technique for EDTA Chelation
Therapy for CAD
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Disodium EDTA is a synthetic amino
acid
Chelates or binds heavy metals and
calcium
Intravenous infusion given for 3 hours
Administered in MD’s office once a
week, usually for 30 to 50 treatments
Magnesium, potassium, vitamins B6,
C, heparin and other components
added to infusion
EDTA Chelation Therapy for
CAD is Part of Full Program
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Part of a total program that involves
diet, supplements, exercise, stress
management and medication
Depletes trace minerals, so these must
be replaced with good diet, oral & IV
minerals
Side effects minimal when the ACAM
protocol is followed
Proposed Mechanisms for
How Chelation Therapy
Works
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Reduces free radicals
Removes toxic minerals, such as lead
and cadmium, which may contribute to
CAD
Removes soft tissue calcium
Others
Possible Side Effects of
Properly Given EDTA
Chelation Therapy
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Generally side effects are few and not serious
Most common is irritation at the site of infusion
Rare side effects can include:
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Fever
Low blood pressure
Low serum
Headache
Nausea and vomiting
Injury to the kidneys
Others, but extremely
Examples of Published
Studies Claiming Benefits
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Danish study
Brazilian study
Meta-analysis
Review article by Dr. Schachter
Reducing CV Surgical
Intervention With Mg-EDTA
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Retrospective Danish study involving 470 CV
patients involving many parameters
80—91% improved from baseline depending
on parameter used
Waiting list for CABG or amputation
58/65 did not need CABG after chelation
24/27 did not need amputation after
chelation
Hancke C & Flytlie K. Journal of Advancement in Medicine,
Vol. 6, Number 3, Fall 1993, 161-171.
EDTA For Heart, Peripheral
and Brain Circulation
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Brazilian retrospective study involving 2,870
patients with CV and other diseases
Objective criteria used
98% peripheral CV showed marked or good
93% coronary CV showed marked or good
60% cerebro CV showed marked or good
Olszewer, E & Carter JP. Medical Hypothesis, 27, 1988, 41-49.
Meta-analysis Of EDTA
Chelation For CV Disease
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Review of 19/40 articles involving 22,765
patients that met criteria to measure effects
of EDTA on CV disease
Correlation coefficient of 0.88 suggesting a
high positive relationship between EDTA
therapy and improved CV function
87% of patients improved
Chappell LT & Stahl JP. Journal of Advancement in
Medicine, Vol.6, No.3, Fall 1993, 139-159.
Review Article on EDTA
Chelation Therapy
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“Overview, historical background and
current status of EDTA chelation
therapy for atherosclerosis”
Reviews of scientific studies, clinical
reports
Analysis of controversies
Schachter MB, Journal of Advancement in
Medicine, Vol.9, No.3, Fall 1996, 159-177.
Criticism of Positive Articles
on Chelation Therapy
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Published in journal of organization that
promotes EDTA chelation therapy and
teaches it to physicians
All authors are strong proponents of
chelation therapy and may be biased
Studies not randomized, double-blind or
placebo controlled
For these and other reasons, most
conventional clinicians are skeptical and
think the treatment is at best unproven
NCCAM View of EDTA
Chelation Therapy Evidence
for CAD-1
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Bulk of the evidence supporting EDTA chelation
therapy is in the form of case reports and case
series.
Approximately 12 published descriptive studies and
5 randomized controlled clinical trials regarding the
use of EDTA chelation for CAD.
Although each descriptive study did report a
reduction in angina, they were uncontrolled clinical
observations or retrospective data, typically with a
small number of participants.
NCCAM View of EDTA
Chelation Therapy Evidence
for CAD-2
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Of the five clinical trials in which patients were
randomly selected to receive chelation therapy or a
placebo (a dummy solution), the most rigorous way
of assessing a new treatment, three trials involved
so few people that only a dramatic improvement
could have been detected. Studies need larger
number of participants to detect more mild benefits
of a treatment.
The fourth study was never published in final form,
so its conclusions are uncertain.
Finally, the fifth study reported that EDTA chelation
was associated with an improvement in ability to
exercise, but it had only 10 participants.
TACT’s Attempt to Settle the
Question
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Multicenter study involving as many as
100 sites or more
Some sites are run by chelation
proponents and others by conventional
cardiologists or other conventional
MDs, who are skeptical
Study is randomized, double-blind and
placebo controlled
TACT Design
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5-year randomized, double-blind, placebocontrolled;
2X2 factorial trial;
Testing the standard chelation solution
versus placebo;
Testing the effects of a high-dose
antioxidant vitamin and mineral
supplementation, versus placebo.
Specific Aims
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To determine whether chelation or
high-dose supplements in patients
with CHD will reduce the incidence of
clinical cardiovascular events;
To determine whether chelation and
high-dose supplements have
acceptable safety profiles.
Details of TACT Trial:
Factorial Design—Two Trials
in One
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Total number of patients 2,372
Half (1,186) get chelation and half get
placebo
Half of each group above (593) will get oral
high dose vitamin and mineral supplements
(6 pills) and half of each group will get oral
placebo that looks like high dose vitamin
and mineral
All participants will receive a single vitaminmineral pill containing: B6, Zinc,
Manganese, Copper and Chromium
Primary Endpoint
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Composite clinical endpoint
including:
– all cause mortality
– myocardial infarction
– stroke
– coronary revascularization
– hospitalization for angina
Secondary
Endpoints
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Composite serious irreversible vascular
events including: cardiovascular
death, or non-fatal MI or non-fatal
stroke.
Substudy Specific Aims
Two substudies will be conducted whose
specific aims are as follows:
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To determine whether chelation or
high-dose supplements improve
quality of life;
To conduct an economic analysis of
chelation therapy and high dose
supplements.
Quality of Life Endpoints
Baseline Questionnaire on every randomized patient
administered by the Site Coordinator
Follow-up Questionnaire on 1000 randomized
subset by DCRI telephone at 6, 12 and 24 months
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Cardiac physical functioning: Duke Activity Status Index
Psychological well-being: SF-36 MHI5
Angina symptoms from Seattle Angina Questionnaire
Patient utilities: EuroQoL
Analysis by intention to treat
Timeline
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First patient enrolled September 2003.
Enroll for 3 years.
Follow patients until August 2007.
Trial ends in November 2007.
Inclusion Criteria
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Men or women age
50 and older
MI >6 weeks prior
to randomization
TACT
Definition of MI
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Biomarkers + (symptoms or ECG changes)
OR
Imaging evidence of myocardial scar +
evidence of coronary disease on
angiography.
This requires PI involvement, especially the
decision that the CAD corresponds to an
imaged scar. Remember that the CCC is
always happy to help.
Major Exclusion Criteria-1
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Chelation within 5 years
Known allergy to any components of solutions
or vitamins (heparin may be omitted from the
infusion)
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Carotid or coronary revascularization within 6
months, or planned revascularization
Symptomatic HF, or HF hospitalization within 6
months
Major Exclusion Criteria-2
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Uncontrolled hypertension
(BP>160/100)
No venous access
Creatinine >2.0mg/dL
Baseline platelets <100,000
Cigarette smoking within 3 months
Study Interventions
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ACAM protocol EDTA chelation vs
placebo
High dose antioxidant vitamins and
minerals vs placebo
Chelation Solution
Chelation placebo solution is 500 ml 500cc of 0.9N NaCl, and 1.2% dextrose
Additive
Role of Additive
Up to 3 grams of disodium
EDTA
2 grams of magnesium
chloride
To reduce local discomfort and replace
losses
100 mg of procaine HCL
To reduce local discomfort
2500 units of heparin
To reduce local phlebitis
7 grams of ascorbate
Anti-oxidant and to achieve isoosmolarity
2 mEq KCl
To replace losses
840 mg sodium
bicarbonate
To act as a buffer and reduce discomfort
250mg pantothenic acid
For anti-oxidant properties
100mg of thiamine
For anti-oxidant properties
100mg of pyridoxine
To replace chelation losses
QS with sterile water to
500ml
Pharmacy – Delivery of
Study Drugs
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Infusion Kits – UPS delivery the morning
before scheduled visit
– 500 ml bag IV solution
– 2 - 20ml syringes
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Vitamins – Initial supply shipped with first
kit
– Subsequent shipments every two months
– Subsequent shipments contain 2-month supply
(360 tablets in a bottle; 60 gel-caps in blister
packs)
– After the completion of the 40th infusion,
shipments will be done on a quarterly basis.
Pharmacy – Simple
Mixing Instructions
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Prepare infusion just prior to
administration
Inject 2 syringes of solution into IV
bag using 21 g needles
Allow solution to reach room temp
prior to infusing (30 minutes)
Administer within 24 hrs of mixing
g Shipment
Blinding the Therapy
Non-Study
Interventions
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Up to date guidelines for medical
management of post-MI patients
including statins, aspirin, beta-blockers,
and ACE inhibitors.
Study Overview
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Screening and Randomization
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Perform initial screening
Obtain informed consent
Submit lab samples
Complete screening worksheet
Administer EQOL Baseline Questionnaire
Review lab results for eligibility
Randomize via TrialMaster
Study Overview
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Infusion Visits
– Initial - Weekly X 30 wks
– Maintenance - Every 2 – 8 weeks
– Enter data into TM during or
immediately post visit
Study Overview
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Patient Follow-up:
– 3 phone calls/year (average 2.5 years
f/u)
– 1 annual clinic visit
– Clinic visit at end of study
Why Should You Enroll in
TACT?
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No cost to anyone participating in the study (the cost for the
treatment for those receiving the active treatment would
probably be somewhere between $5,000 and $8,000)
Potential benefit if EDTA chelation beneficial
Potential benefit if high dose vitamins and minerals are
beneficial
Everyone gets low dose nutrient pill
75% chance of getting chelation, high dose vitamin mineral or
both
Altruistic-Contribute to knowledge about benefits of EDTA
chelation therapy
In general, subjects in a study are watched closely and
generally do better than patients not in a study