Cyclodextrin Coronary Calcium Score Reduction Pilot Study
Subject Description and Subject Consent and Agreement Form
Summary: Our study will assess the effect of Cyclodextrin on CAC (coronary artery calcification score) progression. CAC reflects the extent and chronicity of coronary atherosclerotic plaque. CAC progresses inexorably, with slow progression (< 15% per year) associated with favorable outcomes, with more rapid progression associated with increased coronary event risk. To this point, no therapy had been demonstrated to predictably stabilize or regress CAC. We will measure CAC and CAC progression rate in relation to a six-month program of Cyclodextrin.
Background: Over the past two years, well over 100 of our patients have received Cyclodextrin. Our observation is that ischemic symptoms (effort related chest pain or shortness of breath in patients with coronary disease and effort related leg pain in those with lower extremity atherosclerosis) begins to improve within 2-4 weeks, typically with symptom attenuation or full resolution at 2-3 months. We feel that Cyclodextrin works by pulling cholesterol (cell membrane, lipid droplet, and calcific) out of the artery wall, in a fashion that generates nitric oxide and attenuates vascular wall inflammation.
We feel that Cyclodextrin is safe. After reviewing the literature, and before our first patient began rectal Cyclodextrin, Dr. Roberts began a program of 6 gm IV Cyclodextrin infusions (a total of 50 over 3 months). Side effects reported by our patients relate to the Cyclodextrin delivery system (a small retention enema), and have been nuisance in nature (gas, cramping, diarrhea – intolerable in a limited number of you).
In symptomatic patients, dosing (treatment duration) is straightforward; Cyclodextrin is continued until your symptoms resolve, we tack on another month for safe measure, and follow this with maintenance therapy (1-3 doses per week or one month 1-3 times/year) in relation to your disease burden. What is not clear is how to best dose Cyclodextrin in asymptomatic patients. Here, blockages are not yet flow restrictive, such that if we open them further (a good thing) you will experience no symptomatic benefit.
What we are looking for, in our pilot study, is a measuring stick of Cyclodextrin efficacy with respect to atherosclerotic burden. We have observed carotid bulb plaque regression on our patient’s carotid artery intima-media thickness exams, but this is a specialized study, not available to the general public. Candidate measuring sticks include invasive angiography and non-invasive coronary artery CT angiography (possibly with its refinements, fractional flow reserve or Cleerly secondary analysis). The down sides here are relatively high cost along with procedural and radiation risk. Coronary calcium (CAC) scoring is readily available, inexpensive ($100), with lower (equivalent to ambient exposure over one year) radiation exposure. Thus, our pilot study will use CAC as a measuring stick of plaque burden.
Pilot study subjects will be characterized as:
a) Under the care of Dr. Roberts or Dr. Poling.
b) Free of serious non-cardiac or potentially life-threatening disease states.
c) With demonstrable coronary calcification.
d) Asymptomatic, or with stable symptoms, and without cardiac hospitalization or
revascularization over the preceding six months.
e) Willing and able to take Cyclodextrin over the planned six-month time frame, while
continuing your prior treatments (which will not be restricted, and which may be
adjusted in relation to your status).
f) Subjects with prior bypass surgery and stent placement may participate, but
we need at least one artery that does not bear a stent (which shows up as
calcification).
g) Subjects with prior Cyclodextrin therapy can participate.
Study logistics will involve:
a) You and Dr. Roberts or Dr. Poling will discuss the study, its goals, and our
reciprocal responsibilities.
b) You sign this consent and agreement form.
c) You complete one week of Cyclodextrin, which we provide (to make sure your
tolerance is OK). Cyclodextrin is administered as a small enema typically in the
late evening. The longer the material is kept in (ideally overnight) the better,
but three hours should be sufficient
d) A CAC will be obtained (we can provide you with a prescription but this is
not necessary). You pay for the scan out of pocket, give us the receipt, and we
will reimburse you within 2-4 weeks (but if you have undergone CAC within 3
months it can serve as the baseline).
e) You will receive a three-month supply of Cyclodextrin.
f) After 2 ½ months, you will contact us, and we will provide you with an
additional three boxes.
g) After you have completed six boxes, you will undergo a second CAC, at the
same site as your baseline study (to allow an apples-to-apples comparison) and
again we will reimburse you the cost.
h) If a patient has begun Cyclodextrin in relation to an abnormal CAC, they may
participate, with study supplied Cyclodextrin and a study covered CAC at the six
month point.
i) We understand that travel, intercurrent illness, or the need for a
non-cardiac procedure may force you to interrupt your Cyclodextrin program, and thus
the second CAC will not be at six months per say, but after you have utilized
six boxes of Cyclodextrin.
j) Your participating study physician will take note of your history,
treatments, and baseline lab studies, as well as any changes that occur during
your study participation. This will help us determine patient characteristics
or concomitant treatments that influence Cyclodextrin efficacy.
Fifty subjects will be included. We will reimburse you for the CAC, and the
sponsor will
reimburse us. Cyclodextrin will be provided to you free of charge. You will not
receive any financial compensation for your participation, nor will the
physician involved receive any fees. This is not an Institutional Review Board
(IRB) monitored study, registered with the FDA as a research protocol. This is
not necessary as CAC scans and Cyclodextrin can be accessed by you without a
prescription.
We feel that Cyclodextrin is the most important vascular therapy currently available, and that widespread adoption and availability of Cyclodextrin will save millions of lives and billions of dollars. We are hopeful that our findings will facilitate this process, while helping us determine optimal dosing, treatment duration, and synergizing therapies.
You can drop out of the study for any reason, and this will not preclude you remaining a patient.
I, ___________________, being of sound mind and not under the influence of drugs or alcohol, consent to participate in the Cyclodextrin CAC Pilot study, under the guidance of Dr. Roberts or Dr. Poling. The study and risks associated with Cyclodextrin and CAC scoring have been explained to me, and I have reviewed Dr. Roberts’s writeup and website (heartfixer.com) Cyclodextrin presentation. I understand that I will not be compensated in any way for my participation, which is purely voluntary, and which I can terminate at any time without repercussion.
_____________________ ___________________ _____________________
Name
Date Witness